Dengue Fever - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

DENGUE FEVER A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES ...

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DENGUE FEVER A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Dengue Fever: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83877-1 1. Dengue Fever-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on dengue fever. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON DENGUE FEVER ......................................................................................... 3 Overview........................................................................................................................................ 3 Federally Funded Research on Dengue Fever ................................................................................ 3 E-Journals: PubMed Central ....................................................................................................... 25 The National Library of Medicine: PubMed ................................................................................ 32 CHAPTER 2. NUTRITION AND DENGUE FEVER ............................................................................... 63 Overview...................................................................................................................................... 63 Finding Nutrition Studies on Dengue Fever............................................................................... 63 Federal Resources on Nutrition ................................................................................................... 65 Additional Web Resources ........................................................................................................... 66 CHAPTER 3. ALTERNATIVE MEDICINE AND DENGUE FEVER ......................................................... 67 Overview...................................................................................................................................... 67 National Center for Complementary and Alternative Medicine.................................................. 67 Additional Web Resources ........................................................................................................... 69 General References ....................................................................................................................... 69 CHAPTER 4. DISSERTATIONS ON DENGUE FEVER ........................................................................... 71 Overview...................................................................................................................................... 71 Dissertations on Dengue Fever.................................................................................................... 71 Keeping Current .......................................................................................................................... 72 CHAPTER 5. PATENTS ON DENGUE FEVER ..................................................................................... 73 Overview...................................................................................................................................... 73 Patents on Dengue Fever ............................................................................................................. 73 Patent Applications on Dengue Fever ......................................................................................... 85 Keeping Current .......................................................................................................................... 87 CHAPTER 6. BOOKS ON DENGUE FEVER ......................................................................................... 89 Overview...................................................................................................................................... 89 Book Summaries: Federal Agencies.............................................................................................. 89 Book Summaries: Online Booksellers........................................................................................... 90 The National Library of Medicine Book Index ............................................................................. 90 Chapters on Dengue Fever........................................................................................................... 92 CHAPTER 7. MULTIMEDIA ON DENGUE FEVER .............................................................................. 93 Overview...................................................................................................................................... 93 Bibliography: Multimedia on Dengue Fever................................................................................ 93 CHAPTER 8. PERIODICALS AND NEWS ON DENGUE FEVER ........................................................... 95 Overview...................................................................................................................................... 95 News Services and Press Releases................................................................................................ 95 Academic Periodicals covering Dengue Fever ........................................................................... 100 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 101 Overview.................................................................................................................................... 101 U.S. Pharmacopeia..................................................................................................................... 101 Commercial Databases ............................................................................................................... 102 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 105 Overview.................................................................................................................................... 105 NIH Guidelines.......................................................................................................................... 105 NIH Databases........................................................................................................................... 107 Other Commercial Databases..................................................................................................... 109 APPENDIX B. PATIENT RESOURCES ............................................................................................... 111 Overview.................................................................................................................................... 111 Patient Guideline Sources.......................................................................................................... 111 Finding Associations.................................................................................................................. 114

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APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 117 Overview.................................................................................................................................... 117 Preparation................................................................................................................................. 117 Finding a Local Medical Library................................................................................................ 117 Medical Libraries in the U.S. and Canada ................................................................................. 117 ONLINE GLOSSARIES................................................................................................................ 123 Online Dictionary Directories ................................................................................................... 126 DENGUE FEVER DICTIONARY ............................................................................................... 127 INDEX .............................................................................................................................................. 167

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with dengue fever is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about dengue fever, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to dengue fever, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on dengue fever. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to dengue fever, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on dengue fever. The Editors

1

From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON DENGUE FEVER Overview In this chapter, we will show you how to locate peer-reviewed references and studies on dengue fever.

Federally Funded Research on Dengue Fever The U.S. Government supports a variety of research studies relating to dengue fever. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to dengue fever. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore dengue fever. The following is typical of the type of information found when searching the CRISP database for dengue fever: •

Project Title: A MOUSE MODEL TO STUDY IMMUNE RESPONSES TO DENGUE VIRUS Principal Investigator & Institution: Shresta, Sujan; Infectious Diseases; University of California Berkeley Berkeley, Ca 94720 Timing: Fiscal Year 2002; Project Start 03-MAY-2002

2

Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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Summary: (provided by applicant): Dengue virus (DV) causes dengue fever (DF) and dengue hemorrhagic fever/dengue shock Syndrome (DHF/DSS), the most prevalent arthropod-borne viral illness in humans worldwide. Both clinical and in vitro laboratory studies have implicated immune-based mechanisms for the manifestations of DHF. Due to the lack of an adequate animal model for DV infection, the immunopathogenic mechanisms of DHF are not yet fully elucidated. As a first step towards understanding the role of the immune system in DV infection in vivo. this proposal aims to optimize a mouse model for DV infection by systematically evaluating novel routes of infection, different viral and mouse strains, and co-injection of immunomodulatory compounds (Specific Aim 1). Since the chemokine network is important in orchestrating anti-viral immune responses and evidence supports a role for chemokines in the immunopathogenesis of DHF, we hypothesize that chemokines (particularly CCL5) participate in the clearance of virus in mice challenged with DV. Thus, Specific Aim 2 is to define the in vivo expression pattern and function of CCL5 in mice with primary DV infections. The long-term goal of this work is to examine the contribution of chemokines to the immunopathogenesis of DHF in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: A NOVEL ADENOVIRUS-BASED TETRAVALENT DENGUE VACCINE Principal Investigator & Institution: Deitz, Stephen B.; Genphar, Inc. 871 Lowcountry Blvd Mount Pleasant, Sc Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JAN-2003 Summary: (provided by applicant): The deliberate attempts to infect political figures and high profile members of the 'the media' with anthrax after the attacks of Sept. 11, 2001 highlight the need for an effective strategy to deal with bioterrorism. The threat of bioterrorism is no longer just a threat. There are a large number of disease-causing agents that have the potential to be used as weapons and we must be prepared to neutralize their effectiveness whether they are ultimately used or not. For many potential bioweapons, the best defense is preemptive vaccination. Unfortunately, there are more disease-causing agents than there are vaccines. We have chosen to focus our attention on one potential bioweapon: dengue virus. Dengue fever and dengue hemorrhagic fever are incapacitating, potentially lethal diseases that are caused by dengue virus infection. Dengue infection has been problematic for American military personnel stationed in tropical or subtropical countries and there is some concern that the virus could be weaponized in the future. There are four common serotypes of dengue virus and immunity against one serotype can enhance the severity of disease following infection with another serotype. Therefore, an effective dengue virus vaccine must elicit a broad response that is capable of neutralizing all four serotypes. We will use a unique adenovirus-based expression system to create a novel tetravalent dengue virus vaccine. Phase I of this project will focus on subcloning genes from all four dengue virus serotypes into adenovirus vectors and characterizing the vectors with respect to protein expression. Three dengue virus genes, prM, E, and NS1, from each serotype will be inserted into adenovirus vectors. Expression of the dengue virus genes from the adenovirus vectors is expected to elicit both humoral and cellular immune responses. The first generation vaccine will consist of a mixture of two adenovirus vectors - each vector expressing six genes from two dengue virus serotypes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

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Project Title: A VIRAL VECTOR FOR GENE EXPRESSION IN INSECTS Principal Investigator & Institution: Dasgupta, Ranjit K.; Animal Hlth & Biomedical Scis; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-DEC-2005 Summary: More than 500 million people per year are adversely affected by mosquitoborne diseases such as malaria, lymphatic filariasis and dengue fever. Understanding the physiology of insect vectors, and the molecular interactions between those insects and the pathogens they transmit is critical for controlling these diseases. Viruses, such as Sindbis virus, developed for transient gene expression and gene silencing in insects have proven useful in this type of research. However, the few virus vectors available for this purpose are constrained by narrow host ranges, limited tissue dissemination, inability to express larger genes and human pathogenicity. Our goal is to overcome these problems and develop a highly efficient viral vector system based on a simple RNA virus called Flock House virus (FHV). The virus is a member of the Nodaviridae family of insect viruses. The adaptability of this virus to different hosts, its simple genome organization and non-pathogenecity to humans make FHV an attractive virus for vector development. The 4.5 kb genome of FHV consists of two positive sense single stranded RNAs, which are packaged into a coat protein with no envelope. Although of insect origin, FHV can overcome the kingdom barrier and replicate in plants and yeast. FHV has not previously been shown to multiply in mosquitoes and other insect disease vectors. We have demonstrated that FHV replicates in vitro in cultured mosquito cells as well as in vivo in four mosquito genera, Aedes, Cu/ex, Anopheles and Armigeres. We have expressed the reporter gene GFP in Drosophila ceils and in mosquitoes using FHV vectors generated in this laboratory. We have also shown that FHV replicates vigorously in tsetse flies. We will optimize existing, and develop new FHV vectors to extend its ability to infect medically important insects and express genes of interest. Specifically, we will (1) determine optimum conditions for the growth (both in vitro and in vivo) of FHV in mosquitoes and other insects that transmit diseases including tsetse flies, sand flies and kissing bugs (2) improve the existing FHV-based vectors so that they are capable of expressing or silencing one or multiples gene(s) in insects, and (3) silence two genes that belong to the family of serine proteases from the human malaria vector Anopheles gambiae, and assess their role in melanization. We expect that FHV vectors will be valuable tools for introducing or silencing genes in vivo in medically important insects in order to elucidate the function of genes with various physiological roles. These molecular tools will become increasingly more important as whole organism genome sequencing efforts rapidly progress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: BLOCKING DENGUE TRANSMISSION BY TRANSGENIC AEDES AEGYPTI Principal Investigator & Institution: Olson, Ken E.; Microbiology, Immunology & Pathology; Colorado State University Fort Collins, Co 80523 Timing: Fiscal Year 2001; Project Start 01-JAN-2001; Project End 31-DEC-2005 Summary: Dengue (DEN) and dengue hemorrhagic fever (DHF) have emerged as the most important mosquito-borne viral diseases affecting humans. DEN disease control is difficult because traditional vector control measures are becoming less effective and vaccines are not currently available. The molecular genetic manipulation of vector mosquitoes has been proposed as an approach to disrupt the transmission of DEN viruses and control DEN disease. The laboratory group at the Arthropod-borne and

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Infectious Diseases Laboratory (AIDL; Colorado State University (CSU), Fort Collins, CO) using transient alphavirus expression systems has identified gene-based, virusspecific, effector RNAs that profoundly alter the vector competence of Aedes aegypti for transmission of DEN viruses. The James laboratory (University of California, Irvine, CA) has developed methods for producing transformed mosquitoes using two different class 11 transposable elements, Hermes and mariner. Thus, for the first time, all of the components are in place to produce virus-resistant, stable lines of mosquitoes in the laboratory. Genetic analyses will be required to study gene flow of resistant-gene bearing transposons and determine if resistant genes will move through caged populations of mosquito vectors. The research program we propose has the following specific aims: 1) genetically-alter the vector mosquito, Aedes aegypti, with nonautonomous class 11 transposable elements to express anti-DEN effector genes; 2) evaluate the level of resistance and transmission-blocking potential of transgenic mosquito lines to all four serotypes of DEN viruses and among genetic variants of the viruses; and 3) evaluate the mobility and stability of anti-DEN genes as they are carried by autonomous transposable elements through cage populations of mosquitoes. Information derived in these studies may provide a new paradigm for control of vector borne diseases by interrupting the cycle of transmission at the level of the vector, which may then be directly applicable to other vector-pathogen systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGENS

CELLULAR

IMMUNE

RESPONSE

OF

MOSQUITOES

TO

Principal Investigator & Institution: Hillyer, Julian F.; Animal Hlth & Biomedical Scis; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-SEP-2001 Summary: (provided by the applicant): Mosquitoes are currently the most important arthropod vectors, transmitting a broad range of diseases such as malaria, lymphatic filariasis and dengue fever. A method for curtailing disease transmission is through vector control programs. It has been shown that mosquitoes are able to mount powerful cellular and humoral responses against invading pathogens, and that this response is directly correlated to vector competence. To date, most studies addressing mosquito immunity have focused on the humoral response. However, it is clear that hemocytes (mosquito blood cells) play a central role in the production of many of the players involved in the humoral response. The current study will address the role hemocytes from two immunologically different mosquito species, Aedes egypti and Armigeres subalbatus, have in the immune response mounted against prokaryotic, protozoan and metazoan parasites. This research will focus on 1) classifying the hemocytes, 2) studying the phagocytic response of hemocytes towards pathogens, 3) determining which cells are responsible for the transcription of immune molecules, and 4) determining the structure/function relationship between invading pathogens, hemocytes and soluble immune molecules. In understanding the immune response mounted by different insect species and strains toward pathogens, it may be possible to manipulate existing vectors to make the parasite/vector biologic interplay incompatible. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHIMERIC YELLOW FEVER 17D/DENGUE VACCINES Principal Investigator & Institution: Monath, Thomas P.; Vice President; Acambis, Inc. 38 Sidney St, 4Th Fl Cambridge, Ma 02139

Studies

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Timing: Fiscal Year 2000; Project Start 30-SEP-2000; Project End 31-MAR-2004 Summary: The aim of this proposal is to develop genetically engineered live, attenuated vaccines against Dengue types l4. The technology (Chimeri Vax TM) involves creation of chimeric viruses in which the envelope genes of the vaccine target virus (dengue) containing all the epitopes for neutralizing antibodies as well as protective CTL determinants are substituted for the corresponding genes of Yellow Fever (YF) l7D vaccine virus. The resulting chimera is a live vaccine, which, like YF 17D, elicits strong humoral and cellular immunity, but is antigenically specific for the heterologous virus. Wild type dengue strains will be used as gene donors, and the chimeric YF/dengue vaccine candidates will have an acceptable safety profile in animal models. Safety, immunogenicity and protective activity of all vaccine candidates will be established in non-human primates. A monovalent YF/dengue-2 vaccine candidate will first be prepared at clinical grade, and a proof-of-principle Phase 1 trial performed under IND to demonstrate validity of the approach in humans. Optimized YF/dengue-1, -3, and -4 vaccine candidates will be developed, tested in monkeys, and manufactured under GMP. A tetravalent YF/dengue vaccine will be formulated, dose composition determined by preclinical studies in monkeys, and an IND will be submitted for a Phase l clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHITIN BIOSYNTHESIS AND THE MOSQUITO PERITROPHIC MATRIX Principal Investigator & Institution: Christensen, Bruce M.; Professor; Animal Hlth & Biomedical Scis; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 30-NOV-2002 Summary: Mosquito-born pathogens continue to have a major impact on the health of human populations throughout the world, and malaria and dengue fever are considered two of our most important reemerging diseases. All pathogens transmitted by mosquitos are ingested with the blood meal and consequently they must survive within the mig-gut environment and be able to penetrate the peritrophic matrix and mid-gut epithelium to reach their site of development. Despite the importance of the midgut as a determinant for vector competence, little specific information is available regarding the genetic regulation of critical physiological processes that occur within the midgut following blood feeding. One of these processes is the formation of the peritrophic matrix (PM) that surrounds the blood bolus nd physically separates it from the midgut epithelium. We have cloned a full- length cDNA for Aedes aegypti glutamine synthetase (GS) and determined that it is mid-gut specific and induced by blood feeding. Our hypothesis is that GS is critical for chitin synthesis in PM formation y providing the glutamine necessary for the glutamine necessary for the glutamine: fructose-6-phosphate aminotransferase (GFAT) catalyzed production of glucosamine-6phosphate. Enzyme assay analyses also indicate that GFAT and chitin synthase (CS) play regulatory and critical roles in this biochemical process. Because very little is known concerning the biosynthetic pathway involved in PM chitin formation, or on the genetic regulation of this pathway, we propose herein biochemical and molecular studies of GS, GFAT, and CS that should provide a cleared understanding of this process. Specifically, we will (a) obtain DNA clones for GS, GFAT, and CS, and nucleotide and putative translation production sequences will be compared with those from other organisms, (2) use cDNA clones of these three enzymes to assess timing and location of transcriptional activity, using northern analysis and in situ hybridization,

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and to obtain recombinant proteins for antibody production and subsequent immunolocalization and enzyme inhibition studies, and (3) map and sequence the genomic structures for GS, GFAT and CS in order to identify and characterize those mechanisms regulating gene expression. We will use a number of techniques including extensive studies of promoter sequences, transgene mosquitos, electrophoresis mobility shift assay, DNase I footprinting, and physiological studies to evaluate potential promoter and enhancer sequences. None of these genes has been isolated from mosquitos and we anticipate satisfying our specific aims will provide us with a much clearer understanding of chitin synthesis associated with PM formation. A more complete understanding of biochemical events operating in the mid-gut following blood feeding also as the potential of providing new approaches for disrupting pathogen transmission. Likewise, the goal of using transformation strategies to engineer pathogen-resistant mosquitos will require the availability and thorough understanding of promoters that are induced at the right time and at the right place. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMPUTATIONAL IDENTIFICATION OF DENGUE VIRUS T-CELL EPITOPES Principal Investigator & Institution: Brusic, Vladimir; Computational Identification of Dengue v; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: The goal of this project is the application of computational solutions for systematic identification of promiscuous and allele-specific T-cell epitopes to the dengue virus genome for the development of an epitope-based genetic vaccine. Promiscuous Tcell epitopes are the best candidates for vaccine targets and vaccine formulations because they are potentially effective in the broad population. We will focus on systematic computational screening of the dengue virus genome and identification of the HLA-class II and class I "hot-spots" in the viral genome suitable for use in vaccine formulations. The hot-spots are regions of DNA that encode protein sequences with a high density of potential T-cell epitopes in the context of multiple HLA alleles, which are critical for the initiation and regulation of immune responses. Our published and new results show that computational methods can effectively be used for identification of class I (HLA-A2 and -A3 supertype) and class II (HLA-DR) promiscuous T-cell epitopes. These studies use peptide binding data, HLA sequence data, and computational methods of hidden Markov models and artificial neural networks. The preliminary models have been supported with experimental validation. This project will extend the computational screening approach to other major supertypes of class I (HLAA, HLA-B, and HLA-C) and class II (HLA-DQ) molecules. This project will be combined with projects 2 and 4 of this multi-project proposal, which will provide experimental validation of dengue virus hot-spots and enable the refinement of the computational selection of epitopes and the final selection of the peptide sequences to be encoded in a tetravalent dengue vaccine formulation designed to be effective in recipients covering a broad spectrum (>90%) of HLA alleles. Initially, this project will focus on identification of HLA class II T-cell epitopes from a single serotype, and later be extended to all four serotypes of dengue virus. The analysis will also be extended to HLA class I epitopes and analysis of their role in the severe manifestation of the infection, dengue hemorrhagic fever. Dengue virus has a small genome (10.7 kb RNA) and represents an ideal model for establishing protocols for systematic screening of complete genomes of pathogenic organisms. These results will provide the rationale for experiment planning and are expected to result in major savings in the cost and time required for vaccine

Studies

9

development. This multi-project program also provides a systematic analysis of the distribution of T-cell epitopes across complete genomes that can be applied in the future to other pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DENGUE EPITOPE. TETRAVALENT. MHC II TARGETED DNA VACCINE Principal Investigator & Institution: August, Joseph T.; Professor and Director; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: This goal of this project is to develop an epitope-based dengue virus DNA vaccine formulation, using a rational yet novel strategy that is based on advances in genomics, computational bioinformatics, and molecular and cell biology. These advances will be combined with access to disease-specific patient cohorts in an initial ex vivo clinical validation. The vaccine will be multivalent, encompassing neutralizing antibody epitopes of the four virus serotypes identified by analysis of overlapping peptides of the four serotype-specific envelope (Env) proteins. It will focus initially on sequences in residues 296 to 400 that form beta barrel-type structures known to participate in membrane fusion. Selection of the active peptides will be based on binding of human and mouse neutralizing antibodies and production of neutralizing antibodies by mice immunized with the peptides. Taking advantage of data obtained in Projects 1 and 2, the vaccine will also encode T-cell epitopes required for CD4* T-helper cell stimulation of both antibody and cellular immune responses: Candidate peptide sequences will be predicted by immuno-informatic analysis of the dengue gene sequences (Project 1) as clusters of promiscuous HLA-DR-binding motifs of about 50 amino acids. The candidate peptides will be tested (Project 2) for activation of human Tcells in an ex vivo assay using peripheral blood samples from individuals infected with dengue virus who have different HLA haplotypes. MHC I epitopes contained in the cluster hot-spot sequences will also be tested ex vivo for their possible anti-viral role or correlation with dengue hemorrhagic fever. The vaccine formulation will exclude unnecessary or deleterious dengue sequences, particularly those MHC I cytotoxic T-cell epitopes found to be associated with dengue hemorrhagic fever. In addition, epitopes included in the DNA vaccine constructs will be encoded as chimeras containing the celltargeting signals of the lysosome-associated membrane protein (LAMP), which provide the necessary trafficking of the vaccine antigens to the MHC II compartment for antigen processing and presentation. The final candidate human DNA vaccine formulation will contain the validated, tetravalent neutralizing antibody epitopes, promiscuous epitopes that bind to the diversity of HLA alleles in the human population, as well as LAMP targeting signals to direct the peptide epitopes to the MHC II compartment of antigenpresenting cells for enhanced antigen presentation to CD4+ T-helper cells. The formulated vaccine will also be validated by ex vivo assays of vaccine transfection of human peripheral blood dendritic cells and activation of B- and T cells of dengueinfected patients. This program is composed of platform technologies that, as developed in this dengue virus model system, can be applied to other hemorrhagic fever or other viruses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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•

Project Title: DENGUE TRANSMISSION

VIRUS

DETERMINANTS

OF

Principal Investigator & Institution: Rico-Hesse, Rebeca; Foundation for Biomedical Res San Antonio, Tx 782450549

VIRULENCE Scientist;

AND

Southwest

Timing: Fiscal Year 2001; Project Start 15-AUG-2001; Project End 31-MAY-2006 Summary: (provided by the applicant): The long-term goals of this project are to determine the structural (RNA and/or protein) and transmission (replication in Aedes aegypti) characteristics of those dengue type 2 virus variants that have produced dengue hemorrhagic fever (DHF) in humans throughout the world. We have determined the most probable viral structures involved in increased virulence and transmission by studying patient-derived virus variants. Currently we have modified an infectious clone of dengue type 2 virus to contain these structures and developed three assay systems in which to test virus phenotype. We will attempt to correlate dengue virus replication rates in vitro and in vivo with clinical and epidemiologic observations in different geographic areas (U.S. border, Mexico, Peru, Venezuela, Brazil). The identification of these determinants could provide critical information for the design of vaccines and/or anti-virals, which are currently unavailable for dengue. Specific aims: 1. To identify dengue virus factors responsible for increased replication in human and baboon target cells (monocytes and dendritic cells). Hypothesis: Specific viral structures are responsible for increased virus replication rates, which lead to severe disease (DHF) in certain individuals. 2. To identify dengue virus factors responsible for infection and dissemination in the natural mosquito vector from geographic regions with varying dengue epidemiology (presence or absence of DHF). Hypothesis: The mosquito vector promotes the transmission of those virus variants with increased replication rates (viremia) in the human host. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DNAVACCINE DENGUE/VACCINIA

DELIVERY

FOR

BIODEFENSE

WITH

Principal Investigator & Institution: King, Alan D.; Chief Scientific Officer; Cyto Pulse Sciences, Inc. 7513 Connelley Dr, Ste C Hanover, Md 21076 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-JAN-2004 Summary: (provided by applicant): The long-term project objective is the commercialization of a safe, effective, easy to use, and painless polynucleotide vaccine delivery system that can be used in polynucleotide vaccines for biodefense against NIAID Category A, B and C Pathogens. Polynucleotide vaccines are on the forefront of vaccine development. They are important because of the fast development times possible and because cell mediated immune responses can be induced. The delivery system proposed here will be effective for most polynucleotide vaccines. This delivery system specifically addresses the requirement as presented in the NIAID Strategic Plan for Biodefense Research, February 2002, page 8. In addition to Biodefense, this system will provide effective polynucleotide vaccine delivery for less lethal viruses, some cancers and some third world diseases. The defense and commercial applications are extensive. The polynucleotide vaccine delivery system described here uses a microneedle array with the polynucleotide coated right on the needle in the array. There are hundreds of needles each about 0.15 mm long. This array in inserted into the skin with the needle penetrating to about the basal lamina. After insertion the polynucleotide leaves the needle surface and an electric field is used to permeabilize dendritic and epithelial cell membranes to permit the polynucleotide to enter the cell. The system will

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be tested with the WRAIR/Cyto Pulse dengue DNA vaccine which will be used as a model for hemorrhagic fever viruses and the USAMRIID vaccinia DNA plasmid which is the primary vaccine for small pox. The specific aims of this project are to design and develop to FDA QSR Standards the vaccine delivery system prototype and to test the prototype in a human trial. This is a fast-track application. In Phase I, a system design will be completed including the hand-piece, microneedle array and miniature waveform generator. The coating chemistry and specific waveforms will be optimized in mice. In Phase II, a prototype of the final design will be completed. Safety and efficacy will be demonstrated in mice and safety will be demonstrated in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EVALUATION STUDIES OF A DENGUE-2 DNA VACCINE IN MONKEYS Principal Investigator & Institution: Martinez, Idali; Microbiology/Medical Zoology; University of Puerto Rico Med Sciences Medical Sciences Campus San Juan, Pr 00936 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Dengue fever and dengue hemorrhagic fever result from the infection with any of the four serotypes of dengue (DEN) viruses. These diseases have become a global public health problem, affecting 100 million people anually. Moreover, DEN viruses are potential bioterrorism agents since neither an effective treatment nor vaccine is available. Thus, research is needed to develop an effective and safe vaccine that will prevent infection and disease caused by any of these viruses. The objective of this study is to develop a DNA vaccine capable of inducing protective immune responses in rhesus macaques against DEN-2 virus infection. Our long-term objective is to develop a tetravalent DEN DNA vaccine. Our vaccine strategy is focused on the dengue envelope because this protein mediates the early binding and entry steps of infection. Neutralizing antibodies (Nab) against this protein were shown to be protective against pathogenic virus infection and disease. In this study we plan to evaluate immune responses generated in monkeys by our DNA vaccine candidate, VecD2 which encodes prM and env proteins of DEN-2, using four different vaccination regimens. Monkeys will be immunized with Vec-D2 either alone or absorbed onto polylactide-co-glycolide (PLG) microparticles, followed by the administration of an inactivated DEN-2 virus boost adjuvanted in MF59 or MF59 alone. Our hypothesis is that immune responses induced by Vec-D2 will be enhanced by coupling the plasmid DNA to PLG and that these responses could be further boosted by administration of inactivated virus in MF59. Immune responses will be monitored by ELISA, virus neutralization, CTL and proliferation assays. The level of protection induced by the different vaccine strategies against DEN-2 virus infection will be also ascertained: Complete protection will be determined by the absence of detectable viremia and of anamnestic immune responses. Results obtained from these studies will provide important information for the design and development of DNA vaccines expressing the envelope protein of DEN-l, DEN -3 and DEN-4. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FUNCTIONAL ANALYSIS OF DENGUE VIRUS ANTIGENS NS3 AND NS5 Principal Investigator & Institution: Padmanabhan, Radhakrishnan K.; Professor; Biochem and Molecular Biology; University of Kansas Medical Center Msn 1039 Kansas City, Ks 66160

12

Dengue Fever

Timing: Fiscal Year 2001; Project Start 01-JUL-1993; Project End 31-MAR-2002 Summary: Dengue viruses, members of Flaviviridae, are recognized as the causative agent of mosquito borne viral diseases affecting about 100 million people annually. Of these, more than 250,000 cases involve life threatening dengue hemorrhagic fever / dengue shock syndrome. The long term goal of this laboratory has been to dissect the biochemical mechanisms involved in dengue viral replication in the host. The specific objectives of this proposal are to define the specific molecular events during viral replication. An in vitro template dependent viral RNA replicase assay and the dengue infectious clone for in vitro analysis will be used to achieve these objectives, by fulfilling the following specific aims: 1. Conserved regions of the viral RNA required for both minus and plus strand RNA synthesis will be analyzed using the wild type and mutant subgenomic RNA templates in the viral replication assays. The subgenomic RNAs will be analyzed using RNA probing methods. The PI will analyze the effect of specific mutations on RNA synthesis using the viral replicase in vitro, and the growth phenotypes and replication efficiencies in vivo using the dengue infectious clone. 2. Viral replicase complexes will be isolated from recombinant vaccinia viruses expressing the wild type and mutant dengue viral protein precursor, which undergo processing and assembly in the infected cell in vivo. To study the mechanism of replication in the absence of virion assembly, a subgenomic dengue virus replicon expressing a readily quantifiable reporter gene product will be constructed. 3. Two hypotheses will be tested, using site directed mutants of NS3 in the in vitro viral replicase assay and the in vivo assay of mutant genomic RNAs trans-complemented by wild type NS3. First, the role of NS3, having NTPase and RNA helicase activities, is required for RNA synthesis at the 3' end in vitro. Second, a novel motif of NS3, Leu-Lys-Pro-Arg, is required for the 5'RNA triphosphatase activity of NS3. This enzyme activity is required in the first step for 5' capping of many viral RNAs. The PI propose that 5' capping is required for replication of RNA. 4. NS3/NS5 interaction is regulated by phosphorylation and subcellular location of NS5. The PI proposes to test the hypothesis that the nuclear NS5 regulates the expression of cellular gene(s) in response to viral infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETICS OF DENGUE VECTOR COMPETENCE IN AEDES AEGYPTI Principal Investigator & Institution: Black, William C.; Microbiology; Colorado State University Fort Collins, Co 80523

Associate

Professor;

Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (provided by applicant): Dengue fever is one of the most rapidly expanding diseases in the tropics with over 2 billion people at risk. Transmission of Dengue virus (DEN) involves a complex interaction between the genomes of the primary mosquito vector, Aedes aegypti, the virus, and its human host. The proposed research will focus on two of these components by examiningthe genetics of vector competence in Ae. aegypti and the degree to which vector competence is affected by genetic variance in the DEN virus. We have mapped Quantitative Trait Loci (QTL) affecting the ability of Ae. aegypri midgut to become infected with Dengue-2 virus (DEN2). These twomidgut infection barrier (MIB) QTL are called dmib2, dmib3 and were mapped to chromosomes II and III respectively. The primary goal of the proposed work is to use marker-assisted selection (MAS) to generate 4 strains of Ae. aegypri. These will be a strain homozygous susceptible at both loci (DS2), a strain homozygous refractory at both loci (DR2) and 2 strains homozygous susceptible at one locus and homozygous refractory at the other locus (DMIB2, DMIB3). These strains will provide an exceptional opportunity to

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elucidate the phenotypes associated with each genotype at the QTL underlying DEN transmission. DS2 will be used to isolate and map DEN barrier QTL from worldwide populations of Ae. aegypri to determine if additional QTL control DEN susceptibility and/or if alternate alleles exist at the currently identified QTL. DMIB2, DMIB3, and DR2 will be used to assess how alleles at both loci separately and together confer susceptibility in different DEN serotypes and genotypes in each of the 4 serotypes. DS2 and DR2 will be used in the construction of recombinant inbred lines for use in a subtractive hybridization approach to clone cDNAs putatively encoded bydmib3and to assist in a collaborative effort to positionally clone dmib3. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HERMES AND MARINER TRANSFORMATION OF AEDES AEGYPTI Principal Investigator & Institution: James, Anthony A.; Professor; Molecular Biology and Biochem; University of California Irvine Campus Dr Irvine, Ca 92697 Timing: Fiscal Year 2001; Project Start 01-DEC-1998; Project End 30-NOV-2003 Summary: Vector-borne diseases continue to cause significant mortality and morbidity in people throughout the world. While malaria and yellow fever are scourges of lesserdeveloped countries, the threat of Dengue fever is at the borders of the United States. Control of transmission of these diseases can be achieved by controlling their insect vectors. The development of mosquito transgenesis has made possible the producion of mosquitoes that have been altered by the stable insertion of exogenous genes. Our longterm goal is to produce transgenic mosquitoes that are resistant to infection by pathogens and use these as systems for studying pathogen-vector interactions as well as release organisms for programs seeking genetic control over the transmission of parasitic and viral diseases. Furthermoe, transormation makes it possible to study biochemical and molecular biological processes involved in basic aspects of mosuito physiology such as blood feeding and digestion, oogenesis and host seeking. Transposon-based genetic analysis of mosquitoes has the potential to identify many crucial genes whose expression is important for vector competence and vectorial capacity. Recently, we have shown that twso Class II transposable elements, Hermes and mariner, mediate the insertion of exogenous DNA into the chromosomes of the yellow fever mosquito. Aedes egypti (Jasinskiene et al., 1998; Coates et al., 1998). Further refinements of these transformation systems are reuqired to facilitate their use in producing pathogen- resistant mosquitoes and other strains for basic biological study.Towards these ends we propose the following specific aims: 1) develop methods for routine isolation of DNA fragments consisting of transposon-chromosome junctions from Hermes-transformed mosquito lines; 2) develop procedures and strains for remobilization of Hermes and Mariner chromosomal insertions; 3) produce transgenic strains of mosquitoes that exploit cre-loxp and FLP-FRT site-specific recombination for comparative promoter analysis. Successful accomplishment of these Specific Aim will result in robust and widely-applicable systems or mosquito transgenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HOST GENETICS AND SYMPTOMATIC DENGUE INFECTION Principal Investigator & Institution: Blanton, Ronald E.; Associate Professor; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Dengue continues to extend its range worldwide and has been a significant factor in peacekeeping efforts. Yet, its prevalence and

14

Dengue Fever

relationship to other important viral infections may make it a good model of flaviviral and hemorrhagic fever infection. A striking feature of infection with the dengue virus is that it is capable of producing a life-threatening illness or a mere laboratory finding associated with no symptoms at all. A potential source for these extremes in disease presentation following infection with dengue viruses is genetic differences in the human host. The 2'-5' oligoadenylate synthetase 1b (OAS 1b) gene of mice makes them resistant to all flaviviral infections. The human orthologs - the OAS 1, 2 & 3 genes - are very similar to the mouse genes. These genes are arranged in tandem, they may be coordinately regulated and probably arose by duplication. They are differentially induced by a variety of interferons and demonstrate many single nucleotide polymorphisms as well as several large variants. This proposal describes a limited casecontrol study of severe dengue cases from 2002 and 2003 in Salvador, Brazil for associations with these three OAS genes. There were between 40-60 confirmed cases of dengue hemorrhagic fever and thousands of cases of classic dengue in 2002 in this city. A survey of 20 SNP markers across the human OAS genes will be analyzed for allele and haplotype frequencies. The strength of association between alleles or haplotypes and clinical presentation will be assessed as relative risks and corrections will be made for population substructure and for multiple comparisons. In addition, demographic and familial data will be collected to assess the possibility for future familial linkage studies of severe or classic dengue in an R01. Besides excellent epidemiologic and laboratory investigators in Brazil, the project relies on a long history of collaboration between the groups, strong genetic epidemiology support from the Division of Genetic Epidemiology at Case Western Reserve University and serology laboratory support from co-investigators based at the Evandro Chagas Institute, Brazil and Fort Dettrick, MD. The results of this study may help predict populations at risk, may influence vaccine design or may aid in understanding and managing other viral hemorrhagic fevers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNOPATHOLOGICAL ANALYSIS HEMORRHAGIC FEVER/DENGUE SHOCK SYNDROMEN

OF

DENGUE

Principal Investigator & Institution: Ennis, Francis A.; Professor; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2001 Summary: Dengue virus infections are a serious cause of morbidity and mortality in many areas of the world. The pathogenesis of severe complications of dengue virus infection, dengue hemorrhagic fever (DHF) is important to elucidate for prevention and treatment of DHF. Epidemiological studies have shown that DHF is much more commonly observed during secondary infections with a different serotype of dengue virus from that which caused the primary infection, and it is assumed that DHF is caused by immunopathological mechanisms. We hypothesize that enhanced infection of monocytes by dengue virus-antibody complexes results in marked activation of dengue virus-specific CD4+ and CD8+ T cells and the production of high levels of cytokines which lead to DHF. The goal of this project is to define immunopathological mechanisms which induce DHF, using molecular immunological techniques. No animal models are available to study DHF; therefore, research using human subjects is required. We will elucidate immunopathological mechanisms by analyzing peripheral blood mononuclear cells (PBMC) and plasma of patients with DHF or with uncomplicated dengue fever (D) during the acute phase and after recovery. We will; 1) determine the levels of lymphokine mRNA in CD4+ and CD8+ T cells activated in vivo,

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15

2) determine whether dengue virus-specific CD4=T cells in patients with DHF are Th1 or Th2 by establishing CD4+T cell clones, 3) determine whether dengue virus-specific CD8=T cell clones also produce a characteristic set of lymphokines, and 4) analyze T cell receptor Valpha and Vbeta gene usage and determine whether T cell activation is oligoclonal in vivo. Monocytes are the most permissive human cells for dengue virus replication. We will determine the levels of cytokine mRNA in monocytes from patients with DHF or D. Furthermore, we will determine the levels of infectious dengue virusantibody complexes in the plasma of patients with DHF. The comparative ability of virus isolates from D and DHF patients to replicate in human monocytes will be tested in tested in this project. If significant differences in growth are detected, we will use this as a biologic marker for selecting typical strains for genome sequencing in project 3. We will define the immunological responses in vivo which result in DHF, based on these analyses of samples from patients with DHF or D. These analyses will provide basic immunological data concerning antibody and T cell responses to dengue virus that are needed for the development of safe and effective dengue vaccines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTERFERENCE MOSQUITOES

TO

DENGUE

VIRUS

REPLICATION

IN

Principal Investigator & Institution: Blair, Carol D.; Professor; Microbiology; Colorado State University Fort Collins, Co 80523 Timing: Fiscal Year 2002; Project Start 01-APR-1993; Project End 28-FEB-2007 Summary: (provided by the applicant): Dengue viruses, serotypes 1-4 are currently the most important mosquito-borne viruses affecting humans. It is estimated that 2.5 billion humans are at risk for infection. About 50-100 million cases of dengue fever (DF) and >100,000 cases of life-threatening dengue hemorrhagic fever (DHF) occur annually worldwide. A major factor contributing to the dramatic global emergence of DF and DIIF as public health concerns is the proliferation throughout the tropics of Aedes aegypti, the principal vector of DEN viruses. The long-term goal of this research is to define molecular strategies for reducing or eliminating the competence of Ae. aegypti to transmit DEN and other flaviviruses. Flavivirus replication in mosquito cells can be inhibited by intracellular expression of double-stranded RNA. Characteristics of RNAmediated interference in mosquito cells are very similar to those of evolutionarily conserved defense mechanisms in plants and other invertebrates such as Drosophila melanogaster. We hypothesize that RNA-mediated interference (RMI) in mosquitoes is a robust cellular process, homologous to those in other organisms, and that it can be manipulated to eliminate mosquito vector competence for flaviviruses. In this proposal, we plan studies to determine the detailed mechanism of RMI in mosquitoes. In addition to our mechanistic studies, we will examine the role of RMI in maintenance of flavivirus persistent infections in mosquitoes and in determining vector competence for flavivirus transmission. The specific aims of the proposal are as follows: 1.To define the mechanism for RNA-mediated interference (RMI)-to flaviviruses in mosquitoes. The molecular and biochemical characteristics of RMI in cultured mosquito cells and Ac. aegypti will be compared to those of posttranscriptional gene silencing (PTGS) in plants and RNA interference (RNAi) in Drosophila. 2:To determine the relationship between RNAi and persistent arbovirus infections in mosquitoes. The possibility that a counterdefensive dengue viral suppressor of RMI will be examined by use of a dengue virus infectious clone. 3. To determine the role of RNAi in refractoriness/susceptibility of mosquitoes to flaviviruses. Ac. aegypti genes associated with the RMI response will be characterized and mapped.

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Dengue Fever

Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MICROCHIP-BASED FIELD ASSAY TO DETECT DENGUE VIRUS Principal Investigator & Institution: Montagna, Richard A.; President\ceo; Innovative Biotechnologies International 335 Lang Blvd Grand Island, Ny 14072 Timing: Fiscal Year 2002; Project Start 01-JUN-2000; Project End 28-FEB-2004 Summary: (provided by applicant): Up to 100 million Dengue virus infections occur annually world wide. Associated pathologies (Dengue Hemorrhagic Fever, Dengue Shock Syndrome) result in >20,000 deaths annually, primarily in children. Dengue virus is endemic to tropical/subtropical regions, with high incidence rates in developing countries. Currently, no specific treatments or vaccines are available. Moreover, rapid, sensitive and specific diagnostics are lacking. Antibody ELISA tests lack specificity and require a host immune response; tissue culture assays require specialized laboratories and long incubation times. Phase I of this SBIR demonstrated the feasibility of linking a simple nucleic acid isolation technology to an isothermal method of nucleic acid amplification and a liposome-microchip biosensor detection technology for the clinical detection/subtyping of Dengue virus. This technology linkage permits specific and sensitive detection of Dengue infection in patients within 5 hours, has minimal equipment requirements, and can be provided at costs compatible with endemic area economies. Phase II proposes continued development/optimization of this assay system. Phase I design specifications will be used to produce and validate a prototype assay, produced in Jab batch quantities. Identified design and production modifications will be implemented to produce pilot batch lots of the assay that will be validated and clinically evaluated. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR ANALYSIS OF ALPHAVIRUS MEMBRANE FUSION PROTEIN Principal Investigator & Institution: Kielian, Margaret C.; Professor; Cell Biology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2001; Project Start 15-AUG-1995; Project End 31-JUL-2003 Summary: Alphaviruses and flaviviruses are the causative agents of severe human and animal illnesses such as encephalitis, polyarthritis, and dengue fever, with millions of cases in humans occurring per year. These enveloped viruses infect cells via a membrane fusion reaction that merges the virus and cell membranes and releases the viral genome into the cytoplasm. This fusion mechanism involves proteolytic cleavage of a companion subunit to activate the fusion protein, fusion protein trimerization via a non-coiled coil mechanism, and insertion of the internal fusion peptide into the target membrane. Fusion of this class of viruses thus is mechanistically quite different from the well characterize influenza virus fusion reaction, in which the fusion protein itself is cleaved and forms a trimeric coiled-coil structure. The goal of this proposal is to determine which the molecular mechanism of membrane fusion in the alphavirus Semliki Forest virus (SFV), a member of this class of viruses and a highly developed system to study membrane fusion. Three key features of the SFV fusion reaction will be addressed: 1. What are the functions of the E1 internal fusion peptide and transmembrane domain in fusion? Photolabeling will be use to define the region of E1 that inserts into the target membrane during fusion, and mutagenesis will test the role of specific residues in this region. The structure of virus containing a fusion-blocking mutation will be determine by cryo electron microscopy. The role of highly conserved

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glycine residues within the E1 transmembrane domain will be analyzed. 2. How does the E2 companion subunit interact with E1 and regulate its membrane fusion activity? Virus mutants with alterations in E1/E2 dimer stability will be selected and used to map the protein domains that are important in these subunit contacts. The effects of these mutations on fusion activity will be determined. 3. How does the E1 fusion protein oligomerize to form an E1 homotrimer, a critical step in fusion? This aim will characterize the minimal domain of E1 required to trimerization and the protein conformation changed involved in the E1 monomer to trimer transition. Molecular information on the fusion reaction of viruses in this class will make possible the design of specific inhibitors of key early steps in viral infection, and further our understanding of the ubiquitous membrane fusion reactions important to both viruses and cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALBOPICTUS

MOLECULAR

AND

QUANTITATIVE

VARIATION

IN

AE

Principal Investigator & Institution: Armbruster, Peter A.; Biology; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2001; Project Start 11-SEP-2001 Summary: The goals of this proposal are to evaluate the genetic consequences of a rapid range expansion and to assess micro- habitat specialization within a species of disease carrying mosquito. The Asian tiger mosquito, Aedes albopictus, is an important vector of dengue fever and is also able to transmit yellow fever and a variety of native North American arboviruses. Aedes albopictus was introduced into the United States in the vicinity of Houston, TX, in the mid- 1980's, and its distribution now extends from Florida to Illinois and Ohio. Comparing within- and between-population variability among ancestral (TX) and derived (FL, OH) populations will elucidate how genetic drift, migration, and selection at linked loci have distributed variability during the range expansion of this species in North America. In order to assess molecular variation, AFLP markers will be developed and used to characterize population structure throughout North America, and between tire breeding and tree-hole breeding populations. Genetic variation and differentiation of quantitative characters central to the rapid invasion and climatic adaptation of this species in North America will be examined, and used to investigate the extent to which variation and differentiation of AFLP markers accurately predicts variation and differentiation of quantitative characters. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POTENTIAL

MOLECULAR

DETERMINANTS

OF

DENGUE

EPIDEMIC

Principal Investigator & Institution: Beaty, Barry J.; Microbiology, Immunology & Pathology; Colorado State University Fort Collins, Co 80523 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: This project addresses emerging problems with Dengue (DEN) in Mexico. DEN and dengue hemorrhagic fever (DHF) have emerged as major public health problems. Indeed, more than 2 billion people are at risk for DEN infection, millions are infected annually with an estimated 100,000 cases of life threatening DHF, and the situation continues to deteriorate. Unfortunately, the epidemiologic circumstances that led to the emergence of DHF as a major public health problem in Southeast Asia in the 1960s and 1970s are now occuring in tropical America and Mexico. The vector mosquito, Aedes aegypti, is hyperendemic, and another major vector, Aedes albopictus, is

18

Dengue Fever

invading the country and may exacerbate the situation. Multiple serotypes and strains of DEN are now circulating simultaneously, and ominously, the incidence of DHF is increasing rapidly and DEN epidemics are occuring in cities in Northern Mexico. In this grant, we will, with colleagues from the Instituto Politecnica Nacional in Mexico City, from the Universidad Autonoma of Nuevo Leon in Monterrey, and the Universidad Autonoma of the Yucatan in Merida, investigate and elucidate the vector and viral genetic determinants of DEN transmission and virulence. This information will be used to develop and characterize biomarkers of vectors and viruses that pose substantial risk to human populations. Such information could be used to focus limited resources and and talents for control on situations with epidemic potential. Definition of vector and virus genotypes associated with DEN/DHF will permit eventual elucidation of mechanisms that determine virus transmission, disease, and epidemic potential and may lead to novel control and surveillance strategies for DEN in North America and elsewhere. These proposed studies will also provide invaluable information concerning the application of developed new technologies and approaches to other vector borne diseases of current and future public health importance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR EPIDEMIOLOGY OF DENGUE IN PEURTO RICO Principal Investigator & Institution: Mcmillan, W O.; University of Puerto Rico Rio Piedras Rio Piedras Sta San Juan, Pr 00931 Timing: Fiscal Year 2001 Summary: Description (Adapted from Application): In the last twenty years, dengue fever (DF) and its more severe manifestations, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), have emerged as a global health problem. Over this period, the incidence of the illness has increased 100-fold and hyperendemic transmission now characterizes most tropical countries, including Puerto Rico (PR). To understand the relationship between the rise of epidemic DF and DHIF/DSS and viral genotype diversity, genetic change will be examined in three dengue serotypes (DEN-1, DEN-2, and DEN-4) in Puerto Rico across an 18-year period. This time period traces the rise of DF and DHF/DSS on the island beginning with initial disease establishment and extending through repeated epidemic cycles. The investigators will sample serotype variation at two temporal scales--across multiple endemic and epidemic cycles, and at time points within single epidemic cycles. Nucleotide substitutions in the full complement of viral structural genes and two rapidly evolving non-structural genes will be used to construct a longitudinal series of phylogenetic trees for the DEN-1, DEN-2, and DEN-4 serotypes. These phylogenies will provide a temporal framework for tracing the history of the dengue epidemic in Puerto Rico. This framework will allow the investigators to: (1) document genotypic and evolutionary change over a period characterized by endemic and epidemic disease transmission; (2) correlate population genetic changes within and between dengue serotypes with cycles of endemic and epidemic transmission; (3) explore the nature of selection acting on different viral gene regions; (4) identify potentially significant amino acid positions and determine their association with disease severity and/or transmission potential; and (5) evaluate the importance of recombination in the evolution of the dengue virus in PR. This project is a synergistic collaboration linking molecular evolutionary biologists at the University of Puerto Rico with virologists at the Centers for Disease Control and Prevention (CDC). The study utilizes the CDC's rich viral sample bank and is the first systematic molecular epidemiological study of this emerging pandemic. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NOVEL ASSAYS FOR DENGUE DIFFERENTIAL DIAGNOSIS Principal Investigator & Institution: Heng-Phon, Too; Novel Assays for Degue Differential Diag; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: The goal of this project is the development and application of novel multiplex quantitative real time PCR (MqrtPCR) assays for differential diagnosis inpatients who may be multiply infected with dengue and other hemorrhagic fever pathogens. The rapid and accurate diagnosis of the several possible hemorrhagic viruses in patients suspected of dengue infection is critical for the identification of a large cohort of patients whose peripheral blood sample will be examined in this program to assess the epitopebased dengue vaccine that is the primary goal of this multi-project program. These assays will also be beneficial in furthering the epidemiological surveillance of dengue infections in Brazil. A principal and unique feature of the proposed assay is its multiplex quantitative real-time PCR technology and its capacity for genotype-specific differential diagnosis of infectious agents currently endemic in Brazil: dengue viruses, West Nile virus, yellow fever virus, hantavirus and leptospira species. A multiplex assay that will simultaneously detect conserved sequences of these infectious agents, all of which may have similar clinical symptoms, will allow the rapid diagnoses of patients at an early phase of infection, an important aspect in differential diagnosis. This assay technology will also be used in multiplex format to distinguish any combination of the four dengue serotype viruses in a single operation. This assay technology has already been developed for the quantitative real time PCR assay of replicating dengue serotype 2. The optimal conditions and parameters of these assays, with respect to their sensitivity and specificity for multiplex differential diagnosis of other viruses and the four dengue serotypes will be determined in laboratory control studies. The validated protocols and reagents will then be made available to workers in Brazil for application to the field studies with patient cohorts. Accurate diagnoses of these patients are crucial if the blood samples are to be used for the ex vivo biological validation of the predicted peptide epitopes and response to the vaccine formulation described in Projects 1, 2 and 4. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NOVEL GENETIC MARKERS FOR THE YELLOW FEVER MOSQUITO Principal Investigator & Institution: Tu, Zhijian; Assistant Professor; Biochemistry; Virginia Polytechnic Inst and St Univ 460 Turner Street, Suite 306 Blacksburg, Va 24060 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 14-SEP-2004 Summary: (provided by the applicant): The yellow fever mosquito, Aedes aegypti, is the main vector of the most important arthropod-borne viral diseases affecting humans, namely yellow fever and dengue fever. Efficient vector control programs and informative epidemiological studies, which are essential for the control of these diseases, requires a better understanding of the genetic variations within and between Ae. aegypti vector populations. The objective of this proposed research is to develop a novel approach to analyze the genetic variations in Ae. aegypti populations, which offers several significant advantages and complements existing methods. Our approach is based on recently demonstrated insertion polymorphism of a family of highly reiterated short interspersed repetitive elements (SINEs) named Feilai in Ae. aegypti (Tu, 1999, Mol. Biol. Evol. 16:760-772). Here we propose to develop a systematic approach to isolate these polymorphic Feilai insertion markers. Like the Alu insertion markers in humans (e.g., de Pancorbo et al., 2001, Hum. Genet. 109:224-233; Roy-Engel et al., 2001, Genetics 159:279-290). Feilai markers can offer several major advantages including the

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ability to distinguish between ancestral and derived states of the two alleles, the extreme ease of use, and the potential for high-throughput assays. During this R03 pilot project, we will pursue the following Specific Aims: 1) Develop a high-throughput assay for the co-dominant FIP markers; 2) Construct a more detailed phylogenetic framework, to classify Ae. aegypti Feilai subfamilies; 3) Develop different approaches to systematically isolate co-dominant FIP markers, with the focus on representative sampling and direct testing of different Feilai subfamilies and/or groups. The future goals extending beyond this proposed R03 pilot project are to isolate a large number of high-throughput Feilai insertion polymorphism markers, and to use these powerful markers to study the genetic variability and the genetic basis of vectorial competence of Ae. aegypti in natural populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PACIFIC CENTER FOR EMERGING INFECTIOUS DISEASES RESEARCH Principal Investigator & Institution: Yanagihara, Richard T.; Pediatrics; University of Hawaii at Manoa 2500 Campus Rd Honolulu, Hi 96822 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): In response to a regional resurgence of infectious diseases and consistent with a high-priority institutional initiative to establish the AsiaPacific Institute for Tropical Medicine and Infectious Diseases, this application proposes to develop the Pacific Center for Emerging Infectious Diseases Research at the University of Hawai'i at Manoa. By drawing on the complementary strengths and expertise within the John A. Burns School of Medicine, the Pacific Biomedical Research Center, and the Cancer Research Center of Hawai'i, as well as the State of Hawai'i Department of Health, the new Center will be anchored by the tenets of transdisciplinary research. Projects will be linked by a unifying research focus on the molecular epidemiology and pathogenesis of infectious diseases, which are of local and regional relevance and which disproportionately affect under-served ethnic minority communities in Hawai'i and the Asia-Pacific region. Specifically, studies will be conducted on the natural history of human papillomavirus infection in heterosexual men, the immunopathogenesis of dengue fever, and the molecular epidemiology and adhesion properties on group A streptococci in relation to high-incidence acute rheumatic fever in Hawai'i. Newfound knowledge from these research projects will provide improved strategies for prevention and control of these regionally important infectious diseases. The overall objectives of the proposed Center will be achieved by the following specific aims: 1. Build institutional capacity by mentoring a cadre of promising young faculty to conduct research on infectious diseases of medical importance to the Asia-Pacific region. 2. Improve research competitiveness by enhancing the capacity for mentoring and expanding the capability of the technical support infrastructure. 3. Diversify the research breadth and trans-disciplinary scope of the Center through targeted recruitment and retention of funded faculty with complementary expertise and through centralization of laboratory space and researchsupport operations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PRECLINICAL DEVELOPMENT OF A RECOMBINANT DENGUE VACCINE Principal Investigator & Institution: Weeks-Levy, Carolyn L.; Hawaii Biotech, Inc. Aiea, Hi 967013900

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Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 28-FEB-2006 Summary: (provided by applicant): Dengue viruses (category A pathogen) are estimated to infect 100 million people annually and are considered to cause one of the most important arthropod-borne viral diseases in terms of human morbidity and mortality. Although 40% of the world's population can benefit from a dengue vaccine, there is no clear pathway to commercialization of such a vaccine. Barriers to commitment of the necessary funds to drive commercialization derive from scientific, market, medical and investment-funding uncertainties that, added together, create unacceptable risk for today's companies. Dengue and dengue hemorrhagic fever are caused by one of four closely related virus serotypes. Infection with one of the serotypes does not provide cross-protective immunity from the other serotypes and is believed to exacerbate the disease upon infection with a second serotype. To date, no dengue vaccine has been licensed and human clinical trials of several dengue vaccine candidates have not demonstrated durable immunity against all four dengue serotypes. Hawaii Biotech, Inc. has developed a multicomponent, recombinant subunit dengue vaccine that has the potential to elicit long-lasting immunity to all four dengue serotypes. The vaccine will be developed for phase I clinical trials to be performed in collaboration with The Walter Reed Army Institute of Research. The vast majority of the preclinical development work outlined in this proposal will be performed under Good Manufacturing Practice (cGMP) and Good Laboratory Practice (GLP). The preclinical development work encompasses scale-up and cGMP manufacture of recombinant dengue antigens covering the four dengue serotypes, purification of the antigens, testing and release of the vaccine prior to use in humans, toxicology testing of the vaccine in animal models, fill/finish of the vaccine active pharmaceutical ingredient (API) and adjuvant API and preparation of an Investigational New Drug Application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF ENERGY METABOLISM IN MOSQUITOES Principal Investigator & Institution: Wells, Michael A.; Associate Biochemistry; University of Arizona P O Box 3308 Tucson, Az 857223308

Professor;

Timing: Fiscal Year 2001; Project Start 15-FEB-2001; Project End 31-JAN-2006 Summary: Female mosquitoes require a blood meal from a vertebrate host to produce eggs. The public health importance of mosquitoes derives from the fact that while obtaining such a blood meal from a human host the mosquito is able to transmit diseases, such as malaria and dengue, which world-wide are responsible for millions of deaths per year. We need to significantly increase our understanding of the biology of mosquitoes. One area that has been neglected, so far, is fundamental metabolic studies directed towards understanding how the female mosquito utilizes the components of the blood meal. At most 20 percent of the blood meal amino acids are used for egg production and the purpose of this proposal is determine the fate of the other 80 percent. Thus, this proposal is concerned with following the fate amino acids derived from blood meal proteins under a variety of nutritional states. In addition, we propose to assess the role of preexisting energy reserves in the female mosquito during blood meal utilization. Once the relevant pathways have been defined, future studies will be concerned with mechanisms that regulate the pathways under different nutritional, behavioral and environmental conditions. In this proposal we plan to quantitatively examine the fate of amino acids derived from blood meal proteins in Aedes aegypti, the vector of dengue fever and Anopheles albimanus, a vector of malaria in Central and South America. The following specific aims are proposed: 1. Determine the metabolic fate of 14C-labeled blood meal protein amino acids. 2. Determine the metabolic fate of

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preexisting energy stores, specifically glycogen and lipid, following a blood meal. 3. Characterize the metabolism of blood meal protein amino acids. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RNA-PROTEIN INTERACTIONS IN THE FLAVIVIRIDAE VIRUSES. Principal Investigator & Institution: Gomila, Raul C.; Microbiol & Molecular Genetics; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 06-SEP-2001; Project End 14-SEP-2004 Summary: (provided by applicant): RNA viruses depend on the interaction of their genomes with viral and cellular proteins to carry out many of the steps in their life cycle. The long-term objective of this proposal is to understand molecular mechanisms of interaction between viral RNAs and viral and cellular proteins. The specific aims of the proposal are designed to characterize the interactions of West Nile and Dengue virus RNAs with eEF-1A, and of hepatitis C virus (HCV) RNA with the HCV core protein. Cellular proteins have been reported to be present in the replication complexes of many viruses. However, for most of these proteins, the role they play in viral replication remains unknown. The studies presented here to characterize the interaction between eEF-1A and two important flaviviruses represent the initial steps in the elucidation of the role of eEF-1A in the life cycle of these viruses. The interaction between the HCV core protein and the RNA genome could be important for viral encapsidation. In addition, it could also be involved in other processes such as genome replication and translation of the viral mRNA. Identifying the specific domains and sequences that are involved in this interaction is an important step in order to better understand the virus life cycle. Gel shift assays, as well as footprinting experiments will be done in order to characterize the RNA-protein interactions. HCV infection is widely spread across the world, as it is estimated that approximately 3% of the world population is infected. Dengue virus infects more than 100 million cases of Dengue fever annually, and West Nile virus recently emerged in North America for the first time. Therefore, the elucidation of the molecular mechanism of interaction between the RNA and proteins of these viruses could be important in order to design effective antiviral therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURE BASED ANALYSIS OF DENGUE VIRUS SERINE PROTEASE Principal Investigator & Institution: Murthy, Krishna H.; Center/Macromolecualr Crystall; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 31-MAY-2005 Summary: (adapted from the applicant's abstract): Dengue viruses, members of the Flaviviridae are recognized as the causative agent or one of the most important mosquito-borne viral diseases of humans affecting 100 million people annually. Of these, more than 250,000 cases involve life-threatening dengue hemorrhagic fever/dengue shock syndrome with no effective chemotherapy or vaccine currently available. One of the long term goals of this study is to dissect the biochemical mechanism(s) by which dengue virus replicates in the permissive host cells. Processing of the viral polyprotein precursor in host cells is carried out by the two-component viral protease, NS2B/NS3, which plays a pivotal role in the virus life cycle. A hydrophilic region of 40 amino acids of NS2B, SN2B(H), serves as an activator of the catalytic subunit of the NS3 serine protease domain (NS3-pro). In addition to the protease activity, NS3 has RNA-stimulated NTPase, RNA helicase, and 5' RNA triphosphatase

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activities. The structures of NS3-pro and the NS3-pro/mung bean inhibitor (MbBBI) complex have been determined. Kinetic characterization of NS3-pro and NS2B(H)/NS3pro have also been carried out. The objectiveof the research proposed in this application is to dissect the molecular mechanism of activation of dengue virus serine protease using structural and biochemical approaches. This research objective will be accomplished by the completion of the following Specific Aims: (1)To understand the biochemical mechanism of the viral protease, kinetic parameters of both NS3-pro and NS2B(H)/NS3-pro will be determined using fluorogenic peptide substrates and protease inhibitors. (2) To elucidate the mechanism of activation of NS3-pro by NS2B(H), structures of ternary complexes of NS2B(H)/NS3-pro and a suitable serine protease inhibitors will be determined. (3) Site specific mutations suggested by the structure of NS3-pro/MbBBI will be made and characterized functionally and structurally. The work to be carried out will result in laying the necessary structural foundation for structure- assisted design of specific inhibitors of the dengue virus protease. It will also permit a structural definition of alternate targets for inhibition of the protease and their detailed evaluation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE AEDES AEGYPTI GENOME PROJECT Principal Investigator & Institution: Severson, David W.; Associate Professor; Biological Sciences; University of Notre Dame 511 Main Bldg Notre Dame, in 46556 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 30-JUN-2004 Summary: (provided by applicant): Arthropod-borne viral diseases have re-emerged as major health problems in most tropical countries. For example, the incidence of dengue fever has increased greatly over the past 20 years, recently including its hemorrhagic form with associated human fatalities. The mosquito Aedes aegypti is the primary vector. In addition, A. aegypti is an excellent laboratory model for examining vector interaction with a malaria parasite (Plasmodium gallinaceum) and a lymphatic filarioid nematode (Brugia malayi). Whole genome sequence data is available for humans, Drosophila melanogaster, the malaria parasite vector Anopheles gambiae, the malaria parasite Plasmodium falciparum, and several other parasite genome projects are underway. This proposal seeks to initiate an A. aegypti genome project, with an expectation that complete knowledge of the mosquito vector, parasite and human genomes will promote and foster new disease control strategies. The immediate objectives of this project are to: (1) sequence both ends of 40,000 cDNAs derived from normalized libraries produced from 4 specific mRNA sources (from pooled mRNAs isolated from various developmental stages and adult tissues and from females exposed to infected blood meals containing dengue virus, a malaria parasite, and a filarial worm parasite), (2) to sequence both ends of 50,000 genomic DNA Bacterial Artificial Chromosome (BAC) clones, and (3) to use fluorescent in situ hybridization (FISH) technology to physically map 1000 A. aegypti BAC clones to metaphase chromosomes. These aims will develop a body of genome information including EST sequences, genomic sequences, and the physical map positions of large genomic clones that will enhance gene discovery, and also provide critical tools for an eventual complete genome sequencing project. The proposal complements a nearly completed genome project to examine the primary malaria vector, Anopheles gambiae, as the 2 species reflect the range of genome size and organization among mosquito species. The long range goal is to promote and foster collaboration between funding agencies to support an effort to sequence the entire A. aegypti genome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRYPTOPHAN METABOLISM IN MOSQUITOES Principal Investigator & Institution: Li, Jianyong; Animal Sciences; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAR-2003 Summary: Mosquitoes are important disease vectors, responsible for transmission of numerous viral, bacterial and parasitic diseases, such as malaria, dengue fever, yellow fever, and filariasis. Malaria, caused by infection with species of Plasmodium, is a devastating, disease which affects up to 500 million people world-wide, killing as many as 2 million a year. The development of drug resistant parasites, and insecticide resistant mosquito vectors urgently demands that new and innovative mosquito or parasite control strategies be developed. Disruption of the required physio-biochemical processes that are necessary for the normal development of either mosquitoes or malaria parasites is one approach for malaria control. A novel transaminase that is specific for the transamination of a chemically reactive and potentially toxic 3-hydroxykynurenine, formed during tryptophan oxidation, to stable xanthurenic acid is identified in Aedes aegypti mosquitoes, and this enzyme is tightly regulated with high activity in larvae and adult females after a bloodmeal. Our recent data show that xanthurenic acid also stimulates gametogenesis of Plasmodium parasites, suggesting this pathway may play critical role in initiating Plasmodium development in mosquito vectors. The long term goal of this research is to achieve a full understanding of the pathways and mechanisms governing the regulation of this enzyme in mosquito vectors. The specific aims of the proposed research are (I) to purify and characterize the 3-hydroxykynurenine transaminase from mosquitoes by various biochemical techniques, (II) to initiate studies concerning the genetic regulation of this transaminase in mosquitoes during development with various molecular techniques, which includes preparation of a cDNA library from mosquito larvae, isolation of 3-hydroxykynurenine transaminase cDNA from the library, and study of gene expression of the 3-hydroxykynurenine transaminase in mosquitoes during development, and (III) to study the transamination pathway of 3-hydroxykynurenine to xanthurenic acid in Anopheles mosquitoes. Our hypotheses are that this transamination pathway is critical for the normal development of mosquitoes and also may play a critical role in stimulating Plasmodium development; consequently, understanding the mechanism controlling its regulation could have a significant impact on future efforts to negatively interfere with vector development through innovative mosquito control strategies and also may provide insight into developing novel tools for the control of malaria parasites by interrupting gametogenesis of Plasmodium in mosquito vectors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VIRUS-HOST INTERACTIONS IN EUKARYOTIC CELLS Principal Investigator & Institution: Pestka, Sidney; Adjunct Professor; Molecular Genetics, Microbiology and Immunology; Univ of Med/Dent Nj-R W Johnson Med Sch Robert Wood Johnson Medical Sch Piscataway, Nj 08854 Timing: Fiscal Year 2003; Project Start 30-SEP-1991; Project End 31-AUG-2008 Summary: (provided by applicant): This proposal is for continued support of a new training program in virology, with a major focus on virus-host interactions in eukaryotic ceils. Twenty two faculty members will participate, all of whom are members of at least one graduate program composed of faculty at both Rutgers University (RU) and UMDNJ-Robert Wood Johnson (RWJ) Medical School: the Coordinated Graduate Program in Microbiology and Molecular Genetics of RU and UMDNJ and the Graduate

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Program in Molecular Genetics, Microbiology and Immunology of UMDNJ-the Graduate School of Biomedical Sciences. These two programs share recruitment, admissions curricula, and other training activities. This training program provides education in physical techniques, recombinant DNA, immunology, host and tissue trophic mechanisms, and host defense mechanisms as applied to the problem of viral infection of eukaryotic hosts. These trainees represent a group of highly trained professionals who will apply their skills to the viral infectious disease problems now confronting the United States: the AIDS epidemic, the entry of dengue fever into this country, and frequent influenza outbreaks and less frequent pandemics. The agents responsible for these problems (and a variety of others) are being intensively studied here, as are research techniques applicable to many other health-related areas. In addition to the techniques of modern biotechnology, trainees become familiar with molecular approaches to vaccine development, approaches to molecular intervention in viral life cycles, and the molecular biology of the interferons and their receptors and signal transduction mechanisms. This program recruits trainees from a large pool of outstanding applicants, including those in an ongoing undergraduate minority biomedical careers program at UMDNJ-RWJ Medical School. The training faculty currently supervise minority and handicapped trainees. The current application emphasizes that the twenty-two laboratories comprising the training grant provide a cohesive group whose members interact well and extensively together in providing training in virology and virus-host interactions. Furthermore, the wide breadth of the investigators in this program provides its unique strength in developing genuinely novel and unanticipated advances in this area. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “dengue fever” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for dengue fever in the PubMed Central database: •

[alpha]-Glucosidase Inhibitors Reduce Dengue Virus Production by Affecting the Initial Steps of Virion Morphogenesis in the Endoplasmic Reticulum. by Courageot MP, Frenkiel MP, Duarte Dos Santos C, Deubel V, Despres P.; 2000 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111573

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A model of dengue fever. by Derouich M, Boutayeb A, Twizell EH.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153427

3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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Activation of endothelial cells via antibody-enhanced dengue virus infection of peripheral blood monocytes. by Anderson R, Wang S, Osiowy C, Issekutz AC.; 1997 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191637

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Activation of Terminally Differentiated Human Monocytes/Macrophages by Dengue Virus: Productive Infection, Hierarchical Production of Innate Cytokines and Chemokines, and the Synergistic Effect of Lipopolysaccharide. by Chen YC, Wang SY.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136495

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Advances in dengue diagnosis. by Guzman MG, Kouri G.; 1996 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=170421

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An Antigen Capture Enzyme-Linked Immunosorbent Assay Reveals High Levels of the Dengue Virus Protein NS1 in the Sera of Infected Patients. by Young PR, Hilditch PA, Bletchly C, Halloran W.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86336

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Antibodies against prM protein distinguish between previous infection with dengue and Japanese encephalitis viruses. by Cardosa MJ, Wang SM, Sum MS, Tio PH.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113253

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Apoptosis in the Mouse Central Nervous System in Response to Infection with Mouse-Neurovirulent Dengue Viruses. by Despres P, Frenkiel MP, Ceccaldi PE, Duarte Dos Santos C, Deubel V.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109443

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Bacterial Lipopolysaccharide Inhibits Dengue Virus Infection of Primary Human Monocytes/Macrophages by Blockade of Virus Entry via a CD14-Dependent Mechanism. by Chen YC, Wang SY, King CC.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104020

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Bystander Target Cell Lysis and Cytokine Production by Dengue Virus-Specific Human CD4 + Cytotoxic T-Lymphocyte Clones. by Gagnon SJ, Ennis FA, Rothman AL.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104137

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Chemical Mutagenesis of Dengue Virus Type 4 Yields Mutant Viruses Which Are Temperature Sensitive in Vero Cells or Human Liver Cells and Attenuated in Mice. by Blaney JE Jr, Johnson DH, Firestone CY, Hanson CT, Murphy BR, Whitehead SS.; 2001 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114545

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Chimeric Yellow Fever/Dengue Virus as a Candidate Dengue Vaccine: Quantitation of the Dengue Virus-Specific CD8 T-Cell Response. by van der Most RG, MuraliKrishna K, Ahmed R, Strauss JH.; 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112342

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Clinical Evaluation of a Rapid Immunochromatographic Test for the Diagnosis of Dengue Virus Infection. by Sang CT, Hoon LS, Cuzzubbo A, Devine P.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104533

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Comparison of PanBio Dengue Duo Enzyme-Linked Immunosorbent Assay (ELISA) and MRL Dengue Fever Virus Immunoglobulin M Capture ELISA for Diagnosis of

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Dengue Virus Infections in Southeast Asia. by Cuzzubbo AJ, Vaughn DW, Nisalak A, Solomon T, Kalayanarooj S, Aaskov J, Dung NM, Devine PL.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95759 •

Comparison of Rapid Centrifugation Assay with Conventional Tissue Culture Method for Isolation of Dengue 2 Virus in C6/36-HT Cells. by Roche RR, Alvarez M, Guzman MG, Morier L, Kouri G.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87421

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Comparison of Two Rapid Diagnostic Assays for Detection of Immunoglobulin M Antibodies to Dengue Virus. by Wu SJ, Paxton H, Hanson B, Kung CG, Chen TB, Rossi C, Vaughn DW, Murphy GS, Hayes CG.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95832

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Construction, Safety, and Immunogenicity in Nonhuman Primates of a Chimeric Yellow Fever-Dengue Virus Tetravalent Vaccine. by Guirakhoo F, Arroyo J, Pugachev KV, Miller C, Zhang ZX, Weltzin R, Georgakopoulos K, Catalan J, Ocran S, Soike K, Ratterree M, Monath TP.; 2001 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114964

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Dengue and Dengue Hemorrhagic Fever. by Gubler DJ.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88892

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Dengue fever in pregnancy: a case report. by Phupong V.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=61035

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Dengue Type 3 Virus in Plasma Is a Population of Closely Related Genomes: Quasispecies. by Wang WK, Lin SR, Lee CM, King CC, Chang SC.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=155095

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Dengue type 4 virus mutants containing deletions in the 3' noncoding region of the RNA genome: analysis of growth restriction in cell culture and altered viremia pattern and immunogenicity in rhesus monkeys. by Men R, Bray M, Clark D, Chanock RM, Lai CJ.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190271

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Dengue Virus Selectively Induces Human Mast Cell Chemokine Production. by King CA, Anderson R, Marshall JS.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155122

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Dengue Virus Structural Differences That Correlate with Pathogenesis. by Leitmeyer KC, Vaughn DW, Watts DM, Salas R, Villalobos I, de Chacon, Ramos C, Rico-Hesse R.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112516

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Dengue: The Risk to Developed and Developing Countries. by Monath TP.; 1994 Mar 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43378

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Derivation and Characterization of a Dengue Type 1 Host Range-Restricted Mutant Virus That Is Attenuated and Highly Immunogenic in Monkeys. by Markoff L, Pang X, Houng HS, Falgout B, Olsen R, Jones E, Polo S.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136019

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Detection of Dengue Viral RNA Using a Nucleic Acid Sequence-Based Amplification Assay. by Wu SJ, Lee EM, Putvatana R, Shurtliff RN, Porter KR, Suharyono W, Watts DM, King CC, Murphy GS, Hayes CG, Romano JW.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88241

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Detection of Dengue Virus Replication in Peripheral Blood Mononuclear Cells from Dengue Virus Type 2-Infected Patients by a Reverse Transcription-Real-Time PCR Assay. by Wang WK, Sung TL, Tsai YC, Kao CL, Chang SM, King CC.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154639

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Detection of Dengue Virus RNA in Patients after Primary or Secondary Dengue Infection by Using the TaqMan Automated Amplification System. by Laue T, Emmerich P, Schmitz H.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85278

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Detection of Specific Antibodies in Saliva during Dengue Infection. by Cuzzubbo AJ, Vaughn DW, Nisalak A, Suntayakorn S, Aaskov J, Devine PL.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105280

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Development and Evaluation of Serotype- and Group-Specific Fluorogenic Reverse Transcriptase PCR (TaqMan) Assays for Dengue Virus. by Callahan JD, Wu SJ, DionSchultz A, Mangold BE, Peruski LF, Watts DM, Porter KR, Murphy GR, Suharyono W, King CC, Hayes CG, Temenak JJ.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88496

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Development of dengue virus replicons expressing HIV-1 gp120 and other heterologous genes: a potential future tool for dual vaccination against dengue virus and HIV. by Pang X, Zhang M, Dayton AI.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=61042

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Diagnosis of Dengue Virus Infection by Detection of Specific Immunoglobulin M (IgM) and IgA Antibodies in Serum and Saliva. by Balmaseda A, Guzman MG, Hammond S, Robleto G, Flores C, Tellez Y, Videa E, Saborio S, Perez L, Sandoval E, Rodriguez Y, Harris E.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150529

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Diverse Dengue Type 2 Virus Populations Contain Recombinant and Both Parental Viruses in a Single Mosquito Host. by Craig S, Thu HM, Lowry K, Wang XF, Holmes EC, Aaskov J.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150639

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Enzyme-Linked Immunosorbent Assay Specific to Dengue Virus Type 1 Nonstructural Protein NS1 Reveals Circulation of the Antigen in the Blood during the Acute Phase of Disease in Patients Experiencing Primary or Secondary Infections. by Alcon S, Talarmin A, Debruyne M, Falconar A, Deubel V, Flamand M.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153354

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Evaluation of a Capture Screening Enzyme-Linked Immunosorbent Assay for Combined Determination of Immunoglobulin M and G Antibodies Produced during Dengue Infection. by Kit Lam S, Lan Ew C, Mitchell JL, Cuzzubbo AJ, Devine PL.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95970

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Evaluation of a Commercial Capture Enzyme-Linked Immunosorbent Assay for Detection of Immunoglobulin M and G Antibodies Produced during Dengue Infection. by Sang CT, Cuzzubbo AJ, Devine PL.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=121382

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Evaluation of a Commercially Available Immunoglobulin M Capture Enzyme-Linked Immunosorbent Assay Kit for Diagnosing Acute Dengue Infections. by Porter KR, Widjaja S, Darmawan H, Lohita, Hadiwijaya SH, Maroef CN, Suharyono W, Tan R.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95765

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Evaluation of a dipstick enzyme-linked immunosorbent assay for detection of antibodies to dengue virus. by Wu SJ, Hanson B, Paxton H, Nisalak A, Vaughn DW, Rossi C, Henchal EA, Porter KR, Watts DM, Hayes CG.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170549

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Evaluation of a Rapid Immunochromatographic Test for Diagnosis of Dengue Virus Infection. by Vaughn DW, Nisalak A, Kalayanarooj S, Solomon T, Dung NM, Cuzzubbo A, Devine PL.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124841

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Evaluation of Four Methods for Detection of Immunoglobulin M Antibodies to Dengue Virus. by Branch SL, Levett PN.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95727

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Evaluation of Six Immunoassays for Detection of Dengue Virus-Specific Immunoglobulin M and G Antibodies. by Groen J, Koraka P, Velzing J, Copra C, Osterhaus AD.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95976

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Evaluation of the MRL Diagnostics Dengue Fever Virus IgM Capture ELISA and the PanBio Rapid Immunochromatographic Test for Diagnosis of Dengue Fever in Jamaica. by Palmer CJ, King SD, Cuadrado RR, Perez E, Baum M, Ager AL.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84845

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Evolutionary Relationships of Endemic/Epidemic and Sylvatic Dengue Viruses. by Wang E, Ni H, Xu R, Barrett AD, Watowich SJ, Gubler DJ, Weaver SC.; 2000 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111823

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Flow Cytometry Compared with Indirect Immunofluorescence for Rapid Detection of Dengue Virus Type 1 after Amplification in Tissue Culture. by Kao CL, Wu MC, Chiu YH, Lin JL, Wu YC, Yueh YY, Chen LK, Shaio MF, King CC.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88405

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Human Dendritic Cells Are Activated by Dengue Virus Infection: Enhancement by Gamma Interferon and Implications for Disease Pathogenesis. by Libraty DH, Pichyangkul S, Ajariyakhajorn C, Endy TP, Ennis FA.; 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114841

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Human Dengue Antibodies against Structural and Nonstructural Proteins. by Valdes K, Alvarez M, Pupo M, Vazquez S, Rodriguez R, Guzman MG.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95972

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Identification of a Putative Coreceptor on Vero Cells That Participates in Dengue 4 Virus Infection. by Martinez-Barragan JD, del Angel RM.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115024

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Identification of amino acids involved in recognition by dengue virus NS3-specific, HLA-DR15-restricted cytotoxic CD4+ T-cell clones. by Zeng L, Kurane I, Okamoto Y, Ennis FA, Brinton MA.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190173

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Identification of B-Cell Epitope of Dengue Virus Type 1 and Its Application in Diagnosis of Patients. by Wu HC, Huang YL, Chao TT, Jan JT, Huang JL, Chiang HY, King CC, Shaio MF.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87860

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Immunoglobulin A-Specific Capture Enzyme-Linked Immunosorbent Assay for Diagnosis of Dengue Fever. by Talarmin A, Labeau B, Lelarge J, Sarthou JL.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104797

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Inflammatory Mediators in Dengue Virus Infection in Children: Interleukin-8 and Its Relationship to Neutrophil Degranulation. by Juffrie M, van der Meer GM, Hack CE, Haasnoot K, Sutaryo, Veerman AJ, Thijs LG.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97195

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Kinetics of Dengue Virus-Specific Serum Immunoglobulin Classes and Subclasses Correlate with Clinical Outcome of Infection. by Koraka P, Suharti C, Setiati TE, Mairuhu AT, Van Gorp E, Hack CE, Juffrie M, Sutaryo J, Van Der Meer GM, Groen J, Osterhaus AD.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88545

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Low Specificity of an Immunochromatographic Serological Assay for Diagnosis of Dengue Fever in Travelers Returning with Malaria. by Charrel RN, de Lamballerie X.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130116

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Monkeys immunized with intertypic chimeric dengue viruses are protected against wild-type virus challenge. by Bray M, Men R, Lai CJ.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190310

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Potential Application of Nonstructural Protein NS1 Serotype-Specific Immunoglobulin G Enzyme-Linked Immunosorbent Assay in the Seroepidemiologic Study of Dengue Virus Infection: Correlation of Results with Those of the Plaque Reduction Neutralization Test. by Shu PY, Chen LK, Chang SF, Yueh YY, Chow L, Chien LJ, Chin C, Yang HH, Lin TH, Huang JH.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130672

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Potential Dengue Virus-Triggered Apoptotic Pathway in Human Neuroblastoma Cells: Arachidonic Acid, Superoxide Anion, and NF-[kappa]B Are Sequentially Involved. by Jan JT, Chen BH, Ma SH, Liu CI, Tsai HP, Wu HC, Jiang SY, Yang KD, Shaio MF.; 2000 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116379

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Predominance of HLA-Restricted Cytotoxic T-Lymphocyte Responses to SerotypeCross-Reactive Epitopes on Nonstructural Proteins following Natural Secondary Dengue Virus Infection. by Mathew A, Kurane I, Green S, Stephens HA, Vaughn DW,

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Kalayanarooj S, Suntayakorn S, Chandanayingyong D, Ennis FA, Rothman AL.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=109627 •

Quantitative Competitive Reverse Transcription-PCR for Quantification of Dengue Virus RNA. by Wang WK, Lee CN, Kao CL, Lin YL, King CC.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87378

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Rapid Detection and Quantification of RNA of Ebola and Marburg Viruses, Lassa Virus, Crimean-Congo Hemorrhagic Fever Virus, Rift Valley Fever Virus, Dengue Virus, and Yellow Fever Virus by Real-Time Reverse Transcription-PCR. by Drosten C, Gottig S, Schilling S, Asper M, Panning M, Schmitz H, Gunther S.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120575

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Rapid Subtyping of Dengue Virus Serotypes 1 and 4 by Restriction Site-Specific PCR. by Miagostovich MP, dos Santos FB, Gutierrez CM, Riley LW, Harris E.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88609

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Recombinant Chimeric Yellow Fever-Dengue Type 2 Virus Is Immunogenic and Protective in Nonhuman Primates. by Guirakhoo F, Weltzin R, Chambers TJ, Zhang ZX, Soike K, Ratterree M, Arroyo J, Georgakopoulos K, Catalan J, Monath TP.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112032

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Release of Vasoactive Cytokines by Antibody-Enhanced Dengue Virus Infection of a Human Mast Cell/Basophil Line. by King CA, Marshall JS, Alshurafa H, Anderson R.; 2000 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112233

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RNA Silencing of Dengue Virus Type 2 Replication in Transformed C6/36 Mosquito Cells Transcribing an Inverted-Repeat RNA Derived from the Virus Genome. by Adelman ZN, Sanchez-Vargas I, Travanty EA, Carlson JO, Beaty BJ, Blair CD, Olson KE.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136701

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Serological Differentiation of Infections with Dengue Virus Serotypes 1 to 4 by Using Recombinant Antigens. by Ludolfs D, Schilling S, Altenschmidt J, Schmitz H.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139635

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Serotype-Cross-Reactive Immunoglobulin M Responses in Dengue Virus Infections Determined by Enzyme-Linked Immunosorbent Assay. by Nawa M, Yamada KI, Takasaki T, Akatsuka T, Kurane I.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95954

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Study of Dengue Virus Infection in SCID Mice Engrafted with Human K562 Cells. by Lin YL, Liao CL, Chen LK, Yeh CT, Liu CI, Ma SH, Huang YY, Huang YL, Kao CL, King CC.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110483

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Tick-Borne Langat/Mosquito-Borne Dengue Flavivirus Chimera, a Candidate Live Attenuated Vaccine for Protection against Disease Caused by Members of the TickBorne Encephalitis Virus Complex: Evaluation in Rhesus Monkeys and in Mosquitoes. by Pletnev AG, Bray M, Hanley KA, Speicher J, Elkins R.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115070

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Total Immunoglobulin E Levels and Dengue Infection on San Andres Island, Colombia. by Miguez-Burbano MJ, Jaramillo CA, Palmer CJ, Shor-Posner G, Velasquez LS, Lai H, Baum MK.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95741

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Typing of Dengue Viruses in Clinical Specimens and Mosquitoes by Single-Tube Multiplex Reverse Transcriptase PCR. by Harris E, Roberts TG, Smith L, Selle J, Kramer LD, Valle S, Sandoval E, Balmaseda A.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105176

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Use of Recombinant Envelope Proteins for Serological Diagnosis of Dengue Virus Infection in an Immunochromatographic Assay. by Cuzzubbo AJ, Endy TP, Nisalak A, Kalayanarooj S, Vaughn DW, Ogata SA, Clements DE, Devine PL.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96242

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Virus Replication and Cytokine Production in Dengue Virus-Infected Human B Lymphocytes. by Lin YW, Wang KJ, Lei HY, Lin YS, Yeh TM, Liu HS, Liu CC, Chen SH.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136880

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Widespread intra-serotype recombination in natural populations of dengue virus. by Worobey M, Rambaut A, Holmes EC.; 1999 Jun 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22089

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Yellow Fever Virus/Dengue-2 Virus and Yellow Fever Virus/Dengue-4 Virus Chimeras: Biological Characterization, Immunogenicity, and Protection against Dengue Encephalitis in the Mouse Model. by Chambers TJ, Liang Y, Droll DA, Schlesinger JJ, Davidson AD, Wright PJ, Jiang X.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149507

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with dengue fever, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “dengue fever” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for dengue fever (hyperlinks lead to article summaries): A case report: intracranial haemorrhage in a patient with probable dengue fever.

6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A case report: intracranial haemorrhage in a patient with probable dengue fever. Author(s): Wafa SR, Jamsari S, Karis BM. Source: Med J Malaysia. 1999 June; 54(2): 273-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10972043&dopt=Abstract

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A clinical, serological, and immunological study in a Japanese traveler with dengue fever. Author(s): Kurane I. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2002 December; 8(4): 378. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525905&dopt=Abstract

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A clinical, serological, and immunological study in a Japanese traveler with dengue fever. Author(s): Masaki H, Hasebe F, Ahmed K, Fukuda T, Furumoto A, Watanabe K, Oishi K, Igarashi A, Nagatake T. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2002 December; 8(4): 365-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525901&dopt=Abstract

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A comparison of the pattern of liver involvement in dengue hemorrhagic fever with classic dengue fever. Author(s): Wahid SF, Sanusi S, Zawawi MM, Ali RA. Source: Southeast Asian J Trop Med Public Health. 2000 June; 31(2): 259-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11127322&dopt=Abstract

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A focal, rapidly-controlled outbreak of dengue fever in two suburbs in Townsville, north Queensland, 2001. Author(s): Hills SL, Piispanen JP, Humphreys JL, Foley PN. Source: Commun Dis Intell. 2002; 26(4): 596-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12549533&dopt=Abstract

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A Japanese case of dengue fever with lymphocytic vasculitis: diagnosis by polymerase chain reaction. Author(s): Ishikawa H, Okada S, Katayama I, Mazaki H, Nagatake T, Hasebe F, Igarashi A. Source: The Journal of Dermatology. 1999 January; 26(1): 29-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10063209&dopt=Abstract

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A large epidemic of dengue fever with dengue hemorrhagic cases in Ceara State, Brazil, 1994. Author(s): Vasconcelos PF, de Menezes DB, Melo LP, Pesso ET, Rodrigues SG, da Rosa ES, Timbo MJ, Coelho IC, Montenegro F, da Rosa JF, et al. Source: Revista Do Instituto De Medicina Tropical De Sao Paulo. 1995 May-June; 37(3): 253-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8525272&dopt=Abstract

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A model of the transmission of dengue fever with an evaluation of the impact of ultra-low volume (ULV) insecticide applications on dengue epidemics. Author(s): Newton EA, Reiter P. Source: The American Journal of Tropical Medicine and Hygiene. 1992 December; 47(6): 709-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1361721&dopt=Abstract

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A pandemic of dengue fever on the Hainan Island. Epidemiologic investigations. Author(s): Qiu FX, Zhao ZG. Source: Chinese Medical Journal. 1988 July; 101(7): 463-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3147839&dopt=Abstract

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A retrospective serological study of Japanese who contracted dengue fever in Thailand. Author(s): Fukunaga T, Okuno Y, Tadano M, Fukai K. Source: Biken J. 1983 June; 26(2): 67-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6661173&dopt=Abstract

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A simulation model of the epidemiology of urban dengue fever: literature analysis, model development, preliminary validation, and samples of simulation results. Author(s): Focks DA, Daniels E, Haile DG, Keesling JE. Source: The American Journal of Tropical Medicine and Hygiene. 1995 November; 53(5): 489-506. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7485707&dopt=Abstract

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A tourist with dengue fever and visual loss. Author(s): Haritoglou C, Dotse SD, Rudolph G, Stephan CM, Thurau SR, Klauss V. Source: Lancet. 2002 October 5; 360(9339): 1070. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12383989&dopt=Abstract

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Acalculous cholecystitis as an atypical presentation of dengue fever. Author(s): Sood A, Midha V, Sood N, Kaushal V. Source: The American Journal of Gastroenterology. 2000 November; 95(11): 3316-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11095371&dopt=Abstract

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Acute disseminated encephalomyelitis following dengue fever. Author(s): Yamamoto Y, Takasaki T, Yamada K, Kimura M, Washizaki K, Yoshikawa K, Hitani A, Nakamura T, Iwamoto A. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2002 June; 8(2): 175-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111572&dopt=Abstract

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Acute renal failure associated with dengue fever in French Guiana. Author(s): Hommel D, Talarmin A, Reynes JM, Hulin A. Source: Nephron. 1999; 83(2): 183. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10516508&dopt=Abstract

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Aedes aegypti in a Texas coastal county as an index of dengue fever receptivity and control. Author(s): Micks DW, Moon WB. Source: The American Journal of Tropical Medicine and Hygiene. 1980 November; 29(6): 1382-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6160776&dopt=Abstract

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An epidemic of Dengue fever in Karachi--associated clinical manifestations. Author(s): Qureshi JA, Notta NJ, Salahuddin N, Zaman V, Khan JA. Source: J Pak Med Assoc. 1997 July; 47(7): 178-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9301157&dopt=Abstract

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An epidemic of dengue fever in Wewak. Author(s): Farrell KT. Source: P N G Med J. 1978 June; 21(2): 191-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=279165&dopt=Abstract

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An insular outbreak of dengue fever in a rural south Indian village. Author(s): Norman G, Theodre A, Joseph A. Source: J Commun Dis. 1991 September; 23(3): 185-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1812164&dopt=Abstract

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An investigation into the cyclical incidence of dengue fever. Author(s): Keating J. Source: Social Science & Medicine (1982). 2001 December; 53(12): 1587-97. Erratum In: Soc Sci Med 2002 November; 55(9): 1691. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11762885&dopt=Abstract

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An outbreak of dengue fever in rural areas of northern India. Author(s): Kumar A, Sharma SK, Padbidri VS, Thakare JP, Jain DC, Datta KK. Source: J Commun Dis. 2001 December; 33(4): 274-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12561505&dopt=Abstract

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An outbreak of type 1 dengue fever on Grande Comore island. Author(s): Morvan JM, Boisier P, Laventure S, Roux JJ, Charrier N, Martin E. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1994 May; 84(5): 298. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7809791&dopt=Abstract

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An outbreak of type 2 dengue fever in the Seychelles, probably transmitted by Aedes albopictus (Skuse). Author(s): Metselaar D, Grainger CR, Oei KG, Reynolds DG, Pudney M, Leake CJ, Tukei PM, D'Offay RM, Simpson DI. Source: Bulletin of the World Health Organization. 1980; 58(6): 937-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6971192&dopt=Abstract

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An update on Dengue fever in the Caribbean. Author(s): Hospedales CJ. Source: The West Indian Medical Journal. 1990 June; 39(2): 131. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2402899&dopt=Abstract

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Antibody responses of dengue fever patients to dengue 2 (New Guinea C strain) viral proteins. Author(s): AbuBakar S, Azmi A, Mohamed-Saad N, Shafee N, Chee HY. Source: Malays J Pathol. 1997 June; 19(1): 41-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10879241&dopt=Abstract

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Antibody responses to an immunodominant nonstructural 1 synthetic peptide in patients with dengue fever and dengue hemorrhagic fever. Author(s): Huang JH, Wey JJ, Sun YC, Chin C, Chien LJ, Wu YC. Source: Journal of Medical Virology. 1999 January; 57(1): 1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9890415&dopt=Abstract

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Bioelectrical impedance spectroscopy in health and disease. Correspondence between whole body and segmental bioelectrical impedance spectroscopy indices in patients with classical dengue fever. Author(s): Mazariegos M, Klassen P, Solomons NW, Furst P. Source: Annals of the New York Academy of Sciences. 2000 May; 904: 205-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10865740&dopt=Abstract

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Brain involvement in Dengue fever. Author(s): Angibaud G, Luaute J, Laille M, Gaultier C. Source: Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. 2001 January; 8(1): 63-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11148085&dopt=Abstract

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Changing epidemiology of dengue fever in travelers to Thailand. Author(s): Schwartz E, Moskovitz A, Potasman I, Peri G, Grossman Z, Alkan ML. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2000 October; 19(10): 7846. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11117644&dopt=Abstract

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Characterisation of lymphocyte response and cytokine patterns in patients with dengue fever. Author(s): Azeredo EL, Zagne SM, Santiago MA, Gouvea AS, Santana AA, Neves-Souza PC, Nogueira RM, Miagostovich MP, Kubelka CF. Source: Immunobiology. 2001 December; 204(4): 494-507. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11776403&dopt=Abstract

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Clinical & virological study of dengue fever outbreak in Jalore city, Rajasthan 1985. Author(s): Chouhan GS, Rodrigues FM, Shaikh BH, Ilkal MA, Khangaro SS, Mathur KN, Joshi KR, Vaidhye NK. Source: The Indian Journal of Medical Research. 1990 November; 91: 414-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2091986&dopt=Abstract

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Clinical observations of virologically confirmed dengue fever in the 1987 outbreak in southern Taiwan. Author(s): Liu HW, Ho TL, Hwang CS, Liao YH. Source: Gaoxiong Yi Xue Ke Xue Za Zhi. 1989 January; 5(1): 42-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2733066&dopt=Abstract

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Clinical spectrum of dengue fever in travellers. Author(s): Mills GD, Jones PD. Source: N Z Med J. 1991 June 12; 104(913): 228-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2052229&dopt=Abstract

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Comparative evaluation of various commercial assays for diagnosis of dengue fever. Author(s): Vajpayee M, Singh UB, Seth P, Broor S. Source: Southeast Asian J Trop Med Public Health. 2001 September; 32(3): 472-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11944701&dopt=Abstract

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Comparison of PanBio dengue duo enzyme-linked immunosorbent assay (ELISA) and MRL dengue fever virus immunoglobulin M capture ELISA for diagnosis of dengue virus infections in Southeast Asia. Author(s): Cuzzubbo AJ, Vaughn DW, Nisalak A, Solomon T, Kalayanarooj S, Aaskov J, Dung NM, Devine PL. Source: Clinical and Diagnostic Laboratory Immunology. 1999 September; 6(5): 705-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10473522&dopt=Abstract

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Competitive exclusion in a vector-host model for the dengue fever. Author(s): Feng Z, Velasco-Hernandez JX. Source: Journal of Mathematical Biology. 1997 May; 35(5): 523-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9145954&dopt=Abstract

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Complement pathway activity in serum from patients with classical dengue fever. Author(s): Shaio MF, Chang FY, Hou SC. Source: Trans R Soc Trop Med Hyg. 1992 November-December; 86(6): 672-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1287942&dopt=Abstract

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Computer simulations to predict the availability of peptides with known HLA class I motifs generated by proteolysis of dengue fever virus (DFV) type 1 structural and nonstructural proteins in infected cells. Author(s): Becker Y. Source: Virus Genes. 1995; 10(3): 195-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8560780&dopt=Abstract

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Control of dengue fever with active surveillance and the use of insecticidal aerosol cans. Author(s): Osaka K, Ha DQ, Sakakihara Y, Khiem HB, Umenai T. Source: Southeast Asian J Trop Med Public Health. 1999 September; 30(3): 484-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10774656&dopt=Abstract

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Control of haemorrhagic dengue fever (HDF). Author(s): Farid MA. Source: Acta Med Philipp. 1967 January-March; 3(3): 201-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6038218&dopt=Abstract

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Culture-amplified detection of dengue virus from serum in an outbreak of dengue fever. Author(s): Gleeson F, McBride J, Norton R. Source: Journal of Medical Virology. 1999 February; 57(2): 212-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9892410&dopt=Abstract

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Decrease in human immunodeficiency virus type 1 load during acute dengue fever. Author(s): Watt G, Kantipong P, Jongsakul K. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 April 15; 36(8): 1067-9. Epub 2003 Apr 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684921&dopt=Abstract

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Dengue fever among Swedish tourists. Author(s): Wittesjo B, Eitrem R, Niklasson B. Source: Scandinavian Journal of Infectious Diseases. 1993; 25(6): 699-704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8052809&dopt=Abstract

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Dengue fever among travelers. Author(s): Schwartz E, Mendelson E, Sidi Y. Source: The American Journal of Medicine. 1996 November; 101(5): 516-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8948275&dopt=Abstract

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Dengue fever and dengue haemorrhagic fever in Malaysia. Author(s): Cardosa MJ. Source: Southeast Asian J Trop Med Public Health. 1988 September; 19(3): 483-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3217825&dopt=Abstract

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Dengue fever and dengue haemorrhagic fever. Author(s): John TJ. Source: Lancet. 2003 January 11; 361(9352): 181-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531616&dopt=Abstract

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Dengue fever and dengue haemorrhagic fever: challenges of controlling an enemy still at large. Author(s): Kurane I, Takasaki T. Source: Reviews in Medical Virology. 2001 September-October; 11(5): 301-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11590668&dopt=Abstract

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Dengue fever and dengue shock syndrome in French Polynesia. Author(s): Glaziou P, Chungue E, Gestas P, Soulignac O, Couter JP, Plichart R, Roux JF, Poli L. Source: Southeast Asian J Trop Med Public Health. 1992 September; 23(3): 531-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1488712&dopt=Abstract

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Dengue fever and dengue shock syndrome. Author(s): Morens DM. Source: Hosp Pract (Off Ed). 1982 July; 17(7): 103-7, 110-3. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6125466&dopt=Abstract

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Dengue fever and El Nino. Author(s): Sehgal R. Source: Lancet. 1997 March 8; 349(9053): 729. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9078222&dopt=Abstract

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Dengue fever associated with a haematoma of the rectus abdominis muscle. Author(s): Ganeshwaran Y, Seneviratne SM, Jayamaha R, De Silva AP, Balasuriya WK. Source: Ceylon Med J. 2001 September; 46(3): 105-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11732298&dopt=Abstract

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Dengue fever complicated by pulmonary haemorrhage manifesting as haemoptysis. Author(s): Liam CK, Yap BH, Lam SK. Source: J Trop Med Hyg. 1993 June; 96(3): 197-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8505777&dopt=Abstract

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Dengue fever epidemic in Chennai--a study of clinical profile and outcome. Author(s): Narayanan M, Aravind MA, Thilothammal N, Prema R, Sargunam CS, Ramamurty N. Source: Indian Pediatrics. 2002 November; 39(11): 1027-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466573&dopt=Abstract

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Dengue fever epidemic potential as projected by general circulation models of global climate change. Author(s): Patz JA, Martens WJ, Focks DA, Jetten TH. Source: Environmental Health Perspectives. 1998 March; 106(3): 147-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9452414&dopt=Abstract

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Dengue fever epidemics in the South Pacific: driven by El Nino Southern Oscillation? Author(s): Hales S, Weinstein P, Woodward A. Source: Lancet. 1996 December 14; 348(9042): 1664-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8962017&dopt=Abstract

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Dengue fever imported from India. A report of 3 cases. Author(s): Blackburn NK, Rawat R. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1987 March 21; 71(6): 386-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3563775&dopt=Abstract

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Dengue fever in a Puerto Rican community. Author(s): Neff JM, Morris L, Gonzalez-Alcover R, Coleman PH, Lyss SB, Negron H. Source: American Journal of Epidemiology. 1967 July; 86(1): 162-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4951556&dopt=Abstract

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Dengue fever in a Western United States City. Author(s): Schleupner CJ. Source: The Western Journal of Medicine. 1977 August; 127(2): 145-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=898946&dopt=Abstract

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Dengue fever in American military personnel in the Philippines: clinical observations on hospitalized patients during a 1984 epidemic. Author(s): Hayes CG, O'Rourke TF, Fogelman V, Leavengood DD, Crow G, Albersmeyer MM. Source: Southeast Asian J Trop Med Public Health. 1989 March; 20(1): 1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2772694&dopt=Abstract

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Dengue fever in Brazilian adults and children: assessment of clinical findings and their validity for diagnosis. Author(s): Nunes-Araujo FR, Ferreira MS, Nishioka SD. Source: Annals of Tropical Medicine and Parasitology. 2003 June; 97(4): 415-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12831527&dopt=Abstract

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Dengue fever in Canada. Author(s): McCarthy MA, Carpenter D, Goyette M, Nguyen DT. Source: Can Commun Dis Rep. 1995 October 30; 21(20): 185-7. English, French. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8563691&dopt=Abstract

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Dengue fever in India. Author(s): Rao CV. Source: Indian J Pediatr. 1987 January-February; 54(1): 11-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3557581&dopt=Abstract

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Dengue fever in international travelers. Author(s): Jelinek T. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2000 July; 31(1): 144-7. Epub 2000 July 26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10913412&dopt=Abstract

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Dengue fever in Jamaica with shock and hypocomplementaemia, haemorrhagic, visceral and neurological complications. Author(s): Fraser HS, Wilson WA, Rose E, Thomas EJ, Sissons JG. Source: The West Indian Medical Journal. 1978 June; 27(2): 106-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=695551&dopt=Abstract

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Dengue fever in mid-Missouri. A case report. Author(s): Chan-Tack KM. Source: Mo Med. 2002 June; 99(6): 259-61. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12085693&dopt=Abstract

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Dengue fever in returned travellers. Author(s): Read K, Ellis-Pegler RB. Source: N Z Med J. 2001 April 27; 114(1130): 194. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11396673&dopt=Abstract

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Dengue fever in the Caribbean. Author(s): Hospedales CJ. Source: The West Indian Medical Journal. 1990 March; 39(1): 59-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2185596&dopt=Abstract

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Dengue fever in the Czech Republic. Author(s): Chalupa P, Kubek J, Hejlova A. Source: Bratisl Lek Listy. 2001; 102(7): 322-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11725386&dopt=Abstract

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Dengue fever in the United States. A report of a cluster of imported cases and review of the clinical, epidemiologic, and public health aspects of the disease. Author(s): Malison MD, Waterman SH. Source: Jama : the Journal of the American Medical Association. 1983 January 28; 249(4): 496-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6848850&dopt=Abstract

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Dengue fever in the Western Hemisphere. Author(s): Castleberry JS, Mahon CR. Source: Clin Lab Sci. 2003 Winter; 16(1): 34-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587656&dopt=Abstract

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Dengue fever in travelers to the tropics, 1998 and 1999. Author(s): Lindback H, Lindback J, Tegnell A, Janzon R, Vene S, Ekdahl K. Source: Emerging Infectious Diseases. 2003 April; 9(4): 438-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702223&dopt=Abstract

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Dengue fever in U.S. troops during Operation Restore Hope, Somalia, 1992-1993. Author(s): Sharp TW, Wallace MR, Hayes CG, Sanchez JL, DeFraites RF, Arthur RR, Thornton SA, Batchelor RA, Rozmajzl PJ, Hanson RK, et al. Source: The American Journal of Tropical Medicine and Hygiene. 1995 July; 53(1): 89-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7625541&dopt=Abstract

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Dengue fever in US military personnel in Haiti. Author(s): Trofa AF, DeFraites RF, Smoak BL, Kanesa-thasan N, King AD, Burrous JM, MacArthy PO, Rossi C, Hoke CH Jr. Source: Jama : the Journal of the American Medical Association. 1997 May 21; 277(19): 1546-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9153369&dopt=Abstract

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Dengue fever mimicking plasma cell leukemia. Author(s): Gawoski JM, Ooi WW. Source: Archives of Pathology & Laboratory Medicine. 2003 August; 127(8): 1026-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873179&dopt=Abstract

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Dengue fever on the increase. Author(s): Dove A. Source: Nature Medicine. 1998 May; 4(5): 543. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9585216&dopt=Abstract

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Dengue fever outbreaks in two villages of Dharmapuri district in Tamil Nadu. Author(s): Victor TJ, Malathi M, Gurusamy D, Desai A, Ravi V, Narayanasamy G, Anuradha L, Rani C, Krishnamurthy P. Source: The Indian Journal of Medical Research. 2002 October; 116: 133-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12674826&dopt=Abstract

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Dengue fever risk and prevention for short-term group travelers to tropical regions. Author(s): Norwood CG, Larocco A, Laravia DA, Moore RW, Pittman-Cooley L. Source: J La State Med Soc. 1999 June; 151(6): 313-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12001919&dopt=Abstract

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Dengue fever threat. Author(s): Ewing T. Source: Nature. 1988 May 26; 333(6171): 291. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3374561&dopt=Abstract

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Dengue fever virus and Japanese encephalitis virus synthetic peptides, with motifs to fit HLA class I haplotypes prevalent in human populations in endemic regions, can be used for application to skin Langerhans cells to prime antiviral CD8+ cytotoxic T cells (CTLs)--a novel approach to the protection of humans. Author(s): Becker Y. Source: Virus Genes. 1994 September; 9(1): 33-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7871759&dopt=Abstract

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Dengue fever with acute acalculous cholecystitis. Author(s): Wu KL, Changchien CS, Kuo CM, Chuah SK, Lu SN, Eng HL, Kuo CH. Source: The American Journal of Tropical Medicine and Hygiene. 2003 June; 68(6): 65760. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12887023&dopt=Abstract

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Dengue fever with encephalopathy in Australia. Author(s): Row D, Weinstein P, Murray-Smith S. Source: The American Journal of Tropical Medicine and Hygiene. 1996 March; 54(3): 253-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8600760&dopt=Abstract

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Dengue fever with hemorrhagic manifestations: a report of three cases from Puerto Rico. Author(s): Lopez-Correa RH, Cline BL, Ramirez-Ronda C, Bermudez R, Sather GE, Kuno G. Source: The American Journal of Tropical Medicine and Hygiene. 1978 November; 27(6): 1216-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=727327&dopt=Abstract

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Dengue fever with non-classical symptoms (survey of anti-dengue antibodies from patients admitted to the Dr. Tjipto Mangunkusumo Hospital, Jakarta). Author(s): Pelenkahu TB, Pudjiadi SH, Samsudin, Siahaan CM, Moeljono SP, Saroso JS, Purnama B, Thaib S. Source: Paediatr Indones. 1972 January; 12(1): 15-20. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5032316&dopt=Abstract

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Dengue fever with thrombocytopenia: studies towards defining vulnerability of bleeding. Author(s): Garcia S, Morales R, Hunter RF. Source: Bol Asoc Med P R. 1995 January-February; 87(1-2): 2-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7786355&dopt=Abstract

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Dengue fever. Author(s): Waterman SH, Gubler DJ. Source: Clinics in Dermatology. 1989 January-March; 7(1): 117-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2647259&dopt=Abstract

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Dengue fever. Author(s): Payling KJ. Source: Prof Nurse. 1997 April; 12(7): 507-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9155462&dopt=Abstract

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Dengue fever. Author(s): Hennessy WB. Source: The Medical Journal of Australia. 1979 June 30; 1(13): 622. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=492017&dopt=Abstract

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Dengue fever. Author(s): Black RH. Source: The Medical Journal of Australia. 1977 July 16; 2(3): 75-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=19690&dopt=Abstract

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Dengue fever. An Australian perspective. Author(s): McBride JH. Source: Aust Fam Physician. 1999 April; 28(4): 319-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10330754&dopt=Abstract

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Dengue fever. Reappearance in northern Queensland after 26 years. Author(s): Kay BH, Barker-Hudson P, Stallman ND, Wiemers MA, Marks EN, Holt PJ, Muscio M, Gorman BM. Source: The Medical Journal of Australia. 1984 March 3; 140(5): 264-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6700459&dopt=Abstract

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Dengue fever. Role of nursing personnel. Author(s): Nandi M. Source: The Nursing Journal of India. 1996 November; 87(11): 252. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9096490&dopt=Abstract

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Dengue fever. Some basic facts. Author(s): Innocentia Sister. Source: The Nursing Journal of India. 1997 February; 88(2): 26-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9287725&dopt=Abstract

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Dengue fever/dengue haemorrhagic fever in Filipino children: clinical experience during the 1983-1984 epidemic. Author(s): Songco RS, Hayes CG, Leus CD, Manaloto CO. Source: Southeast Asian J Trop Med Public Health. 1987 September; 18(3): 284-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3433159&dopt=Abstract

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Dengue fever: a harmful disease in patients with thrombocytopenia? Author(s): Strobel M, Muller P, Lamaury I, Rouet F. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 August 15; 33(4): 580-1. Epub 2001 July 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11462200&dopt=Abstract

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Dengue fever: a resurgent risk for the international traveler. Author(s): Lange WR, Beall B, Denny SC. Source: American Family Physician. 1992 March; 45(3): 1161-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1543101&dopt=Abstract

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Dengue fever: a risk to travelers. Author(s): Karp BE. Source: Md Med J. 1997 July; 46(6): 299-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9579202&dopt=Abstract

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Dengue NS1-specific antibody responses: isotype distribution and serotyping in patients with Dengue fever and Dengue hemorrhagic fever. Author(s): Shu PY, Chen LK, Chang SF, Yueh YY, Chow L, Chien LJ, Chin C, Lin TH, Huang JH. Source: Journal of Medical Virology. 2000 October; 62(2): 224-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11002252&dopt=Abstract

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Dengue virus in the brain of a fatal case of hemorrhagic dengue fever. Author(s): Ramos C, Sanchez G, Pando RH, Baquera J, Hernandez D, Mota J, Ramos J, Flores A, Llausas E. Source: Journal of Neurovirology. 1998 August; 4(4): 465-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9718141&dopt=Abstract

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Detection of circulant tumor necrosis factor-alpha, soluble tumor necrosis factor p75 and interferon-gamma in Brazilian patients with dengue fever and dengue hemorrhagic fever. Author(s): Braga EL, Moura P, Pinto LM, Ignacio SR, Oliveira MJ, Cordeiro MT, Kubelka CF. Source: Memorias Do Instituto Oswaldo Cruz. 2001 February; 96(2): 229-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11285501&dopt=Abstract

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Detection of IgM antibodies from cerebrospinal fluid and sera of dengue fever patients. Author(s): Chen WJ, Hwang KP, Fang AH. Source: Southeast Asian J Trop Med Public Health. 1991 December; 22(4): 659-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1820657&dopt=Abstract

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Development of new vaccines against dengue fever and Japanese encephalitis. Author(s): Kinney RM, Huang CY. Source: Intervirology. 2001; 44(2-3): 176-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11509879&dopt=Abstract

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Don't forget dengue! Clinical features of dengue fever in returning travellers. Author(s): Shirtcliffe P, Cameron E, Nicholson KG, Wiselka MJ. Source: Journal of the Royal College of Physicians of London. 1998 May-June; 32(3): 2357. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9670150&dopt=Abstract

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Dot enzyme immunoassay: an alternative diagnostic aid for dengue fever and dengue haemorrhagic fever. Author(s): Cardosa MJ, Tio PH. Source: Bulletin of the World Health Organization. 1991; 69(6): 741-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1786623&dopt=Abstract

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Effects of dengue fever during pregnancy in French Guiana. Author(s): Carles G, Peiffer H, Talarmin A. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1999 March; 28(3): 637-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10194092&dopt=Abstract

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Elevated tumour necrosis factor in dengue fever and dengue haemorrhagic fever. Author(s): Vitarana T, de Silva H, Withana N, Gunasekera C. Source: Ceylon Med J. 1991 June; 36(2): 63-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1913986&dopt=Abstract

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Entomological investigations during outbreaks of dengue fever in certain villages in Maharashtra state. Author(s): Ilkal MA, Dhanda V, Hassan MM, Mavale M, Mahadev PV, Shetty PS, Guttikar SN, Banerjee K. Source: The Indian Journal of Medical Research. 1991 May; 93: 174-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1937596&dopt=Abstract

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Epidemic dengue fever caused by dengue type 2 virus in Kenya: preliminary results of human virological and serological studies. Author(s): Johnson BK, Ocheng D, Gichogo A, Okiro M, Libondo D, Kinyanjui P, Tukei PM. Source: East Afr Med J. 1982 December; 59(12): 781-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7184757&dopt=Abstract

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Epidemic dengue fever in Puerto Rico, 1977: a cost analysis. Author(s): Von Allmen SD, Lopez-Correa RH, Woodall JP, Morens DM, Chiriboga J, Casta-Velez A. Source: The American Journal of Tropical Medicine and Hygiene. 1979 November; 28(6): 1040-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=507281&dopt=Abstract

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Epidemic of fever of unknown origin in rural Thailand, caused by influenza A (H1N1) and dengue fever. Author(s): Silarug N, Foy HM, Kupradinon S, Rojanasuphot S, Nisalak A, Pongsuwant Y. Source: Southeast Asian J Trop Med Public Health. 1990 March; 21(1): 61-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2169651&dopt=Abstract

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Epidemiological aspects of an outbreak of dengue fever/dengue haemorrhagic fever in Singapore. Author(s): Goh KT, Ng SK, Chan YC, Lim SJ, Chua EC. Source: Southeast Asian J Trop Med Public Health. 1987 September; 18(3): 295-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3433161&dopt=Abstract

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Epidemiology and clinical features of imported dengue fever in Europe: sentinel surveillance data from TropNetEurop. Author(s): Jelinek T, Muhlberger N, Harms G, Corachan M, Grobusch MP, Knobloch J, Bronner U, Laferl H, Kapaun A, Bisoffi Z, Clerinx J, Puente S, Fry G, Schulze M, Hellgren U, Gjorup I, Chalupa P, Hatz C, Matteelli A, Schmid M, Nielsen LN, da Cunha S, Atouguia J, Myrvang B, Fleischer K; European Network on Imported Infectious Disease Surveillance. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 November 1; 35(9): 1047-52. Epub 2002 October 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384837&dopt=Abstract

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Epidemiology of dengue/dengue hemorrhagic fever in Malaysia--a retrospective epidemiological study. 1973-1987. Part II: Dengue fever (DF). Author(s): Shekhar KC, Huat OL. Source: Asia Pac J Public Health. 1992-93; 6(3): 126-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1342799&dopt=Abstract

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Etiologic and serologic investigations of the 1980 epidemic of dengue fever on Hainan Island, China. Author(s): Li FS, Yang FR, Song JC, Gao H, Tang JQ, Zou CH, Hu BN, Wen SR, Qiu FX. Source: The American Journal of Tropical Medicine and Hygiene. 1986 September; 35(5): 1051-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3766851&dopt=Abstract

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Evaluation of ELISA-based sero-diagnosis of dengue fever in travelers. Author(s): Schwartz E, Mileguir F, Grossman Z, Mendelson E. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2000 December; 19(3): 169-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11090753&dopt=Abstract

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Evaluation of the MRL diagnostics dengue fever virus IgM capture ELISA and the PanBio Rapid Immunochromatographic Test for diagnosis of dengue fever in Jamaica. Author(s): Palmer CJ, King SD, Cuadrado RR, Perez E, Baum M, Ager AL. Source: Journal of Clinical Microbiology. 1999 May; 37(5): 1600-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10203534&dopt=Abstract

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Field epidemiology of an outbreak of dengue fever in Charters Towers, Queensland: are insect screens protective? Author(s): Murray-Smith S, Weinstein P, Skelly C. Source: Aust N Z J Public Health. 1996 October; 20(5): 545-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8987228&dopt=Abstract

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First confirmed dengue-1 fever cases reported from Cameroon. Author(s): Krippner R, von Laer G. Source: Journal of Travel Medicine : Official Publication of the International Society of Travel Medicine and the Asia Pacific Travel Health Association. 2002 SeptemberOctober; 9(5): 273-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12962604&dopt=Abstract

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First outbreak of Dengue fever in a typical rural area of Haryana state in northern India. Author(s): Jamaluddain M, Saxena VK. Source: J Commun Dis. 1997 June; 29(2): 169-70. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9282518&dopt=Abstract

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First reported outbreak of classical dengue fever at 1,700 meters above sea level in Guerrero State, Mexico, June 1988. Author(s): Herrera-Basto E, Prevots DR, Zarate ML, Silva JL, Sepulveda-Amor J. Source: The American Journal of Tropical Medicine and Hygiene. 1992 June; 46(6): 64953. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1621889&dopt=Abstract

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Fluid intake and decreased risk for hospitalization for dengue fever, Nicaragua. Author(s): Harris E, Perez L, Phares CR, Perez Mde L, Idiaquez W, Rocha J, Cuadra R, Hernandez E, Campos LA, Gonzales A, Amador JJ, Balmaseda A. Source: Emerging Infectious Diseases. 2003 August; 9(8): 1003-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12967502&dopt=Abstract

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Hydrational status assessed by bioelectrical impedance spectroscopy and dilution methods in patients with classical dengue fever. Author(s): Klassen P, Mazariegos M, Deurenberg P, Solomons NW, Furst P. Source: Annals of the New York Academy of Sciences. 2000 May; 904: 163-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10865731&dopt=Abstract

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Immunoglobulin A-specific capture enzyme-linked immunosorbent assay for diagnosis of dengue fever. Author(s): Talarmin A, Labeau B, Lelarge J, Sarthou JL. Source: Journal of Clinical Microbiology. 1998 May; 36(5): 1189-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9574674&dopt=Abstract

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Immunological studies with group B arthropod-borne viruses. V. Evaluation of crossimmunity against type 1 dengue fever in human subjects convalescent from subclinical natural Japanese encephalitis virus infection and vaccinated with 17D strain yellow fever vaccine. Author(s): Wisseman CL Jr, Kitaoka M, Tamiya T. Source: The American Journal of Tropical Medicine and Hygiene. 1966 July; 15(4): 588600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4287392&dopt=Abstract

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Imported dengue fever in New York State. Author(s): Srihongse S, Deibel R, Sather GE, Woodall JP. Source: N Y State J Med. 1982 June; 82(7): 1057-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6955640&dopt=Abstract

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Incidence of dengue fever in relation to climatic factors in Ludhiana, Punjab. Author(s): Ram S, Khurana S, Kaushal V, Gupta R, Khurana SB. Source: The Indian Journal of Medical Research. 1998 October; 108: 128-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9805841&dopt=Abstract

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Increased pro-inflammatory cytokines (TNF-alpha and IL-6) and anti-inflammatory compounds (sTNFRp55 and sTNFRp75) in Brazilian patients during exanthematic dengue fever. Author(s): Pinto LM, Oliveira SA, Braga EL, Nogueira RM, Kubelka CF. Source: Memorias Do Instituto Oswaldo Cruz. 1999 May-June; 94(3): 387-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10348988&dopt=Abstract

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Infectious diseases of refugees and immigrants: dengue fever. Author(s): Roberts A, Kemp C. Source: Journal of the American Academy of Nurse Practitioners. 2001 June; 13(6): 243-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11930865&dopt=Abstract

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Investigations on the outbreak of dengue fever in Ajmer City, Rajasthan in 1969. Part II: Result of serological tests. Author(s): Ghosh SN, Sheikh BH. Source: The Indian Journal of Medical Research. 1974 April; 62(4): 523-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4435862&dopt=Abstract

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Investigations on the outbreak of dengue fever in Ajmer City, Rajasthan State in 1969. Part I. Epidemiological, clinical and virological study of the epidemic. Author(s): Ghosh SN, Pavri KM, Singh KR, Sheikh BH, D'lima LV, Mahadev PV, Ramachandra Rao T. Source: The Indian Journal of Medical Research. 1974 April; 62(4): 511-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4435861&dopt=Abstract

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Involvement of the central nervous system in dengue fever: three serologically confirmed cases from Fortaleza Ceara, Brazil. Author(s): Vasconcelos PF, da Rosa AP, Coelho IC, Menezes DB, da Rosa ES, Rodrigues SG, da Rosa JF. Source: Revista Do Instituto De Medicina Tropical De Sao Paulo. 1998 January-February; 40(1): 35-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9713136&dopt=Abstract

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Isolation and partial characterization of dengue virus type 2 and 4 strains from dengue fever and dengue haemorrhagic fever patients from Mindanao, Republic of the Philippines. Author(s): ter Meulen J, Grau M, Lenz O, Emmerich P, Schmitz H, Oh F, Jaspert R, Niedrig M. Source: Tropical Medicine & International Health : Tm & Ih. 2000 May; 5(5): 325-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10886794&dopt=Abstract

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Isolation and serotyping of dengue viruses by mosquito inoculation technique from clinically suspected cases of dengue fever. Author(s): Pervin M, Tabassum S, Islam MN. Source: Bangladesh Med Res Counc Bull. 2002 December; 28(3): 104-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509382&dopt=Abstract

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Japanese encephalitis vaccine including a preliminary report on dengue fever and Chikungunya vaccines. Author(s): Kitaoka M. Source: Jpn J Med Sci Biol. 1967 December; 20: 41-56. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4297905&dopt=Abstract

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Laboratory diagnosis of acute dengue fever during the United Nations Mission in Haiti, 1995-1996. Author(s): Rossi CA, Drabick JJ, Gambel JM, Sun W, Lewis TE, Henchal EA. Source: The American Journal of Tropical Medicine and Hygiene. 1998 August; 59(2): 275-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9715946&dopt=Abstract

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Lesser known clinical features of dengue fever. Author(s): Adhikari MR, Pereira P, Padbidri VS, Chowta N, Thakare J. Source: J Assoc Physicians India. 1999 December; 47(12): 1168-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11225218&dopt=Abstract

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Liver biochemical tests and dengue fever. Author(s): Kuo CH, Tai DI, Chang-Chien CS, Lan CK, Chiou SS, Liaw YF. Source: The American Journal of Tropical Medicine and Hygiene. 1992 September; 47(3): 265-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1355950&dopt=Abstract

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Liver histopathology and biological correlates in five cases of fatal dengue fever in Vietnamese children. Author(s): Huerre MR, Lan NT, Marianneau P, Hue NB, Khun H, Hung NT, Khen NT, Drouet MT, Huong VT, Ha DQ, Buisson Y, Deubel V. Source: Virchows Archiv : an International Journal of Pathology. 2001 February; 438(2): 107-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11253111&dopt=Abstract

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Low rates of antigen detection and virus isolation from the peripheral blood leukocytes of dengue fever patients. Author(s): Waterman SH, Kuno G, Gubler DJ, Sather GE. Source: The American Journal of Tropical Medicine and Hygiene. 1985 March; 34(2): 380-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3885775&dopt=Abstract

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Low specificity of an immunochromatographic serological assay for diagnosis of dengue Fever in travelers returning with malaria. Author(s): Charrel RN, de Lamballerie X. Source: Clinical and Diagnostic Laboratory Immunology. 2002 November; 9(6): 1400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414786&dopt=Abstract

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Lymphocyte changes in secondary dengue fever: use of the Technicon H*1 to monitor progress of infection. Author(s): Liu TC, Chan YC, Han P. Source: Southeast Asian J Trop Med Public Health. 1991 September; 22(3): 332-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1818382&dopt=Abstract

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Management of dengue fever in ICU. Author(s): Soni A, Chugh K, Sachdev A, Gupta D. Source: Indian J Pediatr. 2001 November; 68(11): 1051-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11770241&dopt=Abstract

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Menorrhagia caused by dengue fever. Author(s): McGready R, Paw E, Nosten F. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2000 August; 40(3): 354-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11065050&dopt=Abstract

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Molecular epidemiology of dengue 3 viruses and genetic relatedness among dengue 3 strains isolated from patients with mild or severe form of dengue fever in French Polynesia. Author(s): Chungue E, Deubel V, Cassar O, Laille M, Martin PM. Source: The Journal of General Virology. 1993 December; 74 ( Pt 12): 2765-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8277284&dopt=Abstract

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Nucleotide and encoded amino acid sequences of the capsid protein gene of three dengue-2 viruses isolated in Malaysia from patients with dengue haemorrhagic fever, dengue shock syndrome or dengue fever. Author(s): Samuel S, Koh CL, Pang T, Lam SK. Source: Nucleic Acids Research. 1990 April 11; 18(7): 1904. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2336373&dopt=Abstract

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Nucleotide and encoded amino acid sequences of the membrane protein precursor and the membrane protein genes of three dengue-2 viruses isolated in Malaysia from patients with dengue haemorrhagic fever, dengue shock syndrome or dengue fever. Author(s): Samuel S, Koh CL, Pang T, Lam SK. Source: Nucleic Acids Research. 1990 April 11; 18(7): 1905. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2336374&dopt=Abstract

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Nucleotide sequence of the envelope protein gene of a Malaysian dengue-2 virus isolated from a patient with dengue fever. Author(s): Samuel S, Koh CL, Blok J, Pang T, Lam SK. Source: Nucleic Acids Research. 1989 November 11; 17(21): 8887. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2587242&dopt=Abstract

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Nucleotide sequences of the nonstructural protein NS1 gene of three dengue-2 viruses, M1, M2 and M3, isolated in Malaysia from patients with dengue haemorrhagic fever, dengue shock syndrome and dengue fever, respectively. Author(s): Fong MY, Koh CL, Samuel S, Pang T, Lam SK. Source: Nucleic Acids Research. 1990 March 25; 18(6): 1642. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2139210&dopt=Abstract

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Observations on dengue fever, benign protector and killer: a Dr. Jekyll and Mr. Hyde. Author(s): Hammon WM. Source: The American Journal of Tropical Medicine and Hygiene. 1969 March; 18(2): 159-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4388466&dopt=Abstract

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Outbreak of Dengue fever in Delhi. Author(s): Acharya SK, Buch P, Irshad M, Gandhi BM, Joshi YK, Tandon BN. Source: Lancet. 1988 December 24-31; 2(8626-8627): 1485-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2904591&dopt=Abstract

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Outbreak of dengue fever in Palau, Western Pacific: risk factors for infection. Author(s): Ashford DA, Savage HM, Hajjeh RA, McReady J, Bartholomew DM, Spiegel RA, Vorndam V, Clark GG, Gubler DG. Source: The American Journal of Tropical Medicine and Hygiene. 2003 August; 69(2): 135-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13677368&dopt=Abstract

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Outbreak of dengue fever in rural areas of Parbhani district of Maharashtra (India). Author(s): Mehendale SM, Risbud AR, Rao JA, Banerjee K. Source: The Indian Journal of Medical Research. 1991 January; 93: 6-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2022403&dopt=Abstract

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Plasmodium falciparum or dengue fever? Author(s): Chakrabarti AK, Das S, Dutta SK. Source: J Assoc Physicians India. 1993 October; 41(10): 687. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8294341&dopt=Abstract

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Platelet transfusion practice during dengue fever epidemic. Author(s): Kumar ND, Tomar V, Singh B, Kela K. Source: Indian J Pathol Microbiol. 2000 January; 43(1): 55-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12583421&dopt=Abstract

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Potential effect of population and climate changes on global distribution of dengue fever: an empirical model. Author(s): Hales S, de Wet N, Maindonald J, Woodward A. Source: Lancet. 2002 September 14; 360(9336): 830-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12243917&dopt=Abstract

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Potential relationship between dengue fever and neural tube defects in a northern district of India. Author(s): Sharma JB, Gulati N. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 1992 December; 39(4): 291-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1361462&dopt=Abstract

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Preparing your patients to travel abroad safely. Part 3: Reducing the risk of malaria and dengue fever. Author(s): Thomas RE. Source: Can Fam Physician. 2000 May; 46: 1126-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10845139&dopt=Abstract

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Quantitation of T lymphocyte subsets helps to distinguish dengue hemorrhagic fever from classic dengue fever during the acute febrile stage. Author(s): Fadilah SA, Sahrir S, Raymond AA, Cheong SK, Aziz JA, Sivagengei K. Source: Southeast Asian J Trop Med Public Health. 1999 December; 30(4): 710-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10928365&dopt=Abstract

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Rapid detection of virus genome from imported dengue fever and dengue hemorrhagic fever patients by direct polymerase chain reaction. Author(s): Morita K, Maemoto T, Honda S, Onishi K, Murata M, Tanaka M, Igarashi A. Source: Journal of Medical Virology. 1994 September; 44(1): 54-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7798887&dopt=Abstract

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Rapid diagnosis and determination of duration of viraemia in dengue fever using a reverse transcriptase polymerase chain reaction. Author(s): Brown JL, Wilkinson R, Davidson RN, Wall R, Lloyd G, Howells J, Pasvol G. Source: Trans R Soc Trop Med Hyg. 1996 March-April; 90(2): 140-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8761573&dopt=Abstract

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Rapid diagnosis of primary dengue fever by the immunochromatographic test and by electron microscopy--a case report. Author(s): Allwinn R, Schieferstein C, Glauke S, Doerr HW. Source: Infection. 1999 November-December; 27(6): 365-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10624599&dopt=Abstract

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Reintroduction of dengue fever into the continental United States. I. Dengue surveillance in Texas, 1980. Author(s): Hafkin B, Kaplan JE, Reed C, Elliott LB, Fontaine R, Sather GE, Kappus K. Source: The American Journal of Tropical Medicine and Hygiene. 1982 November; 31(6): 1222-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7149106&dopt=Abstract

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Risk factors associated with an outbreak of dengue fever in a favela in Fortaleza, north-east Brazil. Author(s): Heukelbach J, de Oliveira FA, Kerr-Pontes LR, Feldmeier H. Source: Tropical Medicine & International Health : Tm & Ih. 2001 August; 6(8): 635-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11555429&dopt=Abstract

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Rubella cases mistaken for dengue fever. Author(s): Tan DS, Chew V, Nuruddin NM. Source: Singapore Med J. 1980 December; 21(6): 769-70. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7221591&dopt=Abstract

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Scientists try new strategy to eradicate dengue fever. Author(s): Kenyon G. Source: Bmj (Clinical Research Ed.). 1999 February 27; 318(7183): 555. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10037618&dopt=Abstract

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Sequential changes of serum transaminase and abdominal sonography in patients with suspected dengue fever. Author(s): Wang LY, Chang WY, Lu SN, Chen TP. Source: Gaoxiong Yi Xue Ke Xue Za Zhi. 1990 September; 6(9): 483-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2213970&dopt=Abstract

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Seroepidemiology and active surveillance of dengue fever/dengue haemorrhagic fever in Delhi. Author(s): Kurukumbi M, Wali JP, Broor S, Aggarwal P, Seth P, Handa R, Dhar L, Vajapayee M. Source: Indian Journal of Medical Sciences. 2001 March; 55(3): 149-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11482168&dopt=Abstract

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Serological & virological investigation of an outbreak of dengue fever in Gwalior, India. Author(s): Parida MM, Dash PK, Upadhyay C, Saxena P, Jana AM. Source: The Indian Journal of Medical Research. 2002 December; 116: 248-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807151&dopt=Abstract

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Serological evidence of dengue fever among refugees, Hargeysa, Somalia. Author(s): Botros BA, Watts DM, Soliman AK, Salib AW, Moussa MI, Mursal H, Douglas C, Farah M. Source: Journal of Medical Virology. 1989 October; 29(2): 79-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2600591&dopt=Abstract

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Serological evidence of dengue fever in the Bangladesh Republic. Author(s): Gaidamovich SY, Siddiqi SM, Haq F, Klisenko GA, Melnikova EE, Obukhova VR. Source: Acta Virol. 1980 March; 24(2): 153. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6107025&dopt=Abstract

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Spleen rupture in a patient with dengue fever. Author(s): Imbert P, Sordet D, Hovette P, Touze JE. Source: Trop Med Parasitol. 1993 December; 44(4): 327-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8134775&dopt=Abstract

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Status of antioxidants and other biochemical abnormalities in children with dengue fever. Author(s): Ray G, Kumar V, Kapoor AK, Dutta AK, Batra S. Source: Journal of Tropical Pediatrics. 1999 February; 45(1): 4-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10191585&dopt=Abstract

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Surveillance of dengue fever in French Guiana by monitoring the results of negative malaria diagnoses. Author(s): Talarmin A, Peneau C, Dussart P, Pfaff F, Courcier M, de Rocca-Serra B, Sarthou JL. Source: Epidemiology and Infection. 2000 August; 125(1): 189-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11057976&dopt=Abstract

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Symptoms of dengue fever in relation to host immunologic response and virus serotype, Puerto Rico, 1990-1991. Author(s): Cobra C, Rigau-Perez JG, Kuno G, Vorndam V. Source: American Journal of Epidemiology. 1995 December 1; 142(11): 1204-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7485067&dopt=Abstract

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The 1982 epidemic of dengue fever in Delhi. Author(s): Rao CV, Bagchi SK, Pinto BD, Ilkal MA, Bharadwaj M, Shaikh BH, Dhanda V, Dutta M, Pavri KM. Source: The Indian Journal of Medical Research. 1985 October; 82: 271-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4077169&dopt=Abstract

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The 1993 epidemic of dengue fever in Mangalore, Karnataka state, India. Author(s): Padbidri VS, Adhikari P, Thakare JP, Ilkal MA, Joshi GD, Pereira P, Guttikar SN, Walhekar BD, Chowta N, Hegde BM. Source: Southeast Asian J Trop Med Public Health. 1995 December; 26(4): 699-704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9139379&dopt=Abstract

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The absence of dengue virus in the skin lesions of dengue fever. Author(s): de Andino RM, Botet MV, Gubler DJ, Garcia C, Laboy E, Espada F, Waterman SH. Source: International Journal of Dermatology. 1985 January-February; 24(1): 48-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3997331&dopt=Abstract

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The basic reproduction number for dengue fever in Sao Paulo state, Brazil: 1990-1991 epidemic. Author(s): Marques CA, Forattini OP, Massad E. Source: Trans R Soc Trop Med Hyg. 1994 January-February; 88(1): 58-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8154004&dopt=Abstract

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The dengue fever epidemic in Delhi. Author(s): Goel A. Source: J Assoc Physicians India. 1999 June; 47(6): 653-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10999179&dopt=Abstract

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The dengue fever threat. Author(s): Glazebrook R. Source: Aust Nurses J. 1983 March; 12(8): 44-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6552175&dopt=Abstract

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The ethnoecology of dengue fever. Author(s): Whiteford LM. Source: Medical Anthropology Quarterly. 1997 June; 11(2): 202-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9186961&dopt=Abstract

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The features of imported dengue fever cases from 1996 to 1999. Author(s): Yamada KI, Takasaki T, Nawa M, Nakayama M, Arai YT, Yabe S, Kurane I. Source: Japanese Journal of Infectious Diseases. 1999 December; 52(6): 257-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10738370&dopt=Abstract

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The first patient with locally acquired dengue fever in Hong Kong. Author(s): Auyeung TW, Que TL, Lam KS, Ng HL, Szeto ML. Source: Hong Kong Medical Journal = Xianggang Yi Xue Za Zhi / Hong Kong Academy of Medicine. 2003 April; 9(2): 127-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668825&dopt=Abstract

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The Guillain-Barre syndrome following dengue fever. Author(s): Esack A, Teelucksingh S, Singh N. Source: The West Indian Medical Journal. 1999 March; 48(1): 36-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10375992&dopt=Abstract

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The pharmacokinetic responses of humans to 20 g of alanyl-glutamine dipeptide differ with the dosing protocol but not with gastric acidity or in patients with acute Dengue fever. Author(s): Klassen P, Mazariegos M, Solomons NW, Furst P. Source: The Journal of Nutrition. 2000 February; 130(2): 177-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10720166&dopt=Abstract

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The status of dengue fever virus in South Africa--serological studies and diagnosis of a case of dengue fever. Author(s): Blackburn NK, Meenehan G, Aldridge N. Source: Trans R Soc Trop Med Hyg. 1987; 81(4): 690-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2832982&dopt=Abstract

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The use of intravenous gammaglobulin in dengue fever, a case report. Author(s): Ascher DP, Laws HF, Hayes CG. Source: Southeast Asian J Trop Med Public Health. 1989 December; 20(4): 549-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2484144&dopt=Abstract

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Thyroid function in dengue fever, meningitis, encephalitis, poliomyelitis and other febrile conditions. Author(s): Parshad O, Melville GN, Prabhakar P. Source: The West Indian Medical Journal. 1986 June; 35(2): 126-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3739343&dopt=Abstract

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Unrecognized spotted fever group rickettsiosis masquerading as dengue fever in Mexico. Author(s): Zavala-Velazquez JE, Yu XJ, Walker DH. Source: The American Journal of Tropical Medicine and Hygiene. 1996 August; 55(2): 157-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8780453&dopt=Abstract

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Unusual neurologic manifestations occurring during dengue fever infection. Author(s): Patey O, Ollivaud L, Breuil J, Lafaix C. Source: The American Journal of Tropical Medicine and Hygiene. 1993 June; 48(6): 793802. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8333572&dopt=Abstract

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Upper gastrointestinal bleeding in dengue fever. Author(s): Tsai CJ, Kuo CH, Chen PC, Changcheng CS. Source: The American Journal of Gastroenterology. 1991 January; 86(1): 33-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1986551&dopt=Abstract

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Use of a computer model to identify potential hotspots for dengue fever in New Zealand. Author(s): de Wet N, Ye W, Hales S, Warrick R, Woodward A, Weinstein P. Source: N Z Med J. 2001 September 28; 114(1140): 420-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11700749&dopt=Abstract

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Vectors of dengue fever/dengue haemorrhagic fever with advances in their control. Author(s): Self LS. Source: Asian J Infect Dis. 1979 June; 3(2): 77-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=543815&dopt=Abstract

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Venezuela launches new campaign against dengue fever. Author(s): Johnson O. Source: Bmj (Clinical Research Ed.). 2002 September 7; 325(7363): 512. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12219753&dopt=Abstract

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Virologic and serologic surveillance for dengue fever in Jeddah, Saudi Arabia, 19941999. Author(s): Fakeeh M, Zaki AM. Source: The American Journal of Tropical Medicine and Hygiene. 2001 December; 65(6): 764-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11791972&dopt=Abstract

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You're the flight surgeon. Dengue fever. Author(s): Schmitz RA. Source: Aviation, Space, and Environmental Medicine. 1995 February; 66(2): 185-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7726789&dopt=Abstract

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CHAPTER 2. NUTRITION AND DENGUE FEVER Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and dengue fever.

Finding Nutrition Studies on Dengue Fever The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “dengue fever” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7

Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “dengue fever” (or a synonym): •

Acute management of dengue shock syndrome: a randomized double-blind comparison of 4 intravenous fluid regimens in the first hour. Author(s): Dong Nai Paediatric Hospital, Bien Hoa, Dong Nai Province, Vietnam. Source: Ngo, N T Cao, X T Kneen, R Wills, B Nguyen, V M Nguyen, T Q Chu, V T Nguyen, T T Simpson, J A Solomon, T White, N J Farrar, J Clin-Infect-Dis. 2001 January 15; 32(2): 204-13 1058-4838

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Corticosteroid-responsive prolonged thrombocytopenia following dengue haemorrhagic fever. Author(s): Department of Medicine, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur. Source: Leong, K W Srinivas, P Med-J-Malaysia. 1993 September; 48(3): 369-72 0300-5283

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Determination of tumor necrosis factor-alpha levels in dengue virus infected patients by sensitive biotin-streptavidin enzyme-linked immunosorbent assay. Author(s): Department of Microbiology, Faculty of Public Health, Mahidol University, Bangkok, Thailand. [email protected] Source: Kittigul, L Temprom, W Sujirarat, D Kittigul, C J-Virol-Methods. 2000 October; 90(1): 51-7 0166-0934

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Fluid replacement in dengue shock syndrome: a randomized, double-blind comparison of four intravenous-fluid regimens. Author(s): The Centre for Tropical Diseases and the Wellcome Trust Clinical Research Unit, Ho Chi Minh City, Vietnam. Source: Dung, N M Day, N P Tam, D T Loan, H T Chau, H T Minh, L N Diet, T V Bethell, D B Kneen, R Hien, T T White, N J Farrar, J J Clin-Infect-Dis. 1999 October; 29(4): 787-94 1058-4838

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Impact of dengue virus infection and its control. Author(s): Department of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki City, Japan. Source: Igarashi, A FEMS-Immunol-Med-Microbiol. 1997 August; 18(4): 291-300 09288244

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Impaired T cell proliferation in acute dengue infection. Author(s): Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical Center, Worcester 01655, USA. Source: Mathew, A Kurane, I Green, S Vaughn, D W Kalayanarooj, S Suntayakorn, S Ennis, F A Rothman, A L J-Immunol. 1999 May 1; 162(9): 5609-15 0022-1767

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Protection against marked plasma leakage in dengue haemorrhagic fever by infusion of carbazochrome sodium sulfonate (AC-17). Author(s): Department of Physiology, Kobe University School of Medicine, Japan. Source: Funahara, Y Sumarmo Shirahata, A Harun, S R Setiabudy Dharma, R Nathin, M A Karjomanggolo, T W Tamaela, L A Southeast-Asian-J-Trop-Med-Public-Health. 1987 September; 18(3): 356-61 0038-3619

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Susceptibility to dengue hemorrhagic fever in vietnam: evidence of an association with variation in the vitamin d receptor and Fc gamma receptor IIa genes. Author(s): Wellcome Trust Centre for Human Genetics, University of Oxford, United Kingdom. Source: Loke, H Bethell, D Phuong, C X Day, N White, N Farrar, J Hill, A Am-J-TropMed-Hyg. 2002 July; 67(1): 102-6 0002-9637

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The differentiation state of monocytic cells affects their susceptibility to infection and the effects of infection by dengue virus. Author(s): Department of Microbiology, Moyne Institute, Trinity College, University of Dublin, Ireland. Source: O'Sullivan, M A Killen, H M J-Gen-Virol. 1994 September; 75 ( Pt 9)2387-92 00221317

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The pharmacokinetic responses of humans to 20 g of alanyl-glutamine dipeptide differ with the dosing protocol but not with gastric acidity or in patients with acute Dengue fever. Author(s): Institute for Biological Chemistry and Nutrition, University of Hohenheim, Stuttgart, Germany. Source: Klassen, P Mazariegos, M Solomons, N W Furst, P J-Nutr. 2000 February; 130(2): 177-82 0022-3166

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The role of prostacyclin (PGI2) and thromboxane A2 (TXA2) in pathogenesis of dengue hemorrhagic fever (DHF). Author(s): Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. Source: Preeyasombat, C Treepongkaruna, S Sriphrapradang, A Choubtum, L J-MedAssoc-Thai. 1999 November; 82 Suppl 1S16-21 0125-2208

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Transient CD4/CD8 ratio inversion and aberrant immune activation during dengue virus infection. Author(s): Department of Pediatrics, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China. Source: Liu, C C Huang, K J Lin, Y S Yeh, T M Liu, H S Lei, H Y J-Med-Virol. 2002 October; 68(2): 241-52 0146-6615

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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CHAPTER 3. ALTERNATIVE MEDICINE AND DENGUE FEVER Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to dengue fever. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to dengue fever and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “dengue fever” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to dengue fever: •

Australia's contribution to tropical health: past and present. Author(s): Doherty R. Source: The Medical Journal of Australia. 1993 April 19; 158(8): 552-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8487721&dopt=Abstract

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Critical regions, a profile of Honduras. Author(s): Almendares J, Sierra M, Anderson PK, Epstein PR. Source: Lancet. 1993 December 4; 342(8884): 1400-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7901687&dopt=Abstract

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Field evaluation of a smoke-generating formulation containing beta-cypermethrin against the dengue vector in Argentina. Author(s): Masuh H, De Licastro SA, Lopez PA, Vega C, Zerba E.

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Source: J Am Mosq Control Assoc. 2003 March; 19(1): 53-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12674535&dopt=Abstract •

Field evaluation of cypermethrin and cyfluthrin against dengue vectors in a housing estate in Malaysia. Author(s): Sulaiman S, Pawanchee ZA, Othman HF, Shaari N, Yahaya S, Wahab A, Ismail S. Source: J Vector Ecol. 2002 December; 27(2): 230-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546459&dopt=Abstract

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Hazards of misdiagnosis due to Vietnamese folk medicine. Author(s): Golden SM, Duster MC. Source: Clinical Pediatrics. 1977 October; 16(10): 949-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=891073&dopt=Abstract

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Impact of dengue virus infection and its control. Author(s): Igarashi A. Source: Fems Immunology and Medical Microbiology. 1997 August; 18(4): 291-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9348165&dopt=Abstract

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Medicine in tropical Australia. Author(s): Currie B. Source: The Medical Journal of Australia. 1993 May 3; 158(9): 609, 612-5. Erratum In: Med J Aust 1993 June 21; 158(12): 868. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8479379&dopt=Abstract

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Nematocera (Ceratopogonidae, Psychodidae, Simuliidae and Culicidae) and control methods. Author(s): Braverman Y. Source: Rev Sci Tech. 1994 December; 13(4): 1175-99. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7711309&dopt=Abstract

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The use of commercial saponin from Quillaja saponaria bark as a natural larvicidal agent against Aedes aegypti and Culex pipiens. Author(s): Pelah D, Abramovich Z, Markus A, Wiesman Z. Source: Journal of Ethnopharmacology. 2002 August; 81(3): 407-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127245&dopt=Abstract

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Treatment seeking behavior of DHF patients in Thailand. Author(s): Okanurak K, Sornmani S, Mas-ngammueng R, Sitaputra P, Krachangsang S, Limsomboon J.

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Source: Southeast Asian J Trop Med Public Health. 1997 June; 28(2): 351-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9444020&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMDHealth: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to dengue fever; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Herbs and Supplements Guatteria Alternative names: Guatteria gaumeri Greenman Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON DENGUE FEVER Overview In this chapter, we will give you a bibliography on recent dissertations relating to dengue fever. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “dengue fever” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on dengue fever, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Dengue Fever ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to dengue fever. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Folk Models and Household Ecology of Dengue Fever in an Urban Community of the Dominican Republic (mexico) by Salazar, Diego Rojas, Phd from University of South Florida, 1993, 229 pages http://wwwlib.umi.com/dissertations/fullcit/9323699

•

The Evolution of Dengue Virus Type 3 in Association with the Emergence of Dengue Hemorrhagic Fever in Sri Lanka by Messer, William Brogdon; Phd from The University of North Carolina at Chapel Hill, 2003, 238 pages http://wwwlib.umi.com/dissertations/fullcit/3086580

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Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. PATENTS ON DENGUE FEVER Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “dengue fever” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on dengue fever, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Dengue Fever By performing a patent search focusing on dengue fever, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 8Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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example of the type of information that you can expect to obtain from a patent search on dengue fever: •

Attenuated dengue-2 virus vaccine Inventor(s): Dubois; Doria R. (Wheaton, MD), Eckels; Kenneth H. (Rockville, MD), Henchai; Erik A. (Rockville, MD), Hoke; Charles H. (Columbia, MD), Innis; Bruce L. (Haverford, PA), Kanesa-thasan; Niranian (Rockville, MD), Putnak; Joseph R. (Silver Spring, MD), Vaughn; David (Silver Spring, MD) Assignee(s): The United States of America as represented by the Secretary of the Army (Washington, DC) Patent Number: 6,511,667 Date filed: March 24, 2000 Abstract: The present invention provides vaccine compositions of attenuated dengue-2 virus. More specifically, the attenuated virus is produced by serial passage in PDK cells. The invention also provides methods for stimulating the immune system of an individual to induce protection against dengue-2 virus by administration of attenuated dengue-2 virus. Excerpt(s): Dengue fever is caused by any of four serotypes of dengue virus, dengue-1, dengue-2, dengue-3, and dengue-4, which are transmitted to humans by mosquitoes. In adults, dengue infections typically cause self-limited but incapacitating acute illness with fever, muscle pains, headache and an occasional rash. The illness may be complicated by hemorrhagic fever, which may be manifested by a positive tourniquet test, spontaneous petechiae, frank bleeding, and/or shock. Dengue hemorrhagic fever is fatal in about 0.5% of cases. Patients who have antibody from an earlier dengue infection who are subsequently infected by another dengue strain have been shown to be at higher risk for dengue hemorrhagic fever. The mosquito vectors of dengue viruses are found in all tropical and sub-tropical areas of the world and in some temperate areas of the United States, Europe, Africa, and the Middle East. In recent years, endemic and epidemic dengue infections have occured in Central and South Ameria, Southeast Asia, India, Africa, the Caribbean and Pacific regions. Vector control is impractical. Development of live attenuated virus vaccines for dengue has been pursued by the Walter Reed Army Institute of Research (WRAIR) and Mahidol University in Thailand (Kanesa-thasan 1997), (Bhamarapravati 1997). Early efforts established that there were no known, reliable genetic or phenotypic markers or proven animal models for predicting attenuation of dengue virus. Hence, the principal means of determining the safety and immunogenicity of a candidate vaccine was to evaluate it in volunteers. Over the past forty years, many dengue vaccine strains were found to be unsuitable for humans because of over-attenuation, which rendered them insufficiently immunogenic, or because they were under-attenuated, resulting in dengue fever. Many months or years of testing were needed before a candidate vaccine could be determined to be acceptable. Web site: http://www.delphion.com/details?pn=US06511667__

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Attenuated dengue-3 virus vaccine Inventor(s): Dubois; Doria R. (Wheaton, MD), Eckels; Kenneth H. (Rockville, MD), Hoke; Charles H. (Columbia, MD), Innis; Bruce L. (Hayerford, PA), Putnak; Joseph R. (Silver Spring, MD), Vaughn; David (Silver Spring, MD) Assignee(s): The United States of America as represented by the Secretary of the Army (Washington, DC) Patent Number: 6,528,065 Date filed: March 24, 2000 Abstract: The present invention provides immunogenic compositions of attenuated dengue-1 virus. More specifically, the attenuated virus is produced by serial passage in PDK cells. The invention also provides methods for stimulating the immune system of an individual to induce protection against dengue-1 virus by administration of attenuated dengue-1 virus. Excerpt(s): Dengue fever is caused by any of four serotypes of dengue virus, dengue-1, dengue-2, dengue-3, and dengue-4, which are transmitted to humans by mosquitoes. In adults, dengue infections typically cause self-limited but incapacitating acute illness with fever, muscle pains, headache and an occasional rash. The illness may be complicated by hemorrhagic fever, which may be manifested by a positive tourniquet test, spontaneous petechiae, frank bleeding, and/or shock. Dengue hemorrhagic fever is fatal in about 0.5% of cases. Patients who have antibody from an earlier dengue infection who are subsequently infected by another dengue strain have been shown to be at higher risk for dengue hemorrhagic fever. The mosquito vectors of dengue viruses are found in all tropical and sub-tropical areas of the world and in some temperate areas of the United States, Europe, Africa, and the Middle East. In recent years, endemic and epidemic dengue infections have occured in Central and South Ameria, Southeast Asia, India, Africa, the Caribbean and Pacific regions. Vector control is impractical. A concerted investigation was undertaken at the WRAIR to select four attenuated dengue vaccine candidates, one for each serotype. As with other successful human vaccines, it was planned that passaged virus would be tested at the highest and lowest passage levels available. One or another of these extremes might be found suitable. If necessary, further intermediate pasage levels could be developed for testing. In this approach, there was no intent to predict which, if any biological markers will correlate with virulence of virus in human beings. The identification of a successful human vaccine for one DEN type might validate biological markers of attenuation and permit improved selection of other attenuated viruses. The empiric approach to separate evaluation of multiple passage levels is based upon the precedent of modern attenuated virus vaccines; for example rubella strains that differed by only a few duck embryo passages varied markedly in human virulence (Halstead et al., 1970, JAMA 211, 911-916). Web site: http://www.delphion.com/details?pn=US06528065__

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cDNA sequence of Dengue virus serotype 1 (Singapore strain) Inventor(s): Chan; Yow-Cheong (Singapore, SG), Fu; Jianlin (Singapore, SG), Tan; BoonHuan (Singapore, SG), Tan; Yin-Hwee (Singapore, SG), Yap; Eu-Hian (Singapore, SG) Assignee(s): Insititute of Molecular and Cell Biology (SG) Patent Number: 6,017,535 Date filed: December 16, 1994

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Abstract: DENI-S275/90 (ECACC V92042111) is a new strain of Dengue virus serotype 1. The complete cDNA sequence of this virus has been cloned and protein-coding fragments thereof have been used in the construction of expression plasmids. DEN1S275/90 in inactivated form, DEN1-S275/90 polypeptides or fusion proteins thereof can be incorporated into vaccines for immunisation against DEN1-S275/90 and other DEN1 viruses. The invention further provides diagnostic reagents e.g. labelled antibodies to DEN1-S275/90 proteins, and kits to detect DEN1 virus. Excerpt(s): The present invention relates to Dengue Virus Type 1. Dengue virus infection may lead to dengue fever (DF) or its more severe dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). DHF is an important virus disease of global significance, especially in Southeast Asia. There are four serotypes of Dengue virus (DEN1, DEN2, DEN3 and DEN4) belonging to the family Flaviviradae. The complete genomic sequence of DEN2 (Jamaica) has been published by Deubel et al; Virology 165, 234-244 (1988). The complete genomic sequence of DEN3 (HS87) has been published by Osatomi and Sumiyoshi; Virology 176, 643-647 (1990). The complete genomic sequence of DEN4 has been published by Zhao et al; Virology 155, 77-88. To date, only a partial sequence of any variant of DEN1, DEN1 (Nauru Island), has been determined; Mason et al, Virology 161, 262-267 (1987). We have now identified a previously unknown strain of DEN1 and established its complete nucleotide sequence. The new strain, DEN1-S275/90, was deposited at the European Collection of Animal Cell Cultures (ECACC) Porton Down, GB under Budapest Treaty conditions on (Apr. 21, 1992) and given accession number V92042111. DEN1-S275/90 differs significantly from DEN2, DEN3 and DEN4 in terms of sequence homology. There are also a number of significant differences between DEN1-S275/90 and DEN1 (Nauru Island). Web site: http://www.delphion.com/details?pn=US06017535__ •

Dengue nucleic acid vaccines that induce neutralizing antibodies Inventor(s): Hayes; Curtis G. (Frederick, MD), Hoffman; Stephen L. (Gaithersburg, MD), Kochel; Tadeusz J. (Frederick, MD), Porter; Kevin R. (Gaithersburg, MD), Raviprakash; Kanakatte (Silver Spring, MD) Assignee(s): The United States of America as represented by the Secretary of the Navy (Washington, DC) Patent Number: 6,455,509 Date filed: June 4, 1997 Abstract: A vaccine for promoting an immune response in a mammalian subject includes a eucaryotic plasmid expression vector which include at least part of the envelope gene and optionally, the PreM gene of dengue virus. In order to minimize immune enhancement, vaccines of up to the four serotypes of dengue are combined in a single vaccine. The vaccine in a suitable pharmaceutical carrier constitutes a pharmaceutical composition which is injected into the subject. Excerpt(s): This invention relates to nucleic acid vaccines and more specifically to Dengue nucleic acid vaccines. Dengue (Den) viruses belong to the flavivirus genus of the family Flaviviridae and are of four serotypes, Den 1-4. Dengue viruses are positive strand RNA viruses which code for ten genes. The genes are translated as a polyprotein which is cleaved by host and viral proteinases. The virus envelope (E) protein is the major antigen against which neutralizing antibodies are directed. These antibodies have been shown to be capable of protecting against dengue virus infection.sup.1. The

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membrane protein also appears on the virion surface and is required for the proper processing of E. Dengue viruses are transmitted primarily by the mosquito, Aedes aegypti, and are a major cause of morbidity and mortality throughout tropical and subtropical regions worldwide.sup.2. It is estimated that there are over 100 million cases, annually, of dengue fever.sup.3. Human dengue illnesses range from an acute undifferentiated fever to dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). A primary infection usually causes dengue fever. The illness is generally mild and the person apparently acquires a life long immunity against the serotype of dengue virus causing the infection. However, if a person acquires a second dengue infection with a different serotype, the illness may be more severe and lead to hemorrhagic fever or shock syndrome, with a mortality rate between one and five percent. The increased severity of the secondary infection is caused by an immune enhancement phenomenon.sup.4. Immune enhancement begins when non-neutralizing antibodies, generated from the earlier infection with one dengue serotype, bind to but do not neutralize the virus causing the secondary infection. The Fc portion of the antibody in the virus-antibody complexes then binds to the Fc receptors present on mononuclear phagocytes of the immune system, resulting in enhanced infection of these cells. The enhanced infection leads to the release of cytokines that ultimately cause capillary leak and coagulopathy, the principal pathogenic mechanisms in DHF/DSS. Web site: http://www.delphion.com/details?pn=US06455509__ •

Dengue virus peptides and methods Inventor(s): Chan; Lily (Singapore, SG), Guan; Ming (Singapore, SG) Assignee(s): Genelabs Diagnostics PTE. Ltd. (SG) Patent Number: 5,824,506 Date filed: August 15, 1994 Abstract: Peptide antigens derived from the dengue virus type-2 glycoprotein NS1 are provided. The peptide antigens are specifically immunoreactive with sera from individuals infected with the dengue virus. The antigens are useful as diagnostic tools in determining whether an individual has been or is infected with dengue virus, and for discriminating between infection with dengue virus and infection with related flaviviruses. The antigens are also useful in vaccine compositions for immunizing individuals against infection with the dengue virus. Excerpt(s): This invention relates to epitopes of the dengue virus useful in diagnostic methods, assays and vaccines for dengue virus infection in humans. Aaskov, J. G. et al., Arch. Virol. 105:209 (1989). Bauminger, S. et al., Methods Enzymol. 70:151 (1980). Web site: http://www.delphion.com/details?pn=US05824506__

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Injection viral treatment Inventor(s): Fabunan; Ruben G. (329 N. Vendome St., Los Angeles, CA 90026) Assignee(s): none reported Patent Number: 6,172,053 Date filed: September 13, 1999 Abstract: The present invention relates to a therapeutic composition and formulation for the treatment of viral diseases such as, Dengue fever and influenza. More particularly,

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to therapeutic preparation comprising substantially water soluble, local anesthetic of the ester type, procaine hydrochloride and a water soluble glucocorticoid, dexamethasone sodium phosphate. Excerpt(s): The present invention relates to a therapeutic composition for the treatment of viral infections and a method of administration thereof. More particularly, the invention relates to a therapeutic composition including a substantially water soluble local anesthetic of the ester type injectable and a water soluble glucocorticoid injectable, and to the method of administering said composition to an infected patient. In both Third-world and developing countries and also in developed countries, there is a prevalent need for an economical yet effective viral treatment to both ease human suffering and save lives. The present invention relates directly to both of these needs since it has been compassionately used to treat and/or cure a number of known pathogenic viruses, including but not limited to human immunodeficiency virus (HIV) causing acquired immunodeficiency syndrome (AIDS), Dengue fever virus, influenza virus, rhinovirus causing common colds, herpes zoster virus, mumps virus, measles virus, hepatitis virus, conjunctivitis virus, rabies virus, chickenpox virus and other viruses found in equatorial environments common to Third-World and developing countries but also found with increasing prevalence in industrialized nations. To the best of the inventor's knowledge, in medical textbooks or in current clinical practice, there is no treatment, cure or vaccine for the Dengue fever virus. This invention comes about after many years of field testing, and now over two years of clinical studies at the Fabunan Medical Clinic located in the province of Zambales, the Philippines in Southeast Asia. Each known virus that has been treated with this composition has shown a remarkably significant improvement and/or curative result with no serious side effects. Routine cases were clinically diagnosed and then treatment began. A patient usually improved and recovered within seventy two hours but, sometimes, more time was needed. Web site: http://www.delphion.com/details?pn=US06172053__ •

Isothermal transcription based assay for the detection and genotyping of dengue virus Inventor(s): Hurteau; Gregory J. (Alexandria, VA), Lee; Eun Mi (Gaithersburg, MD), Romano; Joseph W. (Derwood, MD) Assignee(s): Akzo Nobel, N.V. (Arnhem, NL) Patent Number: 5,968,732 Date filed: December 31, 1997 Abstract: An isothermal transcription based amplification assay for dengue virus RNA uses primer combinations for sequences within the envelope gene or the 3' non-coding region of the virus and a probe. Probes may be specific for a serotype of dengue virus. Excerpt(s): The present invention is directed to an isothermal transcription based assay for the detection and genotyping of dengue virus. The present invention is also directed to oligonucleotides for amplifying dengue RNA and for type-specific probes used in the detection of the amplification product. Dengue virus infection is an arthropod-borne viral disease which has very high morbidity and mortality in humans. Dengue is a member of Flaviviridae, and utilizes an 11 kb single stranded, positive RNA genome. The genome encodes 3 proteins and contains additional non-coding regions at the 5' and 3' ends. There are currently four different dengue virus subtypes known, which are

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distributed among geographically distinct tropical and subtropical regions. All four subtypes can cause an array of maladies, ranging from an acute, self limited illness (dengue fever, DF) to the more severe and potentially fatal dengue hemorrhagic fever or dengue shock syndrome (dengue hemorrhagic fever, DHF). As many as 50 million human cases occur annually, with an estimated 10,000 infant deaths due to the hemorrhagic form of dengue. Immunity to one serotype does not protect against infection by the others. In fact, sequential infection by another serotype substantially increases the probability of developing DHF (Rico-Hesse et al, Virology 230, 244-251 (1997)). For this reason it may be critical to be able to determine the genotype of the dengue virus for management of the disease. Web site: http://www.delphion.com/details?pn=US05968732__ •

Method and kit for detection of dengue virus Inventor(s): Cassidy; Kevin (Toronto, CA), Dubois; Doria R. (Wheaton, MD), Eckels; Kenneth (Rockville, MD), Putnak; J. Robert (Silver Spring, MD) Assignee(s): The United States of America as represented by the Secretary of the Army (Washington, DC) Patent Number: 6,190,859 Date filed: April 17, 1995 Abstract: An inactivated dengue virus vaccine to immunize and protect humans against dengue fever is described. The vaccine is based on dengue viruses which have been propagated to high titers in suitable cells, purified and inactivated under conditions which destroy infectivity but preserve immunogenicity, a high level of which is demonstrated in animal models. Uses of the inactivated dengue virus for detecting antibodies to dengue and kits therefor are also described. Excerpt(s): Dengue is an acute viral disease of man which is transmitted by mosquitos. It is endemic in the tropics and subtropics, worldwide, where an estimated 100,000,000 cases occur annually (Reviewed in Henchal and Putnak, Clin. Microbiol. Revs 3: 376-96, 1990. The entire content of all documents cited herein are hereby incorporated by reference). Dengue is characterized clinically by biphasic fever, rash and hematopoietic depression, and by constitutional symptoms such as malaise, arthralgia, myalgia and headache (Reviewed in Monath, Flaviviruses. In: Fields, B. N. et al. Fields Virology, 2nd ed. Vol 1, New York: Raven Press, 1990, p. 763-814). Infrequently, more severe disease is seen, manifested by hemorrhage which may progress to lethal shock (Halstead, S. B. Yale J. Biol. Med. 37: 434-54, 1965). The timing of these manifestations, somewhat after the early febrile period, and their frequent association with secondary dengue infection and pre-existing antibody has led to the hypothesis that they are immunologically mediated (Halstead, S. B. Yale J. Biol. Med. 42: 350-62, 1970; Sankawibha et al. Am. J. Epidemiol. 120: 653-69, 1984). Although relatively rare, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) may be significant causes of death in children. At present, there is no vaccine to protect against dengue and attempts to prevent disease by controlling the mosquito vector have proven largely ineffective. Dengue viruses are members of the family flaviviradae which includes over sixty members (Westaway, E. G. et al. Intervirology 24:183-92, 1985). Within the dengue group are four serotypes, dengue-type-one (dengue-1), dengue-2, dengue-3, and dengue-4, among which there is considerable genetic and antigenic similarity but no significant cross-neutralization (Calisher C. H. et al. J. Gen. Virol. 70: 37-43, 1989). Like the family prototype, yellow fever (YF) virus, they are enveloped, single-stranded RNA

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viruses approximately 50 nm in size (Reviewed in Henchal and Putnak, 1990, supra). Their 10.5 kilobase (kb) genome encodes ten proteins, three virion structural proteins at the 5' end of the RNA beginning with capsid (C), matrix (M), its precursor pre-matrix (prM) and envelope (E), followed by seven nonstructural (NS) proteins, NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5 (Chambers, T. J. et al. Annu. Rev. Microbiol. 44: 64988, 1989). Virus neutralizing antibody, thought to play a primary role in immunity, is directed against the E protein (Qureshi, A. A. and Trent, D. W. Infect. Immun. 8: 993-9, 1973; Gentry, M. K. et al. Am. J. Trop. Med. Hyg. 31: 548-55, 1982), however, antibodies and T-cells directed against epitopes of other structural and even nonstructural proteins may also be important in subserving immunity to virus infection (Schlesinger, J. J. et al., J. Gen. Virol. 68:853-57, 1987). Currently, only two flavivirus vaccines have been licensed by the United States Food and Drug Administration (FDA) for human use, liveattenuated yellow fever virus (17D strain) developed by Theiler and coworkers in the 1930s (Theiler, M. and Smith, H. H. J. Exp. Med. 65: 748-800, 1937), and purified, formalin-inactivated Japanese encephalitis (JE) virus developed in the 1960s in Japan (Takaku , K. et al., Biken J. 11:25-39, 1968). Both have proven to be safe and effective, eliciting high titers of virus-neutralizing antibody and conferring solid protection (Hoke, C. H. et al. N. Engl. J. Med. 319: 608-13, 1988; Reviewed in Monath, 1990, supra). Also of note is a purified, formalin-inactivated vaccine for tick-borne encephalitis virus developed in the 1970s in Austria (Kunz, C. et al. J. Med. Virol. 6: 103-9, 1980) which is used successfully in many European countries. Web site: http://www.delphion.com/details?pn=US06190859__ •

Methods and reagents for rapid diagnosis of dengue virus infection Inventor(s): Ennis; Francis A. (Shrewsbury, MA), Ishiko; Hiroaki (Fujimi, JP), Sudiro; T. Mirawati (Jakarta, ID) Assignee(s): University of Massachusetts (Worcester, MA) Patent Number: 5,939,254 Date filed: April 28, 1997 Abstract: Specific primers that amplify a portion of the 3'-noncoding regions of dengue virus types 1, 2, 3 and 4, and a method of using these primers in a rapid reverse transcriptase-polymerase chain reaction (RT-PCR) for specific detection of dengue viruses, but not other flaviviruses, is disclosed. Excerpt(s): The invention relates to methods and reagents for detecting dengue viruses. Dengue virus infections are serious health problems in many areas of the world. Dengue virus can cause two forms of disease, dengue fever (DF) and dengue hemorrhagic fever (DHF). While DF is a self-limiting febrile disease, DHF can lead to life-threatening complications. Laboratory diagnosis of dengue virus infection has depended mainly upon the isolation of dengue virus using mosquito cell cultures or inoculation of mosquitos, detection of anti-dengue antibody by IgM or IgG ELISA, and/or hemagglutination inhibition (HI) assays. Isolation of dengue virus is tedious and time consuming, however, and serological testing generally requires paired serum samples obtained several days or weeks apart, which are not always available. Polymerase chain reaction (PCR) has the potential for sensitive, specific, and rapid detection of minute quantities of certain genetic material in clinical specimens, thus providing an attractive approach for the rapid diagnosis of dengue virus infection. Several methods of reverse transcriptase (RT)-PCR using different pairs of primers for dengue viruses and different approaches for the detection of amplification products

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have been previously reported. However, most of the published methods require more than 24 hours for analysis. Rapid RT-PCR methods for detection of dengue viremia have been reported, but they have not been shown to detect all four dengue serotypes in clinical specimens. The objective of several of these reports was to determine the serotype of dengue virus strain with which an individual was infected. RT-PCR followed by hybridization to serotype-specific probes, or RT-PCR followed by nested PCR, have been used for this purpose. Lanciotti et al., J. Clin. Microbiol., 30:545-551 (1992). Although these methods are sensitive, they still require considerable time and labor for use in patient management. Morita et al. describes a rapid and simple method using NP-40 and serotype-specific primers, in which RNA isolation, virus detection and typing can be done in a single reaction tube. Morita et al., J. Clin. Microbiol., 29:21072110 (1991); J. Med. Virol., 44:54-58 (1994). Web site: http://www.delphion.com/details?pn=US05939254__ •

Pre-M/M epitopes of dengue virus, synthetic peptides, chimeric proteins and their use Inventor(s): Acosta; Osvaldo Reyes (Habana, CU), Antunez; Maritza Pupo (Habana, CU), De La Cotera; Jose Luis Pelegrino Martinez (Habana, CU), Diaz; Ana Beatriz Perez (Habana, CU), Diaz; Luis Morier (Habana, CU), Insuita; Omaida Perez (Habana, CU), Lazo; Orlando Luis Pardo (Habana, CU), Nieto; Gerardo Enrique Guillen (Habana, CU), Palomares; Gabriel Padron (Habana, CU), Perez; Hilda Elisa Garay (Habana, CU), Ramudo; Susana Vazquez (Habana, CU), Roche; Rosmari Rodriguez (Habana, CU), Santiago; Glay Chinea (Habana, CU), Tirado; Guadalupe Guzman (Habana, CU), Vera; Maylin Alvarez (Habana, CU) Assignee(s): Centro de Ingeniera Genetic Y Biotechnologies (CIGB) (Habana, CU), Instituto de Medicina Tropical "Pedro Kouri" (Habana, CU) Patent Number: 6,383,488 Date filed: October 14, 1999 Abstract: The present invention relates to five synthetic peptides of pre-M/M protein of Dengue-2 virus, corresponding to amino acid sequences 3-31, 45-67, 57-92, 69-93 and 103-124. The anti-peptide immune response was evaluated in mice. Recombinant fusion proteins were also obtained, including regions of pre-M/M protein. The presence of B cell epitopes in both mice and humans was demonstrated in the pre-M/M protein peptides. Peptides 3-31 and 103-124 elicited neutralizing antibodies against the four serotypes of Dengue virus. Virus-specific proliferative responses were demonstrated in mice immunized with non-conjugated peptides 3-31 and 57-92. Mice immunized with conjugated peptides 3-31, 57-92, and 69-93 were protected when they were challenged with Dengue-2 virus. Thus, the presence of sequential epitopes in Pre-M/M protein of Dengue-2 virus was demonstrated, as well as their relevance in the immune response against this flavivirus. Excerpt(s): The present invention is in the field of biotechnology and relates to recombinant DNA techniques, in particular to the production of synthetic peptides coding for pre-M/M protein of Dengue virus serotype 2 and chimeric proteins which contain epitopes of pre-M/M protein of Dengue virus serotype 2 and 4. The technical objective is to identify Pre-M/M neutralizing and protective epitopes, cross reactive for all dengue virus serotypes to obtain an immunogen for human vaccination. Dengue virus belongs to the Flavivirus genus, family Flaviviridae (Westaway, E. G. et al. 1985. Flaviviridae. Intervirol. 24 p.183). It is an enveloped virus with a single RNA chain of

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positive polarity as genetic material, which codes for a polyprotein processed co- and post-transductionally by cellular and viral proteases. Web site: http://www.delphion.com/details?pn=US06383488__ •

Recombinant dengue virus DNA fragment Inventor(s): Kelly; Eileen P. (Takoma Park, MD), King; Alan D. (Washington, DC) Assignee(s): The United States of America as represented by the Secretary of the Army (Washington, DC) Patent Number: 6,074,865 Date filed: July 20, 1995 Abstract: A recombinant protein encompassing the complete envelope glycoprotein and a portion of the carboxy-terminus of the membrane/premembrane protein of dengue 2 virus was expressed in baculovirus as a protein particle. The recombinant protein particle was purified and found to provide protection against lethal challenge with dengue 2 virus in mice. Excerpt(s): This invention relates to the production and purification of a recombinant protein for use as a diagnostic tool and as a vaccine against Dengue virus. Dengue (DEN) viruses are human pathogens with a significant threat to world health. These viruses are estimated to cause several hundred thousand cases of dengue fever, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) annually (Shope, R. E. In: The Togaviruses. Schlesinger, R. W. (Ed.) Academic Press, New York. 1980, pp. 47-82; Monath, T. P. In: The Togaviridae and Flaviviridae, Schlesinger, S. and Schlesinger, M. J. (Eds.) New York and London, 1986, pp. 375-440; Halstead, S. B. Bull. W.H.O. 1980, 58, 121; Halstead, S. B. Am. J. Epidemiol. 1984, 114, 632-648) The complete content of all documents cited herein are hereby incorporated by reference. Dengue viruses are members of the family Flaviridae and are transmitted by Aedes mosquitoes (Halstead, S. B. Science 1988, 239, 476-481). There are four serological types, DEN-1, DEN-2, DEN-3 and DEN-4, distinguishable by complement-fixation assays (Sabin, A. B. and Young, I. A. Proc. Soci. Exp. Biol. Med. 1949, 69, 291-296), virus plaque-reduction neutralization tests (Russell, P. K. and Nisalak, A. J. Immunol. 1967, 99, 291-296) and immunoassays using monoclonal antibodies (MAbs) (Gentry, M. K. et al. Am. J. Trop. Med. Hyg. 1982, 31, 548-555; Henchal, E. A. et al. Am. J. Trop. Med. Hyg. 1982, 31, 830-836). Dengue viruses are composed of a single-stranded RNA molecule of positive polarity (messenger sense) which is contained within a nucleocapsid composed of capsid (C) protein. The capsid is surrounded by a lipid envelope about 50 nm in diameter in which are embedded the envelope (E) glycoprotein and the matrix (M) protein. Both the structural and nonstructural (NS) proteins are encoded by a single, long open reading frame of about 10.5 kilobases arranged as follows: C-PreM/M-E-NS1-NS2A-NS2B-NS3NS4A-NS5 (Rice, C. M. et al. Science 1985, 229, 726-733; Wengler, G. et al. Virology 1985, 147, 264-274; Castle, E. et al. Virology 1986, 149, 10-26; Zhao, B. et al. Virology 1986, 155, 77-88; Mason, P. W. et al. Virology 1987, 161, 262-267; Mackow, E. et al. Virology 1987, 159, 217-228; Sumiyoshi, H. et al. Virology 1987, 161, 497-510; Irie, K. et al. Gene 1989, 74, 197-211). Web site: http://www.delphion.com/details?pn=US06074865__

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Recombinant dengue virus envelope protein/maltose-binding protein antigens and subunit vaccine compositions containing said antigens Inventor(s): Hayes; Curtis G. (Frederick, MD), Porter; Kevin R. (Gaithersburg, MD), Simmons; Monika (Gaithersburg, MD) Assignee(s): The United States of America as represented by the Secretary of the Navy (Washington, DC) Patent Number: 5,895,651 Date filed: June 27, 1996 Abstract: A recombinant fusion protein (DEN-2 MBP) containing the B domain of the due (DEN 2 envelope protein is disclosed as a candidate subunit immunogen for vaccination against dengue virus infection. A gene fragment encoding amino acid 298 to amino acid 400 of the DEN-2 virus envelope was expressed as a fusion protein with the maltose binding protein (MBP) of Escherichia coli (E. coli). The recombinant fusion protein was purified and analyzed for its antigenicity imunogenicity and ability to protect mice against lethal challenge. This antigen is detected by monoclonal antibody (3H5) which is specific for a neutralizing epitope on the DEN-2 envelope and reacted with homologous polyclonal mouse immune ascitic fluid and DEN-2 immune human sera. A recombinant fusion plasmid bearing the DEN-2 MBP DNA sequence, expressing the fusion product in E. coli is disclosed. The fusion protein when administered to a host elicits a virus neutralizing antibody response which confers partial protection to the recipient animals against challenge infection. Sera from immunized mice revealed no neutralizing antibodies to any of the other DEN serotypes in the plaque reduction neutralization assay (PRNT). Excerpt(s): This invention relates to an immunologically active fusion protein, useful in vaccination against dengue (DEN) virus as well as a diagnostic antigen. More particularly, this invention relates to a fusion protein antigen containing 366 amino acids of a maltose binding protein (MBP) from E. coli fused to 103 amino acids of the DEN envelope protein. This fusion protein antigen reacts with mouse monoclonal (3H5) and polyclonal (HIAF) antibody to dengue virus as well as human anti-DEN antibody, making it a useful antigen for diagnostic assays and when administered as a vaccine, can confer protective immunity to a substantial proportion of vaccinated subjects. Prevention of DEN infections would alleviate a major health problem in tropical and subtropical areas of the world. Each of the four DEN serotypes may cause dengue fever and the more severe illnesses, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Infection with any one serotype of DEN appears to confer lifelong immunity to reinfection with the same serotype, but not to the other serotypes. Individuals sequentially infected with a different dengue serotype (secondary infection) appear to be at higher risk for developing more severe disease. Immmune enhancement has been proposed as the mechanism responsible for DHF/DSS. Because of this phenomenon, an effective vaccine must be either serotype specific or be against all four serotypes of dengue virus to insure that vaccination against a single serotype does not enhance infection with a different serotype. Despite more than 50 years of effort, safe and effective vaccines have not been developed. Attempts to produce cell culturederived live attenuated dengue vaccines by long term passage in primary kidney (PDK) cells were tried unsuccessfully (Ennis et al., J. Inf. Dis., 158:876-880, 1988). A dengue-1 candidate was shown to be genetically unstable (McKee et al., Am. J. Trop. Med. Hyg., 36(2):435-442, 1987). Other dengue 2, 3 and 4 candidates were also not suitable because they were either unstable, caused unmodified dengue fever or produced low levels of neutralizing antibody (Bancroft et al., J. Infect. Dis., 149:1005-1010, 1984, Hoke et al., Am.

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J. Trop. Med. Hyg., 43(2):219-226, 1990, Innis et al., Am. J. Trop. Med. Hyg., 40(6):676687, 1989). Web site: http://www.delphion.com/details?pn=US05895651__ •

Subunit immonogenic composition against dengue infection Inventor(s): Clements; David (Honolulu, HI), Ivy; John (Kailua, HI), Nakano; Eilen (Hon., HI) Assignee(s): Hawaii Biotechnology Group, Inc. (Aiea, HI) Patent Number: 6,165,477 Date filed: August 20, 1997 Abstract: The Flaviviridae comprise a number of medically important pathogens that cause significant morbidity in humans including the dengue (DEN) virus, Japanese encephalitis (JE) virus, tick-borne encephalitis virus (TBE), and yellow fever virus (YF). Flaviviruses are generally transmitted to vertebrates by chronically infected mosquito or tick vectors. The viral particle which is enveloped by host cell membranes, comprises a single positive strand genomic RNA and the structural capsid (CA), membrane (M), and envelope (E) proteins. The E and M proteins are found on the surface of the virion where they are anchored in the membrane. Mature E is glycosylated and contains functional domains responsible for cell surface attachment and intraendosomal fusion activities. Problems have arisen in the art with respect to producing recombinant forms of the E glycoprotein that retain their native configuration and attendant properties associated therewith (i.e., ability to induce neutralizing antibody responses). To date, recombinantly produced E glycoproteins have suffered from a number of limitations including improper glycosylation, folding, and disulfide bond formation. The claimed invention has addressed these concerns by providing secreted recombinant forms of the E glycoprotein that are highly immunogenic and appear to retain their native configuration. Carboxy-terminally truncated forms of E containing the amino terminal 395 amino acids and a suitable secretion signal sequence were generated in Drosophila melanogaster Schneider cell lines. Immunogenic compositions comprising these recombinant envelope glycoproteins were capable of inducing protective, neutralizing antibody responses when administered to a suitable host. Excerpt(s): The invention relates to protection against and diagnosis of dengue fever. More specifically, the invention concerns a subunit of the dengue virus envelope protein secreted as a mature recombinantly produced protein from eucaryotic cells which is protective against dengue infection, which raises antibodies useful in passive immunization, and which is useful in diagnosis of infection by the virus. The dengue viruses are members of the family Flaviviridae which also includes the Japanese encephalitis (JE) virus, Tick-borne encephalitis (TBE) virus, and the initially discovered prototype of this class, the yellow fever (YF) virus. The flaviviruses contain a single positive strand genomic RNA and are small enveloped viruses affecting animals, but generally transmitted to vertebrates by chronically infected mosquito or tick vectors. Flaviviruses are enveloped by host cell membrane and contain the three structural proteins capsid (C), membrane (M), and envelope (E). The E and M proteins are found on the surface of the virion where they are anchored in the membrane. Mature E is glycosylated, whereas M is not, although its precursor, prM, is a glycoprotein. Glycoprotein E, the largest structural protein, contains functional domains responsible for cell surface attachment and intraendosomal fusion activities. It is also a major target of the host immune system, inducing neutralizing antibodies, protective immunity, as

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well as antibodies which inhibit hemagglutination. Dengue virus is the causative agent of dengue fever and is transmitted to man by Aedes mosquitoes, principally Aedes aegypti and Aedes albopictus. Classic dengue fever is an acute illness marked by fever, headache, aching muscles and joints, and rash. A fraction of cases, typically in children, results in more extreme forms of infection, i.e., dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Without diagnosis and prompt medical intervention, the sudden onset and rapid progress of DHF/DSS can be fatal. Web site: http://www.delphion.com/details?pn=US06165477__

Patent Applications on Dengue Fever As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to dengue fever: •

Detection of dengue virus Inventor(s): Wang, Wei-Kung; (Taipei, TW) Correspondence: Y. Rocky Tsao; Fish & Richardson P.C.; 225 Franklin Street; Boston; MA; 02110-2804; US Patent Application Number: 20020155435 Date filed: February 28, 2002 Abstract: The present invention relates to a pair of dengue virus-specific primers for use in a reverse transcriptase-polymerase chain reaction to detect dengue virus. Excerpt(s): This application claims priority to U.S. provisional application No. 60/272,535 filed on Mar. 1, 2001, the contents of which are incorporated herein by reference. This invention relates to methods and reagents for detecting dengue viruses. Dengue virus, a member of flaviviruses, contains an 11 kb single-stranded RNA genome. Four different dengue virus subtypes have been identified, i.e., DEN-1, DEN-2, DEN-3, and DEN-4. The four subtypes are distributed among geographically distinct tropical and subtropical regions. All may cause diseases ranging from mild self-limited dengue fever (DF) to severe and potentially life-threatening dengue hemorrhagic fever/ dengue shock syndrome (DHF/DSS). Gubler, D. J. (1998) Clin. Microbiol. Rev. 11: 480496. Detection of dengue virus is crucial for rapid diagnosis, as well as for understanding of dengue virus pathogenesis. Innis, B. L. (1995) In J. S. Porterfield (Ed.), Exotic viral infections--1995. Chapman & Hall, London, pp103-146. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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This has been a common practice outside the United States prior to December 2000.

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Pro-apoptotic fragments of the dengue virus envelope glycoproteins Inventor(s): Catteau, Adeline; (Savigny Sur Orge, FR), Courageot, Marie-Pierre; (Paris, FR), Despres, Philippe; (La Garenne-Colombes, FR), Deubel, Vincent; (Vanves, FR) Correspondence: Oblon Spivak Mcclelland Maier & Neustadt PC; Fourth Floor; 1755 Jefferson Davis Highway; Arlington; VA; 22202; US Patent Application Number: 20020086403 Date filed: June 18, 2001 Abstract: The present invention relates to pro-apoptotic fragments of the Dengue virus pRM and E glycoproteins, methods of screening for molecules capable of inducing apoptosis and methods of inducing apoptosis in a cell. Excerpt(s): The present application claims priority to U.S. Provisional Application Ser. No. 60,212,129 filed Jun. 16, 2000, the entire contents of which are incorporated herein by reference. The present invention relates to fragments of the Dengue virus glycoproteins prM and E which induce apoptosis and can be used as a therapeutic agent against Flavivirus infection and cancer. In vivo infection of murine neurons and of human hepatocytes by the DEN virus induces cell death by apoptosis. In vitro, the induction of the apoptotic process by infection with the DEN-1 and DEN-2 viruses have been reproduced in murine neuroblastoma cells (Neuro 2a) and in human hepatoma cells (HepG2), in human Hela cells, CHO, 293T and the primate cell line VERO. We have formulated the hypothesis that accumulation of glycoproteins of the envelope of the DEN virus in the ER would lead to a stress which induces apoptosis. In the case of human hepatomas, this stress would lead to activation of the transcription factor NF.kappa.B, which would control the expression of pro-apoptotic genes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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RECOMBINANT MVA VIRUS EXPRESSING DENGUE VIRUS ANTIGENS, AND THE USE THEREOF IN VACCINES Inventor(s): CARDOSA, MARY JANE; (SARAWAK, MY), ERFLE, VOLKER; (MUNCHEN, DE), SUTTER, GERD; (MUNCHEN, DE) Correspondence: Antoinette Konski; Bingham Mccutchen, Llp; Three Embarcadero Center; Suite 1800; San Francisco; CA; 94111; US Patent Application Number: 20030082205 Date filed: March 23, 1999 Abstract: Recombinant MVA viruses containing and/or capable of expressing dengue virus antigens and the use of such recombinant MVA for vaccination. Excerpt(s): The present invention relates to recombinant vaccinia viruses derived from the modified vaccinia virus Ankara (MVA) encoding and capable of expressing dengue virus antigens, and the use of such recombinant MVA viruses encoding dengue virus antigens in vaccines. Dengue viruses are divided into four antigenically related serotypes, called dengue virus serotypes 1, 2, 3, and 4. Complete or partial nucleotide sequences of the dengue 1, 2, 3, and 4 type virus have been published (Chamber, T. J., Hahn, C. S., Galler, R. And Rice, C. M. 1990. Annu. Rev. Microbiol., 44, 649, Zhao et al., 1986, Virology 155, 77-88). Dengue virus, with its four serotypes Den-1 to Den-4, is the most important member of the Flavivirus genus with respect to infections of humans producing diseases that range from flu-like symptoms to severe or fatal illness, dengue

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haemorrhagic fever with shock syndrome. Dengue outbreaks continue to be a major public health problem in densely populated areas of the tropical and subtropical regions, where mosquito vectors are abundant. Therefore, there is a substantial need for the development of prophylactic vaccines. Previous efforts to prepare live candidate dengue vaccines were mainly based on classical attenuation of dengue virus by serial passage in animals or in cultured cells of non-natural hosts. However, this approach has not been consistently successful in producing attenuated vaccine strains. Available data indicate that recovery and protective immunity after dengue virus infection are correlated to the development of high titres of virus neutralising antibodies. However, this immunity is homotypic mediating resistance to the same virus serotype only. Moreover, individuals immune to one dengue virus serotype may be even at higher risk of developing severe dengue illness if reinfected with another serotype. To overcome these problems an ideal vaccine should therefore induce solid immunity against all four dengue virus serotypes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with dengue fever, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “dengue fever” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on dengue fever. You can also use this procedure to view pending patent applications concerning dengue fever. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 6. BOOKS ON DENGUE FEVER Overview This chapter provides bibliographic book references relating to dengue fever. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on dengue fever include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “dengue fever” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on dengue fever: •

Screening for Transmissible Diseases Source: Guidelines for the Organization of a Blood Transfusion Service. Contact: World Health Organization, Health Laboratory Technology and Blood Safety Unit, 20 Avenue Appia, 1211 Geneva 27. Summary: This book chapter discusses screening to prevent transmission of infectious diseases through blood and blood products. Topics covered are donor screening for viral hepatitis B, non-A non-B hepatitis, viral hepatitis C; delta agent; Human immunodeficiency virus (HIV), HIV variants such as HIV-2; syphilis and yaws; malaria; Chagas disease (American trypanosomiasis); cytomegalovirus (CMV); antigen testing; and "look-back" programs that trace seropositive donors to determine if they have previously given blood. It is also noted that microfilariae are not transmitted by blood transfusion, and that donors who have had diseases such as dengue fever,

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schistosomiasis, leptospirosis, yellow fever, or encephalitis are not permanently debarred from donating blood after their diseases have been cured.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “dengue fever” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “dengue fever” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “dengue fever” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Dengue and Dengue Hemorrahgic Fever by D. J. Gubler (Editor), et al; ISBN: 0851991343; http://www.amazon.com/exec/obidos/ASIN/0851991343/icongroupinterna

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Dengue and Dengue Hemorrhagic Fever in the Americas: Guidelines for Prevention and Control (Publicaciones Cientificas (Washington, D.C.), No. 548.) by Pan American Sanitary Bureau; ISBN: 9275115486; http://www.amazon.com/exec/obidos/ASIN/9275115486/icongroupinterna

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Dengue Fever (Epidemics) by Katherine White; ISBN: 0823942007; http://www.amazon.com/exec/obidos/ASIN/0823942007/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “dengue fever” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:10 •

Bibliography of dengue fever and dengue-like illnesses, 1780-1981 Author: Kuno, Goro.; Year: 1986; Noumea, New Caledonia: South Pacific Commission, 1982

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Bibliography on dengue and yellow fevers. Author: United States. Army. Chemical Corps. Technical Library.; Year: 1979; Frederick, Md., 1956

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In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Dengue fever: an environmental plague for the new millennium? Author: Lennox, Robert W.; Year: 1999; Arlington, Va.: EHP, [1999]

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Dengue fever studies in Malaysia Author: Rudnick, A. (Albert); Year: 1990; Kuala Lumpur, Malaysia: Institute for Medical Research, 1986

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Dengue fever surveillance: Vanuatu.; Year: 2000; [Port Vila: Ministry of Health, 1999.]

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Dengue haemorrhagic fever: diagnosis, treatment, and control. Author: World Health Organization.; Year: 1994; Geneva: World Health Organization Albany, NY: WHO Publications Center USA [distributor], 1986; ISBN: 9241542098 http://www.amazon.com/exec/obidos/ASIN/9241542098/icongroupinterna

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Dengue haemorrhagic fever in Thailand: geomedical observations on developments over the period 1970-1979 Author: Wellmer, Hella.; Year: 1971; Berlin; New York: Springer-Verlag, 1983; ISBN: 0387124861 http://www.amazon.com/exec/obidos/ASIN/0387124861/icongroupinterna

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Dengue hemorrhagic fever, 1981: proceedings of the First ICMR Seminar, November 21-22, 1980, Kobe, Japan. Author: Hotta, Susumu,; Year: 1985; Kobe, Japan: International Center for Medical Research, Kobe University School of Medicine, [1981?]

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DengueNet [electronic resource]: WHO global dengue surveillance Author: World Health Organization.; Year: 1975; Paris, France: Institute for Medical Research and Health, [2001?]-

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Fevers: including general considerations, typhoid fever, typhus fever, influenza, malarial fever, yellow fever, variola, relapsing fever, Weil's disease, thermic fever, dengue, miliary fever, mountain fever, etc. By James C. Wilson, M. D.; Solomon SolisCohen, M. D.; C. Meigs Wilson, M. D.; Augustus A. Eshner, M. D.; W. Reynolds Wilson, M. D.; Comp. from the Annual of the universal medical sciences, from 1888 to 1894, inclusive, by Augustus A. Eshner, M. D. With copious commentaries and additions. Embellished by wood-engravings and lithographs. Author: Eshner, Augustus Adolph,; Year: 1936; Philadelphia, F. A. Davis co.; London, F. J. Rebman, 1895

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International Conference on Dengue Haemorrhagic Fever: report of WHO; Year: 1895; [Geneva]: World Health Organization, [1994]

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Prevention of dengue fever: a manual for public health staff, nurses, health educators, and community development officers Author: Jabre, Bushra.; Year: 1994; Noumea, New Caledonia: South Pacific Commission, 1990; ISBN: 9822031564

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Review of epidemiologic research on dengue hemorrhagic fever in Indonesia Author: Noor, Nur Nasry.; Year: 1994; Jakarta: Badan Penelitian dan Pengembangan Kesehatan, Dep. Kes. R.i., 1985

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Singapore's dengue haemorrhagic fever control programme: a case study on the successful control of aedes aegypti and aedes albopictus using mainly environmental measures as a part of integrated vector control Author: Chan, Kai Lok,; Year: 1991; Tokyo: SEAMIC, 1985

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Strengthening implementation of the global strategy for dengue fever Author: World Health Organization. Parasitic Diseases and Vector Control.; Year: 2000; Geneva: World Health Organization, Communicable Disease Control, Prevention, and Eradication, Parasitic Diseases and Vector Control, [2000]

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Technical guides for diagnosis, treatment, surveillance, prevention and control of dengue haemorrhagic fever Author: World Health Organization. Technical Advisory Committee on Dengue Haemorrhagic Fever for the South-East Asian and Western Pacific Regions.; Year: 1975; Geneva: The Committee, 1975

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The transmission of dengue fever in Puerto Rico: an epidemiologic approach using a Geographic Information System Author: Morrison, Amy C.; Year: 1999; San Juan, P.R. (651 Federal Drive, Guaynabo 00965-5703): U.S. Dept. of the Interior, U.S. Geological Survey; Denver, CO: Branch of Information Services [distributor], 1998

Chapters on Dengue Fever In order to find chapters that specifically relate to dengue fever, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and dengue fever using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “dengue fever” (or synonyms) into the “For these words:” box.

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CHAPTER 7. MULTIMEDIA ON DENGUE FEVER Overview In this chapter, we show you how to keep current on multimedia sources of information on dengue fever. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Bibliography: Multimedia on Dengue Fever The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in dengue fever (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on dengue fever: •

DengueNet [electronic resource]: WHO global dengue surveillance Source: TDR, Inserm, NASA; Year: 9999; Format: Electronic resource; Paris, France: Institute for Medical Research and Health, [2001?]-

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It's up to you [motion picture]: dengue-yellow fever control Source: produced by U.S. Public Health Service, Office of Malaria Control in War Areas; Year: 1945; Format: Motion picture; United States: The Service, [1945]

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CHAPTER 8. PERIODICALS AND NEWS ON DENGUE FEVER Overview In this chapter, we suggest a number of news sources and present various periodicals that cover dengue fever.

News Services and Press Releases One of the simplest ways of tracking press releases on dengue fever is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “dengue fever” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to dengue fever. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “dengue fever” (or synonyms). The following was recently listed in this archive for dengue fever: •

Dengue kills 83; more than 5,000 ill across India Source: Reuters Health eLine Date: October 10, 2003

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Dengue kills 83 and infects more than 5,000 across India Source: Reuters Medical News Date: October 10, 2003

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Dengue fever cases increasing in Germany Source: Reuters Health eLine Date: July 03, 2003

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Dengue cases increasing in Germany Source: Reuters Medical News Date: July 03, 2003

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T cells responses to initial dengue infection impede subsequent viral clearance Source: Reuters Medical News Date: June 16, 2003

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Scientists crack dengue fever puzzle Source: Reuters Health eLine Date: June 16, 2003

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Hemorrhagic dengue epidemic grips Ecuador Source: Reuters Health eLine Date: February 20, 2003

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Maxygen seeking partner to help complete dengue vaccine development Source: Reuters Industry Breifing Date: December 05, 2002

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Taiwan military called in to battle dengue fever Source: Reuters Health eLine Date: November 19, 2002

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Military assistance called in to contain dengue fever in Taiwan Source: Reuters Medical News Date: November 19, 2002

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Public efforts begin to halt Taiwan dengue outbreak Source: Reuters Health eLine Date: November 11, 2002

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Hong Kong unveils plan to tackle dengue as fear spreads Source: Reuters Medical News Date: October 10, 2002

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Hong Kong unveils anti-dengue plan as fear spreads Source: Reuters Health eLine Date: October 10, 2002

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Hong Kong reports first case of locally contracted dengue Source: Reuters Medical News Date: September 23, 2002

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Hong Kong has 1st case of locally contracted dengue Source: Reuters Health eLine Date: September 23, 2002

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Singapore battles rise in dengue fever cases Source: Reuters Health eLine Date: September 09, 2002

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Malaria, dengue fever kill nearly 500 Bangladeshis Source: Reuters Health eLine Date: August 20, 2002

Periodicals and News

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Bangladesh urges on-leave physicians to return to fight dengue outbreak Source: Reuters Medical News Date: August 13, 2002

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All hands needed to fight Bangladesh dengue flareup Source: Reuters Health eLine Date: August 13, 2002

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Dengue fever kills 16 in Bangladesh Source: Reuters Health eLine Date: August 08, 2002

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WHO issues dengue fever warning Source: Reuters Health eLine Date: July 29, 2002

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US travelers to tropics continue to contract dengue fever Source: Reuters Medical News Date: April 04, 2002

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Dengue fever outbreak strikes Easter Island Source: Reuters Health eLine Date: March 20, 2002

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Dengue mosquito becomes Brazil's public enemy No.1 Source: Reuters Health eLine Date: February 27, 2002

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Dengue epidemic grows ahead of Rio Carnival Source: Reuters Medical News Date: February 04, 2002

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Rio fights dengue outbreak as Carnival looms Source: Reuters Health eLine Date: February 01, 2002

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Brazil dengue epidemic kills 5, thousands sick Source: Reuters Health eLine Date: January 25, 2002

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Singapore dengue test uses DNA to spot virus early Source: Reuters Health eLine Date: January 22, 2002

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DNA test may allow early diagnosis of Dengue fever Source: Reuters Industry Breifing Date: January 22, 2002

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Dengue outbreak hits Rio, at least one dead Source: Reuters Medical News Date: January 21, 2002

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Dengue outbreak hits Rio, kills at least one Source: Reuters Health eLine Date: January 18, 2002

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Cuba battling biggest dengue outbreak since 1981 Source: Reuters Health eLine Date: January 14, 2002

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Dengue fever outbreak in Hawaii first in 50 years Source: Reuters Health eLine Date: October 09, 2001

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Dengue outbreak threatens Macau as cases soar Source: Reuters Health eLine Date: October 03, 2001

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Macau dengue outbreak triggers alert in Hong Kong Source: Reuters Health eLine Date: August 30, 2001

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Venezuela, facing epidemic, declares war on dengue Source: Reuters Health eLine Date: August 23, 2001

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CDC encourages awareness of dengue fever Source: Reuters Medical News Date: February 01, 2001

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Dengue Fever Kills 47 in Bangladesh Source: Reuters Health eLine Date: August 29, 2000

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El Salvador asks US for help in dengue epidemic Source: Reuters Health eLine Date: August 09, 2000

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Dengue fever kills 28 in Bangladesh; hundreds sick Source: Reuters Medical News Date: August 08, 2000

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Bangladesh strike called off over dengue concerns Source: Reuters Health eLine Date: August 04, 2000

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Dengue fever kills four in Bangladesh capital Source: Reuters Health eLine Date: July 25, 2000

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Dengue fever could worsen in 21st century. Source: Reuters Health eLine Date: April 12, 2000

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Dengue fever on the rise in US Source: Reuters Health eLine Date: March 31, 2000

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Paraguay faces outbreak of dengue fever Source: Reuters Health eLine Date: March 10, 2000

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Texas girl dies from dengue fever Source: Reuters Health eLine Date: December 27, 1999

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Dengue fever being imported into Florida Source: Reuters Medical News Date: December 23, 1999

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Dengue fever cases found in Florida Source: Reuters Health eLine Date: December 22, 1999

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Blood type B predicts bleeding in dengue fever Source: Reuters Medical News Date: November 11, 1999

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Blood type may predict bleeding risk in Dengue fever Source: Reuters Health eLine Date: November 10, 1999

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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “dengue fever” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “dengue fever” (or synonyms). If you know the name of a company that is relevant to dengue fever, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.

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BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “dengue fever” (or synonyms).

Academic Periodicals covering Dengue Fever Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to dengue fever. In addition to these sources, you can search for articles covering dengue fever that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 9. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for dengue fever. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with dengue fever. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

102 Dengue Fever

following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to dengue fever: Headache Medicines, Ergot Derivative-Containing •

Systemic - U.S. Brands: Cafergot; Cafertine; Cafetrate; D.H.E. 45; Ercaf; ErgoCaff; Ergomar; Ergostat; Gotamine; Migergot; Wigraine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202216.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

105

APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute11: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

11

These publications are typically written by one or more of the various NIH Institutes.

106 Dengue Fever

•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:13 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

12

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 13 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “dengue fever” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 2696 87 390 10 0 3183

HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.18 Simply search by “dengue fever” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

14

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

15

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

19 Adapted 20

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on dengue fever can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to dengue fever. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to dengue fever. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “dengue fever”:

112 Dengue Fever

•

Guides on dengue fever Dengue http://www.nlm.nih.gov/medlineplus/dengue.html

•

Other guides Bone Cancer http://www.nlm.nih.gov/medlineplus/bonecancer.html Brain Diseases http://www.nlm.nih.gov/medlineplus/braindiseases.html Cartilage Disorders http://www.nlm.nih.gov/medlineplus/cartilagedisorders.html Encephalitis http://www.nlm.nih.gov/medlineplus/encephalitis.html Hemorrhagic Fevers http://www.nlm.nih.gov/medlineplus/hemorrhagicfevers.html Insect Bites and Stings http://www.nlm.nih.gov/medlineplus/insectbitesandstings.html Lupus http://www.nlm.nih.gov/medlineplus/lupus.html Malaria http://www.nlm.nih.gov/medlineplus/malaria.html Meningitis http://www.nlm.nih.gov/medlineplus/meningitis.html Movement Disorders http://www.nlm.nih.gov/medlineplus/movementdisorders.html Neurologic Diseases http://www.nlm.nih.gov/medlineplus/neurologicdiseases.html Osteogenesis Imperfecta http://www.nlm.nih.gov/medlineplus/osteogenesisimperfecta.html Osteoporosis http://www.nlm.nih.gov/medlineplus/osteoporosis.html Parasitic Diseases http://www.nlm.nih.gov/medlineplus/parasiticdiseases.html Tick Bites http://www.nlm.nih.gov/medlineplus/tickbites.html West Nile Virus http://www.nlm.nih.gov/medlineplus/westnilevirus.html

Patient Resources

Within the health topic page dedicated to dengue fever, the following was listed: •

General/Overviews Dengue and Dengue Haemorrhagic Fever Source: World Health Organizations http://www.who.int/inf-fs/en/fact117.html Dengue and Dengue Hemorrhagic Fever: Questions and Answers Source: National Center for Infectious Diseases http://www.cdc.gov/ncidod/dvbid/dengue/dengue-qa.htm

•

Specific Conditions/Aspects Dengue Fever Information for Travelers Source: National Center for Infectious Diseases http://www.cdc.gov/travel/dengfvr.htm

•

From the National Institutes of Health Dengue Fever Source: National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/factsheets/dengue.htm

•

Organizations National Center for Infectious Diseases http://www.cdc.gov/ncidod/index.htm National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/ World Health Organization http://www.who.int/en/

•

Prevention/Screening Mosquito Repellents: To DEET or Not to DEET Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=FL00083 Preventing Dengue and Dengue Hemmorhagic Fever Source: National Center for Infectious Diseases http://www.cdc.gov/ncidod/dvbid/dengue/denguespot2003.htm

•

Research Dengue Source: National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/newsroom/focuson/bugborne01/dengue.htm

•

Statistics World Distribution of Dengue - 2000 Source: National Center for Infectious Diseases http://www.cdc.gov/ncidod/dvbid/dengue/map-distribution-2000.htm

113

114 Dengue Fever

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to dengue fever. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to dengue fever. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with dengue fever. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about dengue fever. For more information, see

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the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “dengue fever” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “dengue fever”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “dengue fever” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “dengue fever” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.22

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

22

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

118 Dengue Fever

libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)23: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

23

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries

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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on dengue fever: •

Basic Guidelines for Dengue Fever Dengue fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001374.htm Dengue hemorrhagic fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001373.htm

•

Signs & Symptoms for Dengue Fever Arthralgia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003261.htm Convulsions Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Decreased appetite Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003121.htm

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Ecchymoses Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003235.htm Enlarged liver Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003275.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Headache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003024.htm Hepatomegaly Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003275.htm Joint aches Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003261.htm Joint pains Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003261.htm Low blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003083.htm Malaise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003089.htm Muscle Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Muscle aches Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003178.htm Muscle pains Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003178.htm Myalgia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003178.htm Petechiae Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003235.htm Rapid pulse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003077.htm Rash Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Rashes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm

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Restless Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003212.htm Restlessness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003212.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm •

Diagnostics and Tests for Dengue Fever Antibody titer Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003333.htm CBC Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm Electrolyte imbalances Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003468.htm Hematocrit Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003646.htm Platelets Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003647.htm Tourniquet test Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003395.htm X-ray of the chest Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003804.htm

•

Background Topics for Dengue Fever Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm Antibodies Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002223.htm Antigen Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002224.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Electrolytes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002350.htm Endemic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002362.htm

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Immunity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000821.htm Intravenous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002383.htm Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm Shock Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000039.htm Titer Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002328.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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DENGUE FEVER DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aedes: A genus of mosquitoes (culicidae) frequently found in tropical and subtropical regions. yellow fever and dengue are two of the diseases that can be transmitted by species of this genus. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the

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tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Alphavirus: A genus of Togaviridae, also known as Group A arboviruses, serologically related to each other but not to other Togaviridae. The viruses are transmitted by mosquitoes. The type species is the sindbis virus. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in

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the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anthrax: An acute bacterial infection caused by ingestion of bacillus organisms. Carnivores may become infected from ingestion of infected carcasses. It is transmitted to humans by contact with infected animals or contaminated animal products. The most common form in humans is cutaneous anthrax. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH]

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Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues. [NIH] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arbovirus Infections: Infections caused by arthropod-borne viruses, general or unspecified. [NIH]

Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arthralgia: Pain in the joint. [NIH] Arthropod Vectors: Arthropods, other than insects and arachnids, which transmit infective organisms from one host to another or from an inanimate reservoir to an animate host. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Ascitic Fluid: The serous fluid which accumulates in the peritoneal cavity in ascites. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH]

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Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bioterrorism: The use of biological agents in terrorism. This includes the malevolent use of bacteria, viruses, or toxins against people, animals, or plants. [NIH] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Biphasic: Having two phases; having both a sporophytic and a gametophytic phase in the life cycle. [EU] Bladder: The organ that stores urine. [NIH]

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Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood transfusion: The administration of blood or blood products into a blood vessel. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]

Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary

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for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carcinogenic: Producing carcinoma. [EU] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Catalyse: To speed up a chemical reaction. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH]

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Chemotherapy: Treatment with anticancer drugs. [NIH] Chickenpox: A mild, highly contagious virus characterized by itchy blisters all over the body. [NIH] Chimera: An individual that contains cell populations derived from different zygotes. [NIH] Chimeric Proteins: Proteins in individuals that are derived from genetically different zygotes. [NIH] Chitin Synthase: An enzyme that converts UDP glucosamine into chitin and UDP. EC 2.4.1.16. [NIH] Cholecystitis: Inflammation of the gallbladder. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Colloidal: Of the nature of a colloid. [EU] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix

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'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Compress: A plug used to occludate an orifice in the control of bleeding, or to mop up secretions; an absorbent pad. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known conserved sequence set is represented by a consensus sequence. Commonly observed supersecondary protein structures (amino acid motifs) are often formed by conserved sequences. [NIH] Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a consensus sequence. Amino acid motifs are often composed of conserved sequences. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Consumption: Pulmonary tuberculosis. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH]

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Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cowpox: A mild, eruptive skin disease of milk cows caused by cowpox virus, with lesions occurring principally on the udder and teats. Human infection may occur while milking an infected animal. [NIH] Cowpox Virus: A species of orthopoxvirus that is the etiologic agent of cowpox. It is closely related to but antigenically different from vaccina virus. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytotoxic: Cell-killing. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or

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involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Dengue Virus: A species of the genus Flavivirus which causes an acute febrile and sometimes hemorrhagic disease in man. Dengue is mosquito-borne and four serotypes are known. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dilatation: The act of dilating. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Transmission: The transmission of infectious disease or pathogens. When

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transmission is within the same species, the mode can be horizontal (disease transmission, horizontal) or vertical (disease transmission, vertical). [NIH] Disease Transmission, Horizontal: The transmission of infectious disease or pathogens from one individual to another in the same generation. [NIH] Disease Transmission, Vertical: The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding. [NIH] Disease Vectors: Invertebrates or non-human vertebrates which transmit infective organisms from one host to another. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU]

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Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis Viruses: A collection of single-stranded RNA viruses scattered across the Bunyaviridae, Flaviviridae, and Togaviridae families whose common property is the ability to induce encephalitic conditions in infected hosts. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalocele: Cerebral tissue herniation through a congenital or acquired defect in the skull. The majority of congenital encephaloceles occur in the occipital or frontal regions. Clinical features include a protuberant mass that may be pulsatile. The quantity and location of protruding neural tissue determines the type and degree of neurologic deficit. Visual defects, psychomotor developmental delay, and persistent motor deficits frequently occur. [NIH]

Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured

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spectrophotometrically or with the naked eye. Many variations of the method have been developed. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extracellular: Outside a cell or cells. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fatal Outcome: Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from death, the physiological cessation of life and from mortality, an epidemiological or statistical concept. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fever of Unknown Origin: Fever in which the etiology cannot be ascertained. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filariasis: Infections with nematodes of the superfamily Filarioidea. The presence of living worms in the body is mainly asymptomatic but the death of adult worms leads to granulomatous inflammation and permanent fibrosis. Organisms of the genus Elaeophora infect wild elk and domestic sheep causing ischaemic necrosis of the brain, blindness, and

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dermatosis of the face. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flavivirus: A genus of Flaviviridae, also known as Group B arbovirus, containing several subgroups and species. Most are arboviruses transmitted by mosquitoes or ticks. The type species is yellow fever virus. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gametogenesis: The first phase of sexual reproduction which involves the transforming of certain cells in the parent into specialized reproductive cells. [NIH] Gangrenous: A circumscribed, deep-seated, suppurative inflammation of the subcutaneous tissue of the eyelid discharging pus from several points. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used

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in a radiopharmaceutical. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]

Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH]

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Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH] Haematoma: A localized collection of blood, usually clotted, in an organ, space, or tissue, due to a break in the wall of a blood vessel. [EU] Haemoptysis: The expectoration of blood or of blood-stained sputum. [EU] Haemorrhage: The escape of blood from the vessels; bleeding. Small haemorrhages are classified according to size as petechiae (very small), purpura (up to 1 cm), and ecchymoses (larger). The massive accumulation of blood within a tissue is called a haematoma. [EU] Hantavirus: A genus of the family Bunyaviridae causing Hantavirus infections, first identified during the Korean war. Infection is found primarily in rodents and humans. Transmission does not appear to involve arthropods. The genus has one recognized group (Hantaan group) consisting of several species including Dobrava-Belgrade virus, Seoul virus, Prospect Hill virus, Puumala virus, Thottapalayam virus, and Hantaan virus, the type species. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Hemocytes: Any blood or formed element especially in invertebrates. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatoma: A liver tumor. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the

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formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homotypic: Adhesion between neutrophils. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been

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immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogen: A substance that is capable of causing antibody formation. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic

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clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH] Insect Vectors: Insects that transmit infective organisms from one host to another or from an inanimate reservoir to an animate host. [NIH] Insect Viruses: Viruses infecting insects, the largest family being Baculoviridae. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intravenous: IV. Into a vein. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Invertebrates: Animals that have no spinal column. [NIH] Isoelectric: Separation of amphoteric substances, dissolved in water, based on their

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isoelectric behavior. The amphoteric substances are a mixture of proteins to be separated and of auxiliary "carrier ampholytes". [NIH] Isoelectric Point: The pH in solutions of proteins and related compounds at which the dipolar ions are at a maximum. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Kilobase: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Leptospira: A genus of aerobic, helical spirochetes, some species of which are pathogenic, others free-living or saprophytic. [NIH] Leptospirosis: Infections with bacteria of the genus Leptospira. [NIH] Lethal: Deadly, fatal. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH]

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Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphocyte Subsets: A classification of lymphocytes based on structurally or functionally different populations of cells. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokine: A soluble protein produced by some types of white blood cell that stimulates other white blood cells to kill foreign invaders. [NIH] Lysosome: A sac-like compartment inside a cell that has enzymes that can break down cellular components that need to be destroyed. [NIH] Lyssavirus: A genus of the family Rhabdoviridae that includes rabies virus and other rabieslike viruses. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malaise: A vague feeling of bodily discomfort. [EU] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH]

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Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Measles Virus: The type species of morbillivirus and the cause of the highly infectious human disease measles, which affects mostly children. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fusion: The adherence of cell membranes, intracellular membranes, or artifical membrane models of either to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Mental Health: The state wherein the person is well adjusted. [NIH] Metaphase: The second phase of cell division, in which the chromosomes line up across the equatorial plane of the spindle prior to separation. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU]

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Molecular Evolution: Multiple rounds of selection, amplification, and mutation leading to molecules with the desired properties. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morbillivirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the virions have hemagglutinin but not neuraminidase activity. All members produce both cytoplasmic and intranuclear inclusion bodies. MEASLES VIRUS is the type species. [NIH]

Morphological: Relating to the configuration or the structure of live organs. [NIH] Mosquito Control: The reduction or regulation of the population of mosquitoes through chemical, biological, or other means. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Mumps Virus: The type species of rubulavirus that causes an acute infectious disease in humans, affecting mainly children. Transmission occurs by droplet infection. [NIH] Mung bean: A type of bean grown in warm climates. It is usually used for its seed and for bean sprouts. Mung bean may have anticancer effects. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH]

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Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural tube defects: These defects include problems stemming from fetal development of the spinal cord, spine, brain, and skull, and include birth defects such as spina bifida, anencephaly, and encephalocele. Neural tube defects occur early in pregnancy at about 4 to 6 weeks, usually before a woman knows she is pregnant. Many babies with neural tube defects have difficulty walking and with bladder and bowel control. [NIH] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurologic Manifestations: Clinical signs and symptoms caused by nervous system injury or dysfunction. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neutralization: An act or process of neutralizing. [EU] Neutralization Tests: Titration of an antiserum by testing a series of dilutions of virus or immune serum to a given end-point, which is generally the dilution at which tissue cultures inoculated with the serum-virus mixtures demonstrate cytopathology (CPE) or the dilution at which 50% of test animals injected with serum-virus mixtures show infectivity (ID50) or die (LD50). [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the

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information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleocapsid: A protein-nucleic acid complex which forms part or all of a virion. It consists of a capsid plus enclosed nucleic acid. Depending on the virus, the nucleocapsid may correspond to a naked core or be surrounded by a membranous envelope. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Oogenesis: The formation, development, and maturation of the female germ cell. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which

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may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parasitic Diseases: Infections or infestations with parasitic organisms. They are often contracted through contact with an intermediate vector, but may occur as the result of direct exposure. [NIH] Particle: A tiny mass of material. [EU] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perennial: Lasting through the year of for several years. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Petechiae: Pinpoint, unraised, round red spots under the skin caused by bleeding. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the

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formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Polyarthritis: An inflammation of several joints together. [EU] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH]

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Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH]

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Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH]

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Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Rabies: A highly fatal viral infection of the nervous system which affects all warm-blooded animal species. It is one of the most important of the zoonoses because of the inevitably fatal outcome for the infected human. [NIH] Rabies Virus: The type species of lyssavirus causing rabies in humans and other animals. Transmission is mostly by animal bites through saliva. The virus is neurotropic multiplying in neurons and myotubes of vertebrates. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radioactive: Giving off radiation. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Receptivity: The condition of the reproductive organs of a female flower that permits effective pollination. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Replicon: In order to be replicated, DNA molecules must contain an origin of duplication and in bacteria and viruses there is usually only one per genome. Such molecules are called replicons. [NIH] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH]

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Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhinovirus: A genus of Picornaviridae inhabiting primarily the respiratory tract of mammalian hosts. It includes the human strains associated with common colds. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rubella: An acute, usually benign, infectious disease caused by a togavirus and most often affecting children and nonimmune young adults, in which the virus enters the respiratory tract via droplet nuclei and spreads to the lymphatic system. It is characterized by a slight cold, sore throat, and fever, followed by enlargement of the postauricular, suboccipital, and cervical lymph nodes, and the appearances of a fine pink rash that begins on the head and spreads to become generalized. Called also German measles, roetln, röteln, and three-day measles, and rubeola in French and Spanish. [EU] Rubulavirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the species have hemagglutinin and neuraminidase activities but lack a C protein. Mumps virus is the type species. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponin: A substance found in soybeans and many other plants. Saponins may help lower cholesterol and may have anticancer effects. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH]

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Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Septicaemia: A term originally used to denote a putrefactive process in the body, but now usually referring to infection with pyogenic micro-organisms; a genus of Diptera; the severe type of infection in which the blood stream is invaded by large numbers of the causal. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serial Passage: Inoculation of a series of animals or in vitro tissue with an infectious bacterium or virus, as in virulence studies and the development of vaccines. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled

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to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sindbis Virus: The type species of alphavirus normally transmitted to birds by Culex mosquitoes in Egypt, South Africa, India, Malaya, the Philippines, and Australia. It may be associated with fever in humans. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Smallpox: A generalized virus infection with a vesicular rash. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spina bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [NIH]

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Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptavidin: A 60kD extracellular protein of Streptomyces avidinii with four high-affinity biotin binding sites. Unlike AVIDIN, streptavidin has a near neutral isoelectric point and is free of carbohydrate side chains. [NIH] Streptococci: A genus of spherical Gram-positive bacteria occurring in chains or pairs. They are widely distributed in nature, being important pathogens but often found as normal commensals in the mouth, skin, and intestine of humans and other animals. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

Systemic: Affecting the entire body. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Tetravalent: Pertaining to a group of 4 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU]

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Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Ticks: Blood-sucking arachnids of the order Acarina. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Tourniquet: A device, band or elastic tube applied temporarily to press upon an artery to stop bleeding; a device to compress a blood vessel in order to stop bleeding. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Transaminase: Aminotransferase (= a subclass of enzymes of the transferase class that catalyse the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally 2-keto acid). Most of these enzymes are pyridoxal-phosphate-proteins. [EU]

Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH]

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Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Transposons: Discrete genetic elements capable of inserting, in a non-permuted fashion, into the chromosomes of many bacteria. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Trophic: Of or pertaining to nutrition. [EU] Trypanosomiasis: Infection with protozoa of the genus Trypanosoma. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tsetse Flies: Bloodsucking flies of the genus Glossina, found primarily in equatorial Africa. Several species are intermediate hosts of trypanosomes. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH]

164 Dengue Fever

Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vaccinia Virus: The type species of Orthopoxvirus, related to cowpox virus, but whose true origin is unknown. It has been used as a live vaccine against smallpox. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of vaccinia virus. [NIH] Variola: A generalized virus infection with a vesicular rash. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venous: Of or pertaining to the veins. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viraemia: The presence of virus in blood or blood plasma. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [NIH] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Viremia: The presence of viruses in the blood. [NIH] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH]

Dictionary 165

Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of proteins, nucleic acids, and sometimes lipids, and their assembly into a new infectious particle. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Vitamin D: The vitamin that mediates intestinal calcium absorption, bone calcium metabolism, and probably muscle activity. It usually acts as a hormone precursor, requiring 2 stages of metabolism before reaching actual hormonal form. It is isolated from fish liver oils and used in the treatment and prevention of rickets. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] War: Hostile conflict between organized groups of people. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

World Health: The concept pertaining to the health status of inhabitants of the world. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yaws: A systemic non-venereal infection of the tropics caused by Treponema pallidum subspecies pertenue. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yellow Fever: An acute infectious disease primarily of the tropics, caused by a virus and transmitted to man by mosquitoes of the genera Aedes and Haemagogus. [NIH] Yellow Fever Vaccine: Vaccine used to prevent yellow fever. It consists of a live attenuated 17D strain of the yellow fever virus. [NIH] Yellow Fever Virus: The type species of the Flavivirus genus. Principal vector transmission to humans is by Aedes spp. mosquitoes. [NIH] Zoonoses: Diseases of non-human animals that may be transmitted to man or may be transmitted from man to non-human animals. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

167

INDEX A Abdomen, 127, 132, 146, 147, 153, 160, 161 Abdominal, 57, 127, 152, 153 Aberrant, 65, 127 Acceptor, 127, 152, 162, 163 Acquired Immunodeficiency Syndrome, 78, 127 Adaptability, 5, 127, 133 Adaptation, 17, 127 Adenovirus, 4, 127 Adjustment, 127 Adjuvant, 21, 127, 141 Adverse Effect, 127, 159 Aedes, 5, 6, 7, 10, 12, 13, 15, 17, 19, 21, 23, 24, 35, 36, 68, 77, 82, 85, 91, 127, 165 Aerobic, 127, 147 Aerosol, 38, 127 Affinity, 127, 160, 161 Agar, 128, 154 Algorithms, 128, 131 Alleles, 8, 9, 13, 14, 20, 128 Alphavirus, 6, 16, 128, 160 Alternative medicine, 99, 128 Amino Acid Sequence, 54, 81, 128, 129, 135, 142 Amino Acids, 9, 21, 22, 30, 83, 84, 128, 135, 142, 153, 154, 156, 158, 159, 163 Ammonia, 128, 142 Amplification, 16, 28, 29, 78, 80, 128, 150 Anaesthesia, 128, 145 Anal, 128, 140, 141 Analogous, 128, 162 Anaphylatoxins, 128, 135 Anemia, 129, 148 Anesthesia, 129, 155 Animal model, 4, 7, 14, 21, 74, 79, 129 Annealing, 129, 154 Anthrax, 4, 129 Antibacterial, 129, 160 Antibiotic, 129, 160 Antibodies, 7, 9, 11, 26, 27, 28, 29, 44, 47, 76, 79, 80, 81, 83, 84, 87, 125, 129, 130, 144, 148, 150, 154 Anticoagulant, 129, 156 Antigen, 9, 26, 28, 53, 76, 83, 89, 125, 128, 129, 130, 135, 137, 139, 144, 145, 159 Antigen-Antibody Complex, 129, 135 Antigen-presenting cell, 9, 129, 137

Anti-inflammatory, 51, 129, 137, 142 Antioxidants, 58, 130 Antiserum, 130, 151 Antiviral, 22, 44, 130, 146 Apoptosis, 26, 86, 130 Aqueous, 130, 131, 136, 138, 147 Arbovirus Infections, 15, 130 Arterial, 130, 144, 156 Arteries, 130, 132, 136, 149 Arterioles, 130, 132 Arthralgia, 79, 123, 130 Arthropod Vectors, 6, 130 Ascites, 130 Ascitic Fluid, 83, 130 Assay, 7, 9, 10, 12, 16, 19, 20, 27, 28, 30, 32, 53, 78, 83, 130, 145 Asymptomatic, 130, 140 Attenuated, 7, 26, 27, 31, 74, 75, 80, 83, 87, 130, 137, 165 Attenuation, 74, 75, 87, 130 Atypical, 34, 130 B Bacillus, 129, 130 Bacteria, 129, 130, 131, 139, 140, 147, 149, 154, 157, 160, 161, 162, 163, 164 Bacterial Physiology, 127, 130 Bacteriophage, 130, 154, 162 Bacterium, 131, 159 Base, 131, 137, 142, 147, 161 Basophils, 131, 143, 147 Benign, 54, 131, 143, 151, 158, 165 Bile, 131, 141, 144, 147 Binding Sites, 131, 161 Biochemical, 7, 12, 13, 15, 22, 24, 52, 58, 128, 131, 142, 159 Biological Markers, 75, 131 Biological response modifier, 131, 146 Biomarkers, 18, 131 Biosynthesis, 131, 155, 159 Biotechnology, 25, 32, 81, 84, 90, 99, 107, 131 Bioterrorism, 4, 11, 131 Biotin, 64, 131, 161 Biphasic, 79, 131 Bladder, 131, 151, 155 Blood Platelets, 132, 159, 162 Blood pressure, 124, 132, 144, 150, 160 Blood transfusion, 89, 132

168 Dengue Fever

Blood vessel, 132, 139, 143, 148, 162, 164 Body Fluids, 131, 132, 160, 163 Bolus, 7, 132 Bolus infusion, 132 Bone Marrow, 132, 145, 148, 150 Bowel, 128, 132, 146, 151 Branch, 29, 92, 121, 132, 148, 153, 156, 160, 161 Breakdown, 132, 137 Breeding, 17, 132 Buccal, 132, 147 C Calcium, 132, 134, 159, 165 Capillary, 77, 132, 164 Capsid, 54, 80, 82, 84, 132, 152, 164 Carbohydrate, 132, 142, 154, 161 Carbon Dioxide, 132, 141, 158 Carboxy, 82, 84, 133 Carcinogenic, 133, 146, 155 Case report, 27, 32, 42, 56, 60, 133, 140 Catalyse, 133, 162 Cell Death, 86, 130, 133, 150 Cell Differentiation, 133, 159 Cell Division, 130, 133, 149, 154, 155, 159 Cell membrane, 10, 16, 84, 133, 137, 149 Cell proliferation, 64, 133, 159 Cellulose, 133, 154 Central Nervous System, 26, 51, 133, 142, 143, 159 Central Nervous System Infections, 133, 143 Cerebrospinal, 47, 133 Cerebrospinal fluid, 47, 133 Cervical, 133, 158 Chemokines, 4, 26, 133 Chemotactic Factors, 133, 135 Chemotherapy, 22, 33, 35, 134 Chickenpox, 78, 134 Chimera, 7, 31, 134 Chimeric Proteins, 81, 134 Chitin Synthase, 7, 134 Cholecystitis, 34, 44, 134 Cholera, 134, 159 Cholesterol, 131, 134, 147, 158 Chromatin, 130, 134, 140, 151 Chromosomal, 13, 128, 134, 154 Chromosome, 13, 23, 134, 143, 147, 159 Chronic, 134, 145, 161 Clinical Medicine, 134, 155 Clinical trial, 3, 7, 21, 107, 134, 156, 157 Clone, 10, 12, 13, 15, 134 Cloning, 131, 134

Cofactor, 134, 156, 162 Colloidal, 134, 138 Complement, 18, 38, 82, 129, 134, 135, 148 Complementary and alternative medicine, 67, 69, 135 Complementary medicine, 67, 135 Compress, 135, 162 Computational Biology, 107, 135 Conjugated, 81, 135 Conjunctiva, 135, 146 Conjunctivitis, 78, 135 Consensus Sequence, 135 Conserved Sequence, 19, 135 Constitutional, 79, 135 Consumption, 135, 137, 158 Contraindications, ii, 135 Coronary, 136, 149 Coronary Thrombosis, 136, 149 Corticosteroids, 136, 142 Cortisone, 136, 137 Cowpox, 136, 164 Cowpox Virus, 136, 164 Cranial, 136, 143 Craniocerebral Trauma, 136, 143 Crossing-over, 136, 157 Cultured cells, 87, 136 Curative, 78, 136, 151, 158, 161 Cutaneous, 129, 136, 147, 164 Cysteine, 133, 136, 139 Cytokine, 15, 26, 32, 37, 136 Cytomegalovirus, 89, 136 Cytoplasm, 16, 130, 131, 133, 136, 140, 143, 150, 151, 158 Cytotoxic, 9, 26, 30, 44, 136, 160 D Databases, Bibliographic, 107, 136 Defense Mechanisms, 15, 25, 136 Degenerative, 136, 143 Deletion, 130, 137 Dementia, 127, 137 Denaturation, 137, 154 Dendrites, 137, 151 Dendritic, 9, 10, 29, 137 Dendritic cell, 9, 10, 137 Density, 8, 137, 147, 152 Depolarization, 137, 160 Dermatosis, 137, 141 Developed Countries, 13, 78, 137 Developing Countries, 16, 27, 78, 137 Dexamethasone, 78, 137 Diagnostic procedure, 73, 99, 137 Diffusion, 137, 146

Index 169

Digestion, 13, 131, 132, 137, 146, 147, 161 Dilatation, 137, 155 Dilution, 50, 137, 151 Diploid, 137, 154 Direct, iii, 9, 20, 56, 101, 134, 137, 153, 157 Disease Transmission, 6, 18, 137, 138 Disease Transmission, Horizontal, 138 Disease Transmission, Vertical, 138 Disease Vectors, 5, 24, 138 Drive, ii, vi, 21, 63, 92, 138 Drug Interactions, 102, 138 Dura mater, 138, 149, 152 E Effector, 6, 134, 138 Efficacy, 11, 138 Electrolyte, 125, 138, 160 Electrons, 131, 138, 152 Electrophoresis, 8, 138 Emaciation, 127, 138 Embryo, 75, 133, 138, 140, 145 Empiric, 75, 138 Empirical, 55, 138 Emulsion, 138, 141 Encephalitis, 16, 26, 31, 32, 44, 47, 50, 52, 60, 80, 84, 90, 112, 139 Encephalitis Viruses, 26, 139 Encephalitis, Viral, 139 Encephalocele, 139, 151 Encephalomyelitis, 35, 139 Encephalopathy, 44, 139 Endemic, 16, 18, 19, 29, 44, 74, 75, 79, 125, 134, 139, 148 Endopeptidases, 139, 155 Endothelial cell, 26, 139, 162 Endotoxin, 139, 163 Enhancer, 8, 139 Environmental Exposure, 131, 139 Environmental Health, 40, 106, 108, 139 Enzymatic, 132, 135, 139, 154 Enzyme-Linked Immunosorbent Assay, 26, 28, 29, 30, 31, 38, 50, 64, 139 Eosinophils, 140, 143, 147 Epidemic, 18, 25, 29, 34, 35, 40, 41, 46, 48, 49, 51, 55, 58, 59, 74, 75, 96, 97, 98, 140 Epidemiologic Studies, 131, 140 Epidemiological, 14, 18, 19, 48, 49, 51, 140 Epithelial, 10, 140, 143 Epithelial Cells, 140, 143 Epithelium, 7, 140, 152 Epitope, 8, 9, 19, 30, 83, 140 Eukaryotic Cells, 140, 145, 152 Exhaustion, 140, 148

Exogenous, 13, 140 Extracellular, 140, 160, 161 Eye Infections, 127, 140 F Family Planning, 107, 140 Fatal Outcome, 140, 157 Febrile, 56, 60, 79, 80, 137, 140, 148, 149 Fetal Development, 140, 151 Fever of Unknown Origin, 48, 140 Fibrosis, 140 Filariasis, 5, 6, 24, 140 Fixation, 82, 141 Flavivirus, 15, 31, 76, 80, 81, 86, 137, 141, 165 Fold, 18, 141 Forearm, 132, 141 Fovea, 141 Fructose, 7, 141 G Gallbladder, 127, 134, 141 Gametogenesis, 24, 141 Gangrenous, 141, 159 Gastric, 59, 65, 141 Gastric Acid, 59, 65, 141 Gastrointestinal, 60, 141, 148, 159, 161, 163 Gelatin, 141, 142, 162 Gene, 5, 6, 7, 8, 9, 12, 14, 15, 18, 23, 24, 54, 76, 78, 82, 83, 90, 127, 128, 131, 141, 159 Gene Expression, 5, 8, 24, 141 Gene Silencing, 5, 15, 141 Generator, 11, 141 Genetic Code, 142, 152 Genetic testing, 142, 154 Genetics, 12, 19, 22, 24, 64, 142 Genomics, 9, 142 Genotype, 13, 18, 19, 79, 142, 153 Gland, 136, 142, 148, 149, 152, 155, 158, 161 Glomerular, 142, 157 Glucocorticoid, 78, 137, 142 Glucose, 133, 142 Glutamic Acid, 142 Glutamine, 7, 59, 65, 142 Glycine, 17, 142, 159 Glycogen, 22, 142 Glycoprotein, 77, 82, 84, 142, 162, 163 Glycosylation, 84, 142 Governing Board, 142, 155 Gp120, 28, 142 Grade, 7, 142 Graft, 143, 144 Granulocytes, 143, 160, 165

170 Dengue Fever

Growth, 5, 12, 15, 27, 129, 130, 131, 133, 137, 140, 143, 144, 146, 149, 151, 152, 154, 163 H Habitat, 17, 143 Haematoma, 40, 143 Haemoptysis, 40, 143 Haemorrhage, 32, 40, 143 Hantavirus, 19, 143 Haploid, 143, 154 Haplotypes, 9, 14, 44, 143 Headache, 74, 75, 79, 85, 102, 124, 143, 146 Headache Disorders, 143 Health Status, 143, 165 Hemocytes, 6, 143 Hemorrhage, 79, 136, 143, 156 Hepatitis, 22, 78, 89, 143, 164 Hepatocytes, 86, 143 Hepatoma, 86, 143 Heredity, 141, 142, 143 Herpes, 78, 143, 144 Herpes Zoster, 78, 144 Homologous, 15, 83, 128, 136, 144, 150, 159, 161 Homotypic, 87, 144 Hormonal, 144, 165 Hormone, 131, 136, 144, 159, 165 Horseradish Peroxidase, 139, 144 Human papillomavirus, 20, 144 Humoral, 4, 6, 7, 144 Humour, 144 Hybrid, 134, 144 Hybridization, 13, 81, 144 Hydrogen, 127, 131, 132, 137, 144, 150, 152 Hydrolysis, 144, 153, 154, 156 Hydrophilic, 22, 144 Hyperaemia, 135, 144 Hypertension, 143, 144 I Id, 66, 69, 113, 114, 120, 122, 144 Imidazole, 131, 144 Immune response, 4, 6, 8, 9, 10, 11, 16, 76, 81, 127, 129, 136, 144, 145, 148, 161, 164, 165 Immune Sera, 144, 145 Immune system, 4, 74, 75, 77, 84, 129, 144, 145, 148, 164, 165 Immunity, 4, 6, 7, 21, 50, 77, 79, 80, 83, 84, 87, 126, 127, 145, 163 Immunization, 84, 145 Immunoassay, 47, 139, 145 Immunodeficiency, 39, 78, 89, 127, 145

Immunogen, 81, 83, 145 Immunogenic, 27, 31, 74, 75, 84, 145 Immunoglobulin, 26, 27, 28, 29, 30, 31, 32, 38, 50, 129, 145, 150 Immunologic, 58, 133, 145 Immunology, 5, 17, 24, 25, 38, 53, 68, 127, 128, 144, 145 Immunosuppressive, 142, 145 In situ, 7, 23, 145 In Situ Hybridization, 7, 23, 145 In vitro, 4, 5, 10, 12, 86, 145, 154, 159, 162 In vivo, 4, 5, 10, 12, 14, 86, 145 Incubation, 16, 145 Indicative, 90, 145, 153, 164 Induction, 86, 145 Infarction, 136, 145, 149 Infiltration, 146, 155 Inflammation, 129, 134, 135, 137, 139, 140, 141, 143, 144, 146, 149, 152, 154, 158, 160, 164 Influenza, 16, 25, 48, 77, 78, 91, 146 Infusion, 64, 146, 163 Ingestion, 129, 146 Inhalation, 127, 146 Initiation, 8, 146 Inpatients, 19, 146 Insect Vectors, 5, 13, 146 Insect Viruses, 5, 146 Insight, 24, 146 Interferon, 29, 47, 146 Interferon-alpha, 146 Interstitial, 146, 149, 157 Intestinal, 146, 165 Intestine, 132, 144, 146, 161 Intracellular, 15, 145, 146, 149, 159, 165 Intracellular Membranes, 146, 149 Intravenous, 60, 64, 126, 146 Invasive, 145, 146 Invertebrates, 15, 138, 143, 146 Isoelectric, 146, 147, 161 Isoelectric Point, 147, 161 J Joint, 124, 130, 147 K Kb, 5, 8, 78, 80, 85, 106, 147 Keto, 147, 162 Kilobase, 80, 147 Kinetic, 23, 147 L Labile, 134, 147 Leptospira, 19, 147 Leptospirosis, 90, 147

Index 171

Lethal, 4, 10, 79, 82, 83, 147 Leukemia, 43, 147 Leukocytes, 53, 131, 132, 133, 140, 143, 146, 147, 150, 151, 163 Library Services, 120, 147 Life cycle, 22, 25, 131, 147 Linkage, 14, 16, 147 Lipid, 22, 82, 147 Lipoprotein, 147, 164 Liposome, 16, 147 Liver, 26, 33, 52, 53, 124, 127, 131, 136, 138, 141, 142, 143, 147, 165 Localized, 141, 143, 145, 147, 154 Locomotion, 147, 154 Lupus, 112, 147 Lymph, 133, 139, 144, 148, 158 Lymph node, 133, 148, 158 Lymphatic, 5, 6, 23, 146, 148, 158, 160, 162 Lymphatic system, 148, 158, 160, 162 Lymphocyte, 26, 30, 37, 53, 56, 127, 129, 148 Lymphocyte Count, 127, 148 Lymphocyte Subsets, 56, 148 Lymphocytic, 33, 148 Lymphoid, 129, 136, 148 Lymphokine, 14, 148 Lysosome, 9, 148 Lyssavirus, 148, 157 Lytic, 148, 159 M Major Histocompatibility Complex, 143, 148 Malaise, 79, 124, 148 Malaria, 5, 6, 7, 13, 21, 23, 24, 30, 53, 55, 58, 89, 93, 96, 112, 148, 149 Malaria, Falciparum, 148, 149 Malaria, Vivax, 148, 149 Malignant, 127, 149, 151 Mastitis, 149, 159 Measles Virus, 78, 149 Mediate, 13, 149 MEDLINE, 107, 149 Meiosis, 149, 150, 161 Membrane, 9, 16, 54, 77, 82, 84, 133, 135, 137, 140, 142, 149, 150, 152, 158, 160, 163 Membrane Fusion, 9, 16, 149 Meninges, 133, 136, 138, 149 Meningitis, 60, 112, 149 Mental Health, iv, 3, 106, 108, 149, 156 Metaphase, 23, 149, 161 MI, 57, 126, 149

Microbiology, 5, 11, 12, 15, 17, 24, 37, 49, 50, 64, 65, 68, 127, 130, 149 Microorganism, 134, 149, 153, 165 Microscopy, 16, 56, 144, 149 Migration, 17, 149 Mitochondrial Swelling, 149, 150 Mitosis, 130, 149 Mobility, 6, 8, 149 Molecular, 5, 7, 9, 11, 12, 13, 14, 15, 16, 17, 18, 20, 22, 23, 24, 54, 75, 107, 109, 131, 135, 149, 150, 163 Molecular Evolution, 18, 150 Molecule, 82, 129, 131, 135, 138, 140, 142, 144, 150, 152, 154, 157, 159, 162, 164 Monitor, 53, 150, 151 Monoclonal, 82, 83, 150 Monoclonal antibodies, 82, 150 Monocytes, 10, 14, 26, 147, 150 Mononuclear, 14, 28, 77, 150, 163 Morbillivirus, 149, 150 Morphological, 138, 150 Mosquito Control, 24, 150 Mucosa, 147, 150 Multivalent, 9, 150 Mumps Virus, 78, 150 Mung bean, 23, 150 Mutagenesis, 16, 26, 150 Mutagens, 150 Myalgia, 79, 124, 146, 150 Myocardium, 149, 150 N Nasal Mucosa, 146, 150 Necrosis, 47, 130, 140, 145, 149, 150 Need, 4, 21, 78, 87, 89, 92, 115, 127, 142, 148, 151, 162 Neoplasm, 151, 163 Nerve, 129, 137, 151, 152, 155, 161 Nervous System, 133, 151, 157, 161 Networks, 8, 151 Neural, 8, 55, 139, 144, 151 Neural tube defects, 55, 151 Neuroblastoma, 30, 86, 151 Neurologic, 60, 112, 139, 151 Neurologic Manifestations, 60, 151 Neurons, 86, 137, 151, 157, 161 Neutralization, 11, 30, 79, 82, 83, 151 Neutralization Tests, 82, 151 Neutrophils, 143, 144, 147, 151 Niacin, 151, 163 Nitrogen, 141, 142, 151, 163 Nuclear, 12, 138, 140, 150, 151 Nuclei, 138, 149, 151, 158

172 Dengue Fever

Nucleic acid, 16, 76, 132, 142, 144, 145, 150, 151, 152, 156, 165 Nucleic Acid Hybridization, 144, 152 Nucleocapsid, 82, 152 Nucleus, 130, 131, 134, 136, 140, 149, 150, 151, 152, 155, 161 O Odds Ratio, 152, 157 Oogenesis, 13, 152 Opacity, 137, 152 Ophthalmology, 141, 152 Opportunistic Infections, 127, 152 Organ Culture, 152, 162 Organelles, 136, 150, 152 Osteoporosis, 112, 152 Ovum, 147, 152 Oxidation, 24, 127, 130, 152 P Pachymeningitis, 149, 152 Palliative, 152, 161 Pancreas, 127, 131, 152, 163 Papillomavirus, 152 Parasite, 6, 23, 24, 153 Parasitic, 13, 24, 91, 112, 153 Parasitic Diseases, 24, 91, 112, 153 Particle, 82, 84, 147, 153, 162, 165 Pathogen, 6, 8, 13, 21, 145, 153 Pathogenesis, 14, 20, 27, 29, 65, 85, 153 Pathologic, 130, 136, 153 Pathologic Processes, 130, 153 Pathologies, 16, 153 Peptide, 8, 9, 16, 19, 23, 36, 77, 81, 139, 153, 154, 155, 156 Perennial, 153, 163 Peripheral blood, 9, 14, 19, 26, 53, 146, 153 Peritoneal, 130, 153 Peritoneal Cavity, 130, 153 Petechiae, 74, 75, 124, 143, 153 Phallic, 141, 153 Pharmacokinetic, 59, 65, 153 Pharmacologic, 129, 153, 162 Pharynx, 146, 153 Phenotype, 10, 131, 153 Phospholipases, 153, 159 Phosphorus, 132, 153, 154 Phosphorylation, 12, 153 Physiologic, 131, 140, 154, 157 Physiology, 5, 13, 64, 131, 154 Plague, 91, 154 Plants, 5, 15, 131, 132, 133, 142, 154, 158, 162, 163 Plaque, 30, 82, 83, 154

Plasma, 14, 27, 43, 64, 129, 133, 141, 154, 164 Plasma cells, 129, 154 Plasmid, 11, 76, 83, 154, 164 Platelet Activation, 154, 160 Polyarthritis, 16, 154 Polymerase, 33, 56, 80, 85, 154 Polymerase Chain Reaction, 33, 56, 80, 85, 154 Polymorphic, 19, 154 Polymorphism, 19, 154 Polypeptide, 128, 135, 144, 154, 156, 165 Polysaccharide, 129, 133, 154 Postmenopausal, 152, 155 Postsynaptic, 155, 159 Potentiation, 155, 160 Practice Guidelines, 108, 155 Preclinical, 7, 21, 155 Precursor, 12, 22, 54, 80, 84, 138, 139, 155, 163, 165 Prenatal, 138, 155 Prevalence, 13, 78, 152, 155 Probe, 78, 155 Procaine, 78, 155 Progression, 129, 155 Progressive, 133, 137, 143, 150, 154, 155, 157, 163 Projection, 136, 155 Promoter, 8, 13, 155 Prophase, 150, 155, 161 Prophylaxis, 155, 164 Proportional, 139, 155 Prostate, 131, 155, 163 Protease, 22, 155 Protease Inhibitors, 23, 155 Protein C, 17, 128, 130, 147, 156, 164 Protein Conformation, 17, 128, 156 Protein S, 8, 84, 90, 131, 135, 142, 156, 158 Proteolytic, 16, 134, 156 Protocol, 59, 65, 156 Protozoa, 149, 156, 163 Psychiatric, 131, 156 Psychiatry, 141, 156 Public Policy, 107, 156 Publishing, 25, 156 Pulmonary, 40, 132, 135, 156, 164 Pulmonary Artery, 132, 156, 164 Pulse, 10, 11, 124, 150, 156 Purines, 156, 159 Purpura, 143, 156 Pyridoxal, 156, 162

Index 173

Q Quaternary, 156, 157 R Rabies, 78, 148, 157 Rabies Virus, 78, 148, 157 Race, 149, 157 Radioactive, 144, 150, 151, 157 Radiopharmaceutical, 142, 157 Randomized, 64, 138, 157 Receptivity, 35, 157 Receptor, 15, 64, 127, 129, 142, 157, 159 Recombinant, 8, 12, 13, 21, 25, 28, 31, 32, 81, 82, 83, 84, 86, 157, 164 Recombinant Proteins, 8, 157 Recombination, 13, 18, 32, 157 Refer, 1, 132, 134, 141, 144, 147, 157 Refraction, 157, 160 Refractory, 12, 157 Regimen, 138, 157 Relative risk, 14, 157 Renal failure, 35, 157 Replicon, 12, 157 Reproductive cells, 141, 157 Respiration, 133, 150, 158 Retrospective, 34, 49, 158 Reverse Transcriptase Polymerase Chain Reaction, 56, 158 Rhinitis, 158, 159 Rhinovirus, 78, 158 Ribosome, 158, 163 Rickets, 158, 165 Rigidity, 154, 158 Risk factor, 55, 56, 140, 157, 158 Rubella, 56, 75, 158 Rubulavirus, 150, 158 S Saliva, 28, 157, 158 Salivary, 136, 158 Salivary glands, 136, 158 Saponin, 68, 158 Screening, 8, 28, 86, 89, 134, 158 Secretion, 84, 144, 158 Segmental, 36, 158 Segmentation, 158, 159 Segregation, 157, 159 Senile, 152, 159 Septicaemia, 159 Sequence Homology, 76, 159 Sequencing, 5, 15, 23, 154, 159 Serial Passage, 74, 75, 87, 159 Serine, 5, 22, 139, 159 Serologic, 49, 61, 145, 159

Serology, 14, 159 Serotonin, 159, 163 Serotypes, 4, 6, 8, 9, 11, 13, 15, 18, 19, 21, 31, 74, 75, 76, 79, 81, 83, 86, 137, 159 Serous, 130, 159 Serum, 28, 30, 38, 57, 80, 129, 130, 134, 144, 151, 159, 163 Shock, 4, 12, 16, 18, 22, 39, 40, 42, 54, 64, 74, 75, 76, 77, 79, 82, 83, 85, 87, 126, 159, 163 Side effect, 78, 101, 127, 159, 162 Signal Transduction, 25, 159 Signs and Symptoms, 151, 160 Sindbis Virus, 128, 160 Skull, 136, 139, 151, 160, 161 Smallpox, 160, 164 Sodium, 64, 78, 160 Somatic, 144, 149, 160 Specialist, 115, 160 Specificity, 16, 19, 30, 53, 128, 139, 160 Spectrum, 8, 37, 160 Sperm, 134, 157, 160 Spina bifida, 151, 160 Spinal cord, 133, 134, 138, 139, 149, 151, 152, 160 Spirochete, 160, 161 Spleen, 57, 136, 148, 160 Sputum, 143, 160 Steroids, 136, 142, 160 Stimulus, 138, 161 Stomach, 127, 141, 144, 153, 160, 161 Strand, 12, 76, 84, 154, 161 Streptavidin, 64, 161 Streptococci, 20, 161 Stress, 86, 161 Subacute, 145, 161 Subarachnoid, 143, 161 Subclinical, 50, 145, 161 Subspecies, 160, 161, 164, 165 Substance P, 158, 161 Substrate, 139, 161 Suppression, 141, 161 Synaptic, 160, 161 Synergistic, 18, 26, 161 Syphilis, 89, 161 Systemic, 102, 132, 146, 161, 163, 164, 165 T Temporal, 18, 143, 161 Tetravalent, 4, 7, 8, 9, 11, 27, 161 Therapeutics, 102, 161 Thermal, 154, 161 Threonine, 159, 162

174 Dengue Fever

Thrombin, 156, 162 Thrombocytopenia, 45, 46, 64, 162 Thrombomodulin, 156, 162 Thrombosis, 156, 162 Thymus, 145, 148, 162 Ticks, 141, 162 Tissue Culture, 16, 27, 29, 151, 162 Tolerance, 127, 162 Tooth Preparation, 127, 162 Tourniquet, 74, 75, 125, 162 Toxic, iv, 24, 139, 145, 162 Toxicity, 138, 162 Toxicology, 21, 108, 162 Toxins, 129, 131, 139, 145, 150, 162 Transaminase, 24, 57, 162 Transcriptase, 28, 32, 80, 85, 162 Transduction, 159, 162 Transfection, 9, 131, 162 Transfer Factor, 145, 163 Transferases, 142, 163 Transfusion, 55, 89, 163 Translation, 7, 22, 163 Translational, 141, 163 Transplantation, 145, 148, 163 Transposons, 6, 163 Trauma, 150, 163 Trees, 18, 163 Trophic, 25, 163 Trypanosomiasis, 89, 163 Tryptophan, 24, 159, 163 Tsetse Flies, 5, 163 Tuberculosis, 135, 147, 163 Tumor marker, 131, 163 Tumor Necrosis Factor, 47, 64, 163 Tumour, 47, 163 Typhoid fever, 91, 163 U Unconscious, 136, 144, 164 Uremia, 157, 164 V Vaccination, 4, 11, 28, 81, 83, 86, 164 Vaccinia, 11, 12, 86, 164

Vaccinia Virus, 12, 86, 164 Variola, 91, 164 Vascular, 143, 145, 146, 164 Vasculitis, 33, 164 Vein, 146, 151, 164 Venereal, 161, 164, 165 Venous, 156, 164 Ventricle, 156, 164 Venules, 132, 164 Vesicular, 144, 160, 164 Veterinary Medicine, 107, 164 Viraemia, 56, 164 Viral Hepatitis, 89, 164 Viral vector, 5, 164 Viremia, 10, 11, 27, 81, 164 Virion, 12, 25, 77, 80, 84, 152, 164 Virulence, 10, 18, 75, 130, 159, 162, 165 Virus Replication, 10, 15, 28, 32, 165 Visceral, 42, 165 Vitamin D, 64, 158, 165 Vitro, 5, 12, 165 Vivo, 4, 5, 9, 12, 15, 19, 165 W War, 93, 98, 143, 165 Warts, 144, 165 White blood cell, 129, 147, 148, 154, 165 World Health, 36, 47, 82, 89, 91, 113, 126, 165 X Xenograft, 129, 165 X-ray, 125, 151, 165 Y Yaws, 89, 165 Yeasts, 153, 165 Yellow Fever, 7, 13, 17, 19, 24, 26, 27, 31, 32, 50, 79, 84, 90, 91, 93, 127, 141, 165 Yellow Fever Vaccine, 50, 165 Yellow Fever Virus, 19, 31, 32, 80, 84, 141, 165 Z Zoonoses, 157, 165 Zymogen, 156, 165

Index 175

176 Dengue Fever

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Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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