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

SYPHILIS 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 2004 by ICON Group International, Inc. Copyright 2004 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., 1960Syphilis: 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: 0-597-84083-0 1. Syphilis-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 syphilis. 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 SYPHILIS .................................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Syphilis ......................................................................................... 5 E-Journals: PubMed Central ....................................................................................................... 31 The National Library of Medicine: PubMed ................................................................................ 35 CHAPTER 2. NUTRITION AND SYPHILIS .......................................................................................... 79 Overview...................................................................................................................................... 79 Finding Nutrition Studies on Syphilis ........................................................................................ 79 Federal Resources on Nutrition ................................................................................................... 81 Additional Web Resources ........................................................................................................... 81 CHAPTER 3. ALTERNATIVE MEDICINE AND SYPHILIS .................................................................... 83 Overview...................................................................................................................................... 83 National Center for Complementary and Alternative Medicine.................................................. 83 Additional Web Resources ........................................................................................................... 85 General References ....................................................................................................................... 88 CHAPTER 4. DISSERTATIONS ON SYPHILIS ...................................................................................... 89 Overview...................................................................................................................................... 89 Dissertations on Syphilis ............................................................................................................. 89 Keeping Current .......................................................................................................................... 90 CHAPTER 5. CLINICAL TRIALS AND SYPHILIS................................................................................. 91 Overview...................................................................................................................................... 91 Recent Trials on Syphilis ............................................................................................................. 91 Keeping Current on Clinical Trials ............................................................................................. 92 CHAPTER 6. PATENTS ON SYPHILIS ................................................................................................. 95 Overview...................................................................................................................................... 95 Patents on Syphilis ...................................................................................................................... 95 Patent Applications on Syphilis................................................................................................. 111 Keeping Current ........................................................................................................................ 112 CHAPTER 7. BOOKS ON SYPHILIS .................................................................................................. 113 Overview.................................................................................................................................... 113 Book Summaries: Federal Agencies............................................................................................ 113 Book Summaries: Online Booksellers......................................................................................... 115 The National Library of Medicine Book Index ........................................................................... 118 Chapters on Syphilis .................................................................................................................. 119 CHAPTER 8. MULTIMEDIA ON SYPHILIS........................................................................................ 121 Overview.................................................................................................................................... 121 Video Recordings ....................................................................................................................... 121 Audio Recordings....................................................................................................................... 122 Bibliography: Multimedia on Syphilis ....................................................................................... 123 CHAPTER 9. PERIODICALS AND NEWS ON SYPHILIS..................................................................... 125 Overview.................................................................................................................................... 125 News Services and Press Releases.............................................................................................. 125 Newsletter Articles .................................................................................................................... 129 Academic Periodicals covering Syphilis..................................................................................... 130 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 131 Overview.................................................................................................................................... 131 U.S. Pharmacopeia..................................................................................................................... 131 Commercial Databases ............................................................................................................... 132 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 137

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Overview.................................................................................................................................... 137 NIH Guidelines.......................................................................................................................... 137 NIH Databases........................................................................................................................... 139 Other Commercial Databases..................................................................................................... 143 APPENDIX B. PATIENT RESOURCES ............................................................................................... 145 Overview.................................................................................................................................... 145 Patient Guideline Sources.......................................................................................................... 145 Finding Associations.................................................................................................................. 153 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 155 Overview.................................................................................................................................... 155 Preparation................................................................................................................................. 155 Finding a Local Medical Library................................................................................................ 155 Medical Libraries in the U.S. and Canada ................................................................................. 155 ONLINE GLOSSARIES................................................................................................................ 161 Online Dictionary Directories ................................................................................................... 166 SYPHILIS DICTIONARY............................................................................................................. 167 INDEX .............................................................................................................................................. 221

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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 syphilis 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 syphilis, 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 syphilis, 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 syphilis. 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 syphilis, 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 syphilis. The Editors

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

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

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and syphilis, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in 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 “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “syphilis” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Otosyphilis in a Patient with Human Immunodeficiency Virus: Internal Auditory Canal Gumma Source: Otolaryngology: Head and Neck Surgery. 112(3): 488-492. March 1995. Summary: This article presents a case report of a patient with progressive bilateral (both sides) sensorineural hearing loss (SNHL) and new onset dysequilibrium (loss of balance). A 42-year-old man presented after he had subjective hearing loss and tinnitus with intermittent disequilibrium. At his initial visit, audiometric examination revealed moderately severe sensorineural hearing loss in the high frequencies of the left ear and a mild to moderate, mixed hearing loss in the right ear. Magnetic resonance imaging (MRI) revealed a left internal auditory canal (IAC) mass lesion, and he was initially thought to have an acoustic schwannoma. However, on further evaluation, he was found to be infected with syphilis and HIV. The authors diagnosed the patient with

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Syphilis

otosyphilis with a left IAC gumma. Surgery was canceled because of the high probability of infectious involvement. The patient was given a 3-week course of benzathine penicillin G, 2.4 million units per week by intramuscular injection, and began taking azidothymidine (AZT). After six weeks, the patient had significant improvement in hearing bilaterally. The most recent audiogram, obtained approximately six months after diagnosis and four months after treatment, was entirely within normal limits. Despite developing AIDS and later dying of HIV encephalopathy, the patient had no subsequent auditory or vestibular symptoms or sequelae. 2 figures. 23 references. (AA-M). •

Prevalence of Syphilis, Hepatitis B Virus (HBV), and Human Immunodeficiency Virus (HIV) Infection in New Arrestees at the Lake County Jail, Crown Point, Indiana Source: Journal of Prison & Jail Health; Vol. 12, no. 2, Winter 1993. Contact: Eli Lilly and Company, Eli Lilly Corporate Center, Indianapolis, IN, 46285, (317) 276-2000, http://www.lilly.com. Summary: This article reviews a study conducted to determine the prevalence in arrestees of syphilis, hepatitis B virus (HBV), and HIV infection by demographic and behavioral characteristics, and to evaluate the costs associated with universal screening for these sexually transmitted diseases compared with a theoretical targeted screening program. Three hundred and nineteen arrestees were screened for syphilis, HBV, and anonymously for HIV infection. The prevalence of syphilis was 2.5 percent; hepatitis B surface antigen prevalence was 1.6 percent; the prevalence of past or present HBV infection was 21.9 percent; and the prevalence of HIV infection was 1.6 percent. Targeted screening for sexually transmitted diseases was found to be more costeffective.

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Retrospective Study of Syphilis Seropositivity in a Cohort of Demented Patients Source: Alzheimer Disease and Associated Disorders. 7(1): 33-38. Spring 1993. Summary: This journal article describes a retrospective study that examined the rate of syphilis seropositivity in a sample of 376 patients with dementia. The mean age was 74 years and 73 percent were women. All patients had received medical, psychosocial, psychological, psychiatric, neurological, and laboratory evaluations. Diagnoses included Alzheimer's disease in 30 percent of the sample, vascular dementia in 25 percent, combined Alzheimer's disease and vascular dementia in 14 percent, and other diagnoses in 31 percent. The mean Mini Mental State Examination score was 16, indicating moderately advanced dementia. Fluorescent treponemal antibody absorption tests (FA), used to diagnose neurosyphilis, were performed in 338 of the patients and were reactive in 10.9 percent. Nine patients received both FA and rapid plasma reagin (RPR) tests. All had positive FA tests but only 2 had reactive RPR tests. 15 references.

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The Resurgence of Syphilis in the United States Source: Current Opinion in Infectious Diseases, 1991; Vol. 4. Contact: US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Center for Prevention Services, Division of Sexually Transmitted Disease, 1600 Clifton Rd NE, Atlanta, GA, 30333, (404) 639-8002. Summary: This reprint of a journal article says that more cases of both primary and secondary syphilis were reported in 1989 than in any other year since 1949, and that the amount of infection is on the rise in spite of four decades of penicillin therapy. The

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Studies

rising incidence of drug use has been linked to the spread of the Sexually transmitted disease (STD). The article says that observations in patients coinfected with Human immunodeficiency virus (HIV) have raised questions about the adequacy of penicillin treatment. Efforts to control the epidemic have brought needed attention to improving health care delivery to persons at risk for syphilis. It examines the epidemiology of early syphilis infection, congenital syphilis, interventions, treatment, and the connection between syphilis and HIV.

Federally Funded Research on Syphilis The U.S. Government supports a variety of research studies relating to syphilis. 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 syphilis. 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 syphilis. The following is typical of the type of information found when searching the CRISP database for syphilis: •

Project Title: ADOLESCENTS TRANSMISSION

IN

THE

DRUG

CULTURE

AND

STD

Principal Investigator & Institution: Rothenberg, Richard B.; Professor; Family and Preventive Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-AUG-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AIDS INTERNATIONAL TRAINING AND RESEARCH PROGRAM Principal Investigator & Institution: Johnson, Warren D.; Chief and Professor; Medicine; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 21-SEP-1998; Project End 31-MAY-2003 Summary: The objective of this proposal is to build on previous successful collaborations between (Cornell) researchers from Weill Medical College of Cornell University (formerly known as Cornell University Medical College), the Haitian Study Group on Kaposi's Sarcoma and Opportunistic Infections (GHESKIO), the Haitian Red Cross, and the Haitian Ministry of Health to develop a national blood safety program for Haiti, which may serve as a model for blood safety programs in other developing countries. Studies by Cornell-GHESKIO researchers in 1983, during the early stages of

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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Syphilis

the HIV epidemic in Haiti, demonstrated that 40% of the HIV infected women in Portau-Prince had received a blood transfusion. Cornell-GHESKIO researchers identified a for-profit blood bank as a source of many of these transfusions. Based upon this information, the Haitian Ministry of Health closed the for-profit blood bank in 1986, and placed the Haitian Red Cross in charge of blood safety in Haiti. In 1988, with the assistance of a Fogarty training grant, Cornell-GHESKIO researchers trained the administration and technical staff of the Haitian Red Cross in blood safety testing. The Haitian Red Cross, with on-going technical advice from Cornell-GHESKIO researchers, continues to monitor blood safety in Port-au-Prince. The current proposal aims to solidify the training of the Haitian Red Cross in Port-au-Prince and to expand their activities to rural Haiti where 70% of the population lives. The highest priority will be given to the training of personnel directly involved in blood banking operations (laboratory technicians, counselors and data entry staff), as well as physicians who are most likely to use blood products (obstetricians and surgeons). In addition, the general public will be educated and encouraged to give regular blood donations and to avoid paid donors. The current proposal also aims to address several areas of research of importance for blood safety in Haiti: 1) determine the prevalence rate and risk factors for infection with blood borne pathogens among blood donors in urban and rural Haiti including HIV-1, HIV-2, HTLV-1, HCV, HBV, syphilis, and malaria; 2) determine the prevalence and risk factors among blood donors of HIV-infected individuals in the "window period", the time between HIV infection and development of HIV antibodies detectable by standard ELISA assays. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AN EDUCATIONAL INTERVENTION FOR OLDER CRACK USERS Principal Investigator & Institution: Johnson, Wendell A.; Family and Preventive Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant): This proposed planning initiative is designed to: 1) increase our understanding and knowledge of HIV risks factors which are specific to middle-aged and older African American male and female users of crack cocaine, and; 2) demonstrate the effectiveness of an age- specific outreach intervention designed to gain access to target group members, increase AIDS knowledge and health risk (e.g. HIV; STD) awareness, assist clients in assessing individual health risk, and promote drug free living. Utilizing a pre-post test intervention design, we will recruit and collect baseline data on three groups of persons: (1) middle aged and older sexually active men (aged >50) for whom crack cocaine is the primary drug of choice (n=40); (2) middle aged and older sexually active women (aged >50) for whom crack cocaine is the primary drug of choice (n=40), and; (3) sexual partners; individuals who have engaged in a sexual act with members in groups 1 or 2 (n=80). Serologic testing for HIV and syphilis, and urine or vaginal swab for testing gonorrhea and chlamydia will be conducted on all study participants. We will conduct one post intervention assessment (including biologic test) in month 9 with Groups 1 and 2 only. These data will be used to describe and compare demographic, serologic, and HIV risk characteristics of older crack cocaine users and their sexual partners; measure and evaluate intervention impact and exposure. In parallel with these quantitative assessments, the qualitative, ethnographic component will consistent of ongoing direct observation augmented by 2 ethnographic interviews per week during the first year of the study and subsequent diminution to 1 interview per week until the conclusion of the study or until redundancy is reached. The ethnographic interviews will be held with selected study participants, their contacts,

Studies

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and other key informants (e.g. landlords, shopkeepers, persons involved in drugs in these neighborhoods, etc.). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL ASPECTS OF VIRUS-HARBORING TRICHOMONAS VAGINALIS Principal Investigator & Institution: Piper, Jeanna M.; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2001 Summary: Human suffering and health care costs due to sequellae of STDs are escalating worldwide, including pelvic inflammatory disease, chronic pelvic pain, involuntarily infertility, and ectopic pregnancies. Project 5 will correlate clinical characteristics of T. vaginalis infections (including behavioral and demographic features as well as co-infections with other STD agents) with the presence or absence of dsRNA virus in T. vaginalis isolates. These two clinical T. vaginalis isolate types (i.e., with and without dsRNA virus) exist naturally and contribute to different outcomes in clinical demographic, and behavior parameters to be evaluated. Thus, as documented in Project 1, the virus provides a marker from which to carry out comparative clinical and adverse outcome studies. Specific Aim 1 perform a comprehensive evaluation of T. vaginalis isolates with an without dsRNA virus and relate these data to various clinical parameters by a) examining characteristics (genitourinary symptoms and physical findings) between vaginitis caused by virus-harboring and virus-minus isolates in pregnant and non-pregnant women, b) evaluating behaviors, demographic features and partner history associated with the two isolate types of T. vaginalis, and c) establishing linkages between infection with the two isolate types and other STD agents. Specific Aim 2 will evaluate the risk of adverse outcomes in women with STDs during pregnancy by a) examining infections by T. vaginalis with and without dsRNA virus and b) simultaneously examining and identifying other current infections (gonorrhea, chlamydia, bacterial vaginosis, group B, streptococcus, syphilis, HHV8, and M. genitalium). Specific Aim 3 will facilitate collaborations with the other four Projects by a) providing fresh clinical T. vaginalis isolates from patients with trichomonosis for Project #1, b) coordinating identification and follow-up of pregnant women with the HHV8 Project #2 by collecting maternal samples and pregnancy outcome data, c) providing clinical data dn specimens for the Mycoplasma genitalium Project 3, and d) providing clinical expertise and additional infection information to Behavioral Project 4. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CUTANEOUS IMMUNE RESPONSE IN EARLY SYPHILIS Principal Investigator & Institution: Radolf, Justin D.; Director/ Professor; Ctr for Microbial Pathogenesis; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806 Timing: Fiscal Year 2001; Project Start 01-APR-1996; Project End 31-MAY-2006 Summary: (Applicant's Abstract): Venereal syphilis is a chronic inflammatory disorder driven by the persistence of its etiologic agent Treponema pallidum. Research in this proposal is based on the premise that the local (i.e., tissue-based) cellular immune responses to T. pallidum have two distinct, yet interrelated, consequences of fundamental importance to syphilis pathogenesis. They cause the tissue damage which ultimately gives rise to clinical manifestations, and they are primarily responsible for the clearance of bacteria, a prerequisite for lesion resolution. Human skin is the primary

8

Syphilis

focus of our efforts to elucidate these processes because (a) it is the major target organ of early syphilitic infection, (b) it is easily accessible to in vivo experimentation, and (c) there exists a wealth of reagents and information concerning its immune-related functions. During the prior funding interval, we have made considerable progress in characterizing the cellular infiltrates in secondary syphilis lesions and in delineating the ontogeny of the cutaneous response engendered by the syphilis spirochete. A unifying theme of this work has been the acquisition of considerable evidence, using a combination of in vitro and in vivo approaches, to support our primary hypothesis that the proinflammatory properties of treponemal lipoproteins are the primary triggers of innate immune mechanisms in early syphilis. More recently, we have shown that by recruiting a cellular infiltrate rich in antigen presenting cells, particularly dendritic cells, and memory/effector T cells, the innate immune processes induced by these lipidmodified polypeptides set the stage for the adaptive (i.e., specific) immune responses to the bacterium. One important outcome of these findings is the recognition that the cutaneous responses under investigation relate to primary as well as to secondary syphilis. In this competitive renewal application, we will extend this conceptual framework by further characterizing the in vivo biological responses to treponemal lipoproteins/lipopeptides (Aim One); by further characterizing the cutaneous immune response to T pallidum in secondary syphilis lesions (Aim Two); by using in vitro/ex vivo approaches to examine dendritic and T cell responses to T pallidum and treponemal proteins (Aim Three); and by examining our hypothesis that treponemal lipoproteins activate macrophages following uptake and degradation within the phagosomal vacuoles of macrophages (Aim Four). This work will result in an enhanced appreciation of the role of local cellular responses in syphilis pathogenesis and will provide a necessary underpinning for the eventual development of a safe and effective syphilis vaccine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DENDRITIC CELLS IN THE IMMUNOPATHOGENESIS OF SYPHILIS Principal Investigator & Institution: Norgard, M V.; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2001; Project Start 01-JUN-1997; Project End 31-MAY-2006 Summary: Syphilis, a chronic, complex sexually transmitted disease of humans caused by the spirochetal bacterium Treponema pallidum, remains a global public health problems. Although the immunology of syphilis is complex, clinical manifestations in all stages of syphilis derive principally from cell-mediated processes that are "triggered" by T. pallidum as it invades and replicates with genital skin. The actual cell type than initiates this early immune response thus far has not been identified. Over the past decade, overwhelming evidence suggests that dendritic cells (DCs) (e.g. Langerhans cells [LCs] of the epidermis and dermal dendritic cells [DDCs] are crucial for the initiation of primary T cell responses to foreign antigens. The working hypothesis for this second-year continuation application is that DCS likely serve as the pivotal immune effector cells that initiate the cellular inflammatory response during syphilis. Thus far, DCs in the cellular immune responses to T. pallidum have not been studied. Accordingly, the Specific Aims of this project have been (1) to characterize the interaction(s) of virulent T. pallidum with DCs, with emphasis on examining phagocytic processes, (2) To assess DC activation and/or maturation following exposure of immature DCs to T. pallidum or its constituent pro-inflammatory membrane lipoproteins, and (3) To examine whether tissue migration is induced following

Studies

9

exposure of DCs to T. pallidum or its membrane lipoproteins (longer range goal). Much progress already has been made over the last eight months towards accomplishing Specific Aims 1 and 2, utilizing two immortalized murine DC lines, XS52 and XS 106, developed and provided by Dr. Akira Takashima of the U.T. Southwestern Skin Disease Research Center. In Specific Aim 3; we will employ human skin organ cultures to examine T. pallidum- or lipoprotein-induced DC migration and activation. This study is likely to yield important new insights into the role(s) of DCS as key effector cells in the immunopathogenesis of syphilis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DOUCHING AND REPRODUCTIVE TRACT INFECTIONS Principal Investigator & Institution: Funkhouser, Ellen M.; Epidemiology & Interntl Health; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2004 Summary: Douching is a common practice among American women, especially in the South, among Black women, and among women who are less educated. Douching has been associated with many adverse health events including pelvic inflammatory disease and ectopic pregnancy, and to a much less well established degree, sexually transmitted diseases (STDs). The proposed project is a cross-sectional study of reproductive tract infections and douching practices in Jefferson County, AL. Women attending the County STD clinic and 2 County Family Planning Clinics will be interviewed prior to examination regarding douching practices and history of sexual activities, pregnancies, contraceptive practices, and STDs. Presence of infections and pH of vaginal secretions will be ascertained from appropriate tests. Cases will be women presenting with syphilis, gonorrhea, trichomonas, chlamydia , or bacterial vaginosis. Over a 29 month period 4,370 women, 1,400 from the STD clinic and 2,970 from the Family Planning Clinics, will be interviewed. This should provide about 935 STD cases, 577 cases of bacterial vaginosis without an STD, and 2,858 women with no infections. Douching practices among women with and without a reproductive tract infections will be compared. Logistic regression analysis will be used to assess the following: 1) whether douching is associated with increased risks of STDs or bacterial vaginosis; 2) whether douching is associated with vaginal pH; 3) whether there is a dose-response relationship regarding frequency of douching; and 4) whether the risk differs according to preparation used. We believe the similarities in socioeconomic status of women attending the clinics will be substantial making douching practices potentially one of the most distinguishing characteristics of women with and without an infection. Furthermore, the findings will be readily generalizable to a population that historically and currently has some of the highest STD rates in the nation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DRUG COUNSELING

ABUSE,

DEPRESSION

AND

RESPONSES

TO

HIV

Principal Investigator & Institution: Marmor, Michael; Environmental Medicine; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2005 Summary: (provided by applicant) The long-term objective of this research is to reduce the incidence of infection with human immunodeficiency virus type 1 (HIV) in industrialized countries by developing methods to identify and treat high-risk individuals whose response to HIV testing and counseling is hindered by

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Syphilis

psychopathology. The project's specific aims are (1) to describe the distribution of psychopathologies among persons undergoing HIV testing and counseling, and (2) to test the hypotheses that high-risk, HIV-seronegative persons with mild-to-moderate depression will be more likely to adopt protective behavior changes when provided with pharmacotherapy for their depression than when treated with placebo. The study design to achieve specific aim 2 will be a randomized, double-blinded clinical trial of bupropion hydrochloride versus placebo administered for a total of 7 months. The study population will be initially high-risk, HIV-seronegative men who have sex with men (MSM). Individuals who are ineligible or decline entry into the clinical trial will be entered into an observational study. The primary outcome measure of the clinical trial will be self-reported numbers of partners in unprotected receptive anal intercourse. Secondary outcomes will be substances used and frequency of substance use by selfreport and toxicology; (c) new infections with sexually transmitted infections including gonorrhea, syphilis, Kaposi's sarcoma-associated herpesvirus, and hepatitis C virus (HCV) and HIV; and (d) measures of psychological factors that have been shown to be, or are thought to be, associated with HIV incidence rates, including measures of selfefficacy, self-esteem, stage of change, and depression. Enrollment data from the observational study will be combined with enrollment data from the clinical trial to provide a description of the distribution of psychopathologies and substance abuse among high-risk MSM. Longitudinal data form the observational study will be used to assess the associations of psychopathologies, substances used and frequency of substance use with adverse outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ECONOMIC IMPACT OF HIV PREVENTION ON STDS Principal Investigator & Institution: Johnson-Masotti, Ana P.; Assistant Professor; Psychiatry and Behavioral Med; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2003 Summary: Sexual risk reduction interventions to prevent the transmission of HIV also have beneficial effects on other social health concerns, such as non-HIV STDS and unintended pregnancy. Most prior studies of the cost-effectiveness of HIV prevention interventions focus only on the impact of the intervention on HIV outcomes. Studies that neglect the impact of these interventions on other STDs and unintended pregnancies may underestimate the economic benefits of sexual behavior change. Furthermore, little is known regarding the cost-effectiveness of HIV prevention interventions viewed as STD (or unintended pregnancy) prevention programs. This application seeks funding to conduct a cost-effectiveness analysis of a community-level sexual behavior risk reduction intervention that was implemented at multiple locations in the U.S. The intervention targets low-income, predominantly African- American adolescents living in urban housing developments. This analysis will allow us to: 1) estimate the number of HIV and STD infections and the number of unintended pregnancies prevented by the intervention, as well as associated savings in medical care costs and lost economic productivity; 2) evaluate the cost-effectiveness of the intervention with regard to HIV (measured by the cost per HIV case averted), STDs (measured by the cost per chlamydia, gonorrhea, syphilis, HPV, or HBV case averted), and unintended pregnancies (measured by the cost per unintended pregnancy prevented); 3) compare the cost-effectiveness of this intervention with other HIV, STD, and unintended pregnancy prevention interventions; and 4) determine how much difference the addition of non-HIV STDs and unintended pregnancy outcomes make to

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the estimated HIV prevention cost-effectiveness of the intervention. The proposed, more inclusive, approach to estimating the cost-effectiveness of HIV prevention should produce more accurate estimate for use in policy analyses and resource allocation decision-making. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EMPOWERING WOMEN DRUG USERS TO REDUCE HIV RISK Principal Investigator & Institution: Gollub, Erica L.; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 20-JUN-2001; Project End 31-MAY-2004 Summary: (provided by applicant): Despite more than 15 years of behavioral intervention research seeking to reduce HIV risk behaviors among drug-using persons, drug-using women, across drug categories, remain at very high risk of HIV infection through unsafe sex. Available epidemiological data suggest that women drug users are at the highest risk of HIV infection relative to other risk groups in the US. State-of-theart HIV counseling and testing (CT) prevention approaches are insufficient to address women's risk. The proposed project uses a woman-specific prevention approach, already tested for feasibility and short-term behavior change on diverse cultural groups. The intervention (BESTBET) seeks to respond to the public health emergency among drug-using women by addressing the concrete realities of economic and emotional dependence on an often-risky sex partner, which provide the foundation of women's HIV risk. Based on Body Empowerment Theory, the proposed intervention provides interactive, skills-based learning, and offers a range of new protection technologies to women, including the female condom. Guided by an Advisory Board of national experts on drug-using women, and sexual behavior, the study seeks to empower women by creating a sense of control over one's body and health, increased community and peer support for new norms, and greater usage of healthful community resources (drug -related, medical, social). Group intervention sessions lead by trained "near-peer" counselors will focus on risk-reduction for sexual and drug-related HIV risk, and on combined drug-sex risk behavior. This 3-year, randomized controlled trial will recruit 240 out-of-treatment drug-using women in West Philadelphia. Both arms will first receive an enhanced HIV CT module composed of 2 short individualized counseling sessions. The study will test the effects of adding a multiple-group session model administered over 5 weeks, with 2 boosters, in the form of 'reunion sessions," against a control condition receiving only the CT module. Follow-up assessments for behavioral outcomes (via audio-assisted computer interview) and biological/serological outcomes (incidence of gonorrhea, Chlamydia and Trichomonas, HIV and syphilis) will occur at 6month intervals over 12 months. Treatment of incident infections will provide for valid measures of STD incidence. A strong relationship with community organizations will be sought, including: community input into the study throughout, training of community group leaders in study techniques and technologies, the distribution of women's "sexual risk reduction kits," and adoption of study activities by community groups by the time of study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPIDEMIOLOGY Principal Investigator & Institution: Zheng, Xiwen; Natl Ctr for Aids Prevention and Control Prevention and Control (Ncaids) Beijing, Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2006

12

Syphilis

Summary: The purpose of the Epidemiology Project (Project 1) is to establish HIV incidence and risk factors for HIV infection in three regions of China in order to establish a foundation for conducting clinical trials of HIV prevention and therapeutic interventions. The three specific aims of Project 1 are: Aim 1: To estimate the prevalence and incidence of HIV-1 infection and selected sexually transmitted diseases over time in: a) former plasma donors (FPDs), their stable sexual partners, and their children in rural areas of Shanxi province; b) injection drug users (IDUs) and their stable sexual partners in rural areas of Yunnan Province; and c) female sex workers (FSWs) in Kunming, Yunnan Province; Aim 2: To determine risk factors for HIV infection in the above population, and to recruit participants from these populations for participation in cohort studies in preparation for vaccine, behavioral and therapeutic intervention studies; and Aim 3: TO estimate the prevalence and incidence of HIV-1 infection, HHV8 infection and co-infection with HIV-1 and HHV8 in high risk minority population in Xinjiang Province, and to determine factors that are independently associated with co- infection with HIV-1 and HHV8. Strategies for recruitment and retention of study subjects will vary by study populations. About 1680 FPDs and 900 spouses will be recruited from 12 villages in Shanxi. About 600 HIV-FPDs or HIV-spouses will be followed in year 3 and 5. About 960 IDUs and 400 spouses will be recruited from 48 villages in Yunnan. About 504 HIV-IDUs and some 250 HIV-spouse will be followed at 6, 12, 18, 24 and 30 months after baseline. About 1000 FSWs will be recruited in hotels, entertainment establishments, and in the streets of Kunming City, Yunnan. FSWs will e followed for 2 years with 3 months interval contract and 6-month interval for assessment. About 250 subjects each will be recruited from Kelkez, Kazak, Ughur and Han ethnic groups and followed annually in Urumi, Xinjiang Four biologic indicators (HIV, gonorrhea, chlamydia, and syphilis) will be used cross all 4 study populations. HHV8 will be additionally used in study of minorities in Xinjiang. Our FPD and IDU studies will provide a subject of subjects (HIV positive) for the behavioral intervention study planned in Project 2. In collaboration with Project 4, we will seek to provide clinical care for HIV infected persons identified over the course of recruitment. We will provide clinical specimens for key research initiatives described in Projects 3 and 4. Planning for field trials or candidate HIV vaccines will link Projects 1 and 5. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXPRESSION AND FUNCTION OF MSP HOMOLOGUES IN T PALLIDUM Principal Investigator & Institution: Centurion-Lara, Arturo; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001 Summary: As primary syphilis resolves, most treponemes are cleared from the chancre. However, a few organisms escape the immune response to cause secondary syphilis and ultimately to establish chronic infection. May theories have been proposed to explain Treponema pallidum's capacity for immune evasion, yet none has convincing experimental support. Antigen variation is one of the most intriguing theories, but not candidate antigens have been identified until now. The recent identification of a polymorphic multicopy gene family in T. pallidum that encodes for proteins with predicated amino acid homology to the major sheath protein (msp) of Treponema denticola provides a family of likely candidates. We call these T. pallidum proteins the msp-homologues. The broad goal of this proposal is to determine the cellular location and the function of the msp-homologue proteins. The specific aims of the project are the following: 1. Determine whether msp-homologues are surface exposed antigens in T.

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pallidum Nichols strain. This aim will test the hypothesis that some of the msphomologues are surface exposed in living organisms. 2. Determine whether msphomologues are involved in cell attachment and function as porins. This aim will determine whether the msp-homologue family has a role in two well-recognized mechanisms of pathogenesis of bacterial infections. 3. Determine whether T. pallidum Nichols strain represents a colonal bacterial population or is comprised of subpopulations of treponemes. This aim will test the hypothesis that, like other spirochetes, T. pallidum strains contain subpopulations that express heterogeneous msp- homologues. 4. Determine whether the msp-homologues undergo antigen variation or phase variation. Antigenic variation is common other pathogenic treponemes and the msp-homologue gene family has characteristics highly suggestive of genetic recombination and reassortment. This aim will test the hypothesis that individual msp-homologues either change (antigenic variation) or are no longer expressed (phase variation) during the course of infection. The studies proposed in this application will define the role of the msp- homologues in immune evasion and in the pathogenesis of syphilis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PALLIDUM

EXTRACELLULAR

MATRIX

ADHESINS

OF

TREPONEMA

Principal Investigator & Institution: Cameron, Caroline E.; Assistant Professor; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2006 Summary: (Provided by the applicant): Syphilis, caused by the spirochete bacterium Treponema pallidum subsp. pallidum, is a chronic bacterial infection that remains a public health concern worldwide, with an estimated 12 million new cases reported in developing nations, Eastern Europe, and the Southern United States. In the absence of appropriate antibiotic treatment, T. pallidum establishes a lifelong chronic infection that may progress to the debilitating and potentially fatal tertiary disease in approximately one third of infected individuals. Apart from the serious nature of the disease itself, a number of studies suggest syphilis infections may increase the risk of acquisition and transmission of human immunodeficiency virus. The first step in establishing a T. pallidum infection is bacterial attachment and colonization of epithelial surfaces. Consequently, a logical approach for preventing T. pallidum infection is to develop methodologies for inhibiting bacterial attachment to host cells. The studies outlined in this proposal focus upon the identification of T. pallidum adhesins involved in host cell attachment, and specifically those involved in attaching to components of the extracellular matrix (ECM). The adhesins of T. pallidum will be identified using a variety of experimental techniques, including affinity chromatography and expression library screening. Putative adhesins will be expressed in a recombinant form using heterologous expression systems. These proteins will subsequently be investigated for their involvement in host cell attachment by determining their binding potential to host cells and ECM components. Confirmed adhesins will be tested for their ability to complement the non-adherent treponeme T. phagedenis biotype Reiter, and the molecular regions of the treponemal adhesins and ECM components responsible for attachment will be identified. The T. pallidum adhesins will also be analyzed for their immunoprotective potential in rabbit immunization and challenge experiments, and specifically for their ability to prevent treponemal infection. The long-term objective of the studies outlined in this proposal is to identify T. pallidum ECM-adhesins, which will

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Syphilis

in turn help to further our under-standing of the molecules involved in T. pallidum pathogenesis and identify potential syphilis vaccine candidates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AMERICANS

GENETIC

TESTING/HEARING

IMPAIRMENT

IN

AFRICAN

Principal Investigator & Institution: Robin, Nathaniel H.; Associate Professor; Genetics; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant) African Americans (AA) as a group distrust the medical establishment. The reasons have been discussed in editorials and opinion papers, and include unfortunate historical events like the Tuskegee syphilis study and the Sickle Cell screening program. One undesirable consequence of this mistrust is that AA as a group have been hesitant to participate in biomedical research studies. Consequently, many medical advances have not had a direct benefit for this population. One example of this is the genetic basis for hearing impairment (HI). Over 60 hearingrelated genes have been identified in the past decade, and genetic testing is now available for one, GJB2. Studies among populations of Northern European extraction have shown that GJB2 mutations cause about 55% of nonsyndromic HI. No similar discovery has occurred for AA, as in limited studies GJB2 mutations have not been seen in AAs. Therefore, despite the many discoveries, there has been little advance in the genetics of HI in AA. A recent report suggested that mutations in a related gene, GJA1, may be more common in deaf/hard of hearing (D/HOH) AA, but this study was limited, as only 26 D/HOH AA were tested. In this proposal, we will examine the interrelated issues of AA's willingness to participate in research and the genetic basis of HI in AA. We will survey D/HOH AA and their families on their attitudes towards research and genetic testing for HI. Those subjects that complete the survey will then be offered free research-based genetic testing for several HI-related genes, GJB2, GJB6, and GJAI. Dr. Richard Smith at the University of Iowa will do the genetic testing. Offering the research based genetic testing will yield two valuable results. First, we will gain insight into why some AAs are unwilling to participate in research by comparing the results of those that agree to participate and those that decline. Second, by the results of the genetic testing, we will determine the frequency of mutations in GJB2, GJB6, and GJA1 among D/HOH AA. Subjects will be notified of their test results and offered free genetic counseling to have the results explained. From these results we will gain insight into why AA will/will not participate in research studies, and into their attitudes toward genetic testing for HI. Furthermore, these results will determine the role of mutations in GJB2, GJB6, and GJA1 in HI in AA. Together, these results will lead to more efficient genetic testing for HI in this population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GORDON CONFERENCE--BIOLOGY OF THE SPIROCHETES Principal Investigator & Institution: Weis, Janis J.; Professor; Gordon Research Conferences Box 984, 512 Liberty Ln West Kingston, Ri 02892 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2002 Summary: The fifth Gordon Research Conference on the Biology of Spirochetes will be held in January 2002 in Ventura, California. The Biology of Spirochetes Conference is unique. This is the only ongoing international meeting devoted to discussions on basic research of all medically important and biologically relevant spirochetes, a unique

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group of Eubacteria. Many spirochetes are pathogens and cause a variety of diseases, including syphilis, Lyme disease, relapsing fever, leptospirosis, periodontal disease, digital dermatitis of cattle, and swine and human dysentery. Historically, spirochetes have been difficult to study. These bacteria often have fastidious nutritional requirements and some have yet to be successfully cultured in vitro. Methods for genetic manipulation and mutational analysis of several spirochete species do not exist. The opportunity for exchange of ideas among groups working on different spirochetes has been one of the greatest benefits of past conferences, particularly in the area of new techniques for genetic manipulation. The application of genetic advancements and the availability of genomic sequences of Borrelia burgdorferi, Treponema pallidum, T. denticola, and new sequencing projects in Leptospira spp, are proving a wealth of new information. Combined, these data are being integrated into ongoing studies on the physiology, structure, pathogenesis, and immunobiology of these bacteria. Each of the previous Biology of Spirochetes conferences have been highly successful, receiving high praise by attendees, forging new collaborations, providing a forum for presenting stateof-the-art research on these bacteria, and helping to set new research directions. As in previous conferences, we expect attendance at the 2002 conference to reach the maximum of 150 faculty, graduate students, postdoctoral fellows, and industrial scientists. A broad spectrum of scientists representing different research interests, geographic locations, and seniority will be invited to attend. Special efforts will be made to insure strong attendance of young investigators (graduate students, post-docs and junior faculty), and achieve a balance in gender and ethnicity of attendees. The oral and poster-presentations are organized to provide many opportunities for discussion, the exchange of ideas, and development of collaborations. Funding from the National Institutes of Health is requested to partially offset the travel and registration expenses of the participating graduate students, fellows, and junior faculty members. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HIV AND THE SEXUAL NETWORKS OF IDUS AND DRUG-USING MSM Principal Investigator & Institution: Ouellet, Lawrence J.; Epidemiology and Biostatistics; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Preventing the sexual transmission of HIV is essential if the United States is to further reduce HIV incidence. Among drug-using populations, however, the sexual transmission of HIV is understudied. The proposed five-year study focuses on injection drug users (IDUs) and drug-using men who have sex with men (MSM) to examine the sexual diffusion of HIV within and across drugusing population subgroups and to non-drug using and non-MSM populations. Our approach combines 1) behavioral epidemiology, 2) two-types of social network analyses with strong geographic mapping components [including the ability to link geographic location with local socio-economic and health data], 3) mathematical modeling, and 4) and biologic testing for HIV, hepatitis B (HBV) and C (HCV), syphilis, chlamydia and gonorrhea. The study proposes a cross sectional survey of 2500 IDUs and about 562 of their non-injecting sex partners, and 3000 MSM and about 450 of their female sex partners. Participants will be recruited through respondent-driven sampling (RDS) [1-3] at six racially and ethnically diverse sites across Chicago. As a feature of RDS, sampling weights will be calculated to adjust for unequal probabilities of selection based on variations in network size, strength of in-group affiliation and recruitment effectiveness, and the data will be post-stratified so the results can be generalized to the population of

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IDUs and drug-using MSM. HIV specimens from participants with newly diagnosed infections will be tested using the serologic testing algorithm for recent HIV seroconversion (STARHS), and HIV incidence computed from the results. HIV genotyping and phenotyping, RNA viral load testing, and cellular immune panels will be used to characterize newly diagnosed infections by drug resistance, infectiousness, and immune system suppression. Test results for other STIs will be used to better characterize the potential for future diffusion of HIV or increased vulnerability to infection with HIV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RECRUITS

HIV/AIDS

PREVENTION

AMONG

ANGOLAN

MILITARY

Principal Investigator & Institution: Bing, Eric G.; Director, Collaborative Alcohol; None; Charles R. Drew University of Med & Sci 1621 E 120Th St Los Angeles, Ca 90059 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (Provided by applicant): HIV/AIDS has had a devastating impact on subSaharan Africa. With just 8 percent of the world's population, sub-Saharan Africa accounts for 70 percent of all the world's 36.1 million HIV/AIDS cases. Despite the high HIV prevalence rates of as much as 35 percent in neighboring countries, the reported HIV prevalence rate for Angola is reported to be only 3 percent. This relatively low rate may be due to the on-going civil war that has restricted population mobility. Therefore, there is at present a window of opportunity to save Angola from the devastation that AIDS has wrought on other areas of the sub-continent. Our international team of Angolan and American researchers proposes to test the effectiveness of a multi-session HIV/STD prevention intervention on reducing high-risk sexual behaviors and the incidence of sexually transmitted diseases among Angolan military recruits. Our 3 specific aims are: (1) To test the effectiveness of a cognitive-behaviorally focused intervention designed to reduce high-risk sexual behaviors and the incidence of STDs (such as HIV, chlamydia, gonorrhea, and syphilis) immediately following and at 3 and 6 months post-intervention; (2) To determine the degree to which the individual components of the intervention (information about HIV/STDs, motivation to reduce risk of infection, and skills at condom use) produce a reduction in high-risk sexual behaviors and the incidence of STDS; and, (3) To determine if predisposing factors such as sociodemographic and personal characteristics, psychiatric symptoms and disorders, alcohol use and history of STDs moderate the effect of the intervention on sexual risk taking and STD incidence. We will conduct the intervention in the Cabinda Province of Angola. Though Cabinda is the smallest Angolan province, 45 percent of all the country's AIDS cases have been reported there. To better understand the context of HIV prevention for the Angolan military, in Phase 1 we will conduct 5 focus groups with new recruits (2 groups), experienced soldiers, military sergeants, and HIV-positive soldiers. We will use the information gained in the focus groups to modify the content of the instruments to be used in a survey and the proposed intervention. In Phase 2, we will pilot test the survey instrument with 100 soldiers as well as the intervention. The proposed intervention, Salva Vida (Save Life), will consist of 4 sessions (1 session each week) and 1 booster session 6 weeks after the final session. In Phase 3, we will test the intervention with a total of 400 military men, with 200 being assigned to the intervention and 200 to the control condition, which will have a general health promotion focus. If this intervention is effective among military recruits in Angola, it may have applicability to many developing nations throughout the world battling HIV with scarce resources and little hope of treatment.

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

Project Title: HIV/STD RISK BEHAVIORS IN METHAMPHETAMINE USER NETWORKS Principal Investigator & Institution: Shoptaw, Steven; Associate Research Psychologist; Psychiatry; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): The proposed study will launch a multidisciplinary effort to examine the diffusion of HIV and sexually transmitted diseases (STDs including gonorrhea, chlamydia, and syphilis) in drug users in L.A. County to identify the individual level factors, partner-level factors, and environmental factors that promote the spread of these diseases. L.A. County is the second largest epicenter of AIDS cases in the nation, yet injection drug use (IDU) accounts for only a minority (13%) of cases, while the majority of cases involve MSM (70%). Recent, disproportionate increases of HIV infection for women and people of color in L.A. County imply the virus is moving from relatively contained groups into larger segments. This 5-year study proposes to establish a representative cohort of individuals thought to represent the behavioral "bridges" for these pathogens to enter the larger population: drug using MSM (n=240), drug using MSM/W (n=240) a comparison group of non-drug using MSM/W (n=240), and the male (n=288) and female (n=192) sexual partners of these individuals (total=1,200). Assessments will be collected at baseline, 6- and 12-months after enrollment. Data collected will address these study aims: (1) Measure associations between drug involvement (methamphetamine user, other drug user, non-drug user), IDU status, sexual risk behavior (MSM, MSM/W, WSM), and HIV/STDs; (2) Evaluate the types of sexual partnerships and dynamics of the partnerships of these individuals and how these are associated with HIV/STD transmission; and (3) Apply mathematical models to the data on partnerships to study how the incidence of HIV/STDs reflect the size and interconnectedness of the sexual networks of each of the groups and to determine the impact of sexual network structure in future transmission of HIV in L.A. within and beyond MSM and heterosexual drug using groups. The study will use methods of behavioral epidemiology, ethnography, viral analysis of HIV, and mathematical modeling to yield a comprehensive set of information to predict the spread of HIV and STDs from sexual networks of high HIV prevalence (drug using MSM) to those of low prevalence (heterosexuals). Outcomes from the proposed cohort study of IDU and non-lDU methamphetamine-using MSM and MSM/W and their sexual partners should provide evidence to guide policy and prevention efforts in response to the spread of HIV and STDs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNE MECHANISMS IN EXPERIMENTAL SYPHILIS Principal Investigator & Institution: Lovett, Michael A.; Professor of Genetics; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-JUN-1978; Project End 31-JAN-2005 Summary: To study the role of the rare T. pallidum (Tp) outer membrane (OM) spanning proteins in pathogenesis and immunity, we isolated Tp OM vesicles (OMV). OMV porin activity resides in a 31 kDa protein, Tromb1. Native Tromp1 is 31, 510 Da, and is processed from a 33,571 Da precursor. While native Tromp1 is hydrophobic, and

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trimeric, urea creates a hydrophilic monomer, indicating that the hydrophobicity of the native protein is conformationally determined. Monomeric rTromp1 has no poring activity and is hydrophilic. Renatured rTromp1 is trimeric and hydrophobic, with porin activity like native Tromp1. Renatured rTromp1 formed intra membranous particles in proteoliposomes. OMV were used to generated mouse antiserum that showed a 100% killing endpoint titer 32 times greater than time of immune rabbit serum (IRS). The OMV ant- serum bound Tromp1, Tromp2, and four lipoproteins were fully removed, while Tromp antibodies remained. The adsorbed serum showed no reduction in its high-titered treponemicidal activity, suggesting that Tromp1 and/or Tromp2 are the targets of this activity. Treponemicidal activity greater than that found in IRS has never previously been demonstrated. Our specific aims are therefore: 1. Determine the significance and basis of OMV induced treponemicidal antibodies. We will learn if OMV can convey protection in experimental syphilis. The possibility that treponemicidal antibodies. We will learn if OMV can covey protection in experimental syphilis. The possibility that there are relevant OMV proteins other than Tromp1 and 2 will be rigorously considered. The role of OMV in pathogenesis will be addressed by use of adherence and invasion assays. 2. Determine the role of Tromp1 in pathogenesis and immunity. Mass spectrometry adapted to nanogram amounts will be used to insure that rTromp1 faithfully duplicates the primary structure of native Tromp1. The ability of renatured rTromp1 and native Tromp1 to induce treponemicidal antibodies and protective immunity will be assessed, along with the role of Tromp1 in pathogenesis. 3. Determine the role of Tromp2 in pathogenesis and immunity. Tromp2 has conformationally determined hydrophobicity, but lacks porin activity. Tromp2 is considerably less abundant than Tromp1. Definitive determination of the primary structure of mature Tromp2 will be used as the basis for creating a rTromp2 whose primary structure is identical to the native protein. rTromp2 will be renatured and studied as outlined for rTromp1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPACT OF SOCIAL NETWORKS ON SYPHILIS TRANSMISSION Principal Investigator & Institution: Rompalo, Anne M.; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: (Adapted from the Applicant's Abstract): The investigators propose to examine the role of social context and social influence on syphilis transmission in Baltimore. Currently, Baltimore has the Nation's highest rates for newly acquired primary and secondary syphilis. The goals of this study are, first, to examine the social context of syphilis risk through the assessment of social and sexual network characteristics. In collaboration with he Baltimore City Health Department (BCHD), the investigators will recruit between 400 and 1200 patients who present to the BCHD Sexually transmitted Diseases (STD) clinics for evaluation and treatment of primary and/or secondary stage syphilis. The investigators will collect specimens from these patients' syphilis lesions for restriction fragment length polymorphism (RFLP) analysis, and conduct social and sexual network interviews with these syphilis patients and their social/sexual network members. Using Geographic Information System (GIS), the investigators will map the social and sexual networks. This will allow us to track and compare possible syphilis transmission through both network types and to examine social structural factors, especially drug use, which may be associated with disease transmission and risk behaviors. Social context data will be confirmed by biologicallybased strain typing. The investigators propose to apply the RFLP technique in

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collaboration with Dr. Sheila Lukehart at the University of Washington to determine the prevalence of and factors associated with genetic clustering of syphilis in Baltimore over time. The investigators will determine if different RFLP profiles exist m Baltimore, use GIS to plot their spatial distribution and evaluate the relationship of social networks to clusters of infections. This will be the first time that a biological marker of transmission will serve to validate epidemiological defined transmission groups and thus improve our ability to delineate the sexual, social and personal network characteristics associated with syphilis transmission. The investigators are currently funded to examine the role of social context on gonorrhea transmission. As a second goal of this study will be to compare the social context of syphilis risk to that of gonorrhea risk and to determine and compare the role of drug use and other social factors in the social context of both sexually transmitted diseases. Thus, the investigators propose to compare the efficacy of detecting early infectious (primary and secondary stage) syphilis cases by interviewing and screening social network members of early syphilis index cases compared to that of standard sexual partner notification techniques. The proposed project seeks five years of support to map, analyze and compare syphilis cases within social and sexual networks. Data collected in this proposal data may be applied to modify current methods of syphilis contact tracing and develop more effective future preventive and intervention strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INCREASING PARTICIPATION OF MINORITY RESEARCHERS IN ETH Principal Investigator & Institution: Sander, Linda D.; Pediatrics; Meharry Medical College 1005-D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: The media exposure of the Tuskegee Syphilis Experiments in 1974, and rare but well-publicized reports of research subjects' deaths, have contributed to mistrust by the public, and in particular minorities, of human subjects research and researchers. Efforts to overcome barriers of mistrust among minorities and medically underserved individuals are needed, so that the expectation of respectful medical care, and the benefits and altruistic satisfaction that may accompany human subjects research, may be shared more justly. Accordingly, recognition has grown in recent years of the importance of understanding the needs, interests, and perspectives about ethical research among individuals belonging to minority and medically underserved populations. To participate in this aim, Meharry Medical College, an historically black institution committed to the education and service of minority and underserved populations, has established the Program in Clinical and Research Ethics. This program addresses the need for increased minority involvement and leadership in clinical research ethics. Expertise and dialogue in research ethics are sought among Meharry's professional and student communities, as well as local community members and neighboring institutions. Collaboration with Vanderbilt University Medical Center and the New Orleans District FDA (serving Nashville) facilitates the exchange of ideas among professional communities. This collaborative arrangement serves both to help increase the interests and expertise of minority medical professionals in research ethics, and to increase the awareness among all human subjects researchers of the ethical needs of minority and underserved research subjects. Two main venues for research ethics education are offered. 1. For active researchers, IRB members, community members and students, we offer symposia on ethical issues in human subjects research. 2.

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Syphilis

For senior medical students and others, an innovative month long clinical elective in Clinical and Research Ethics is offered twice a year. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: 'LYME DISEASE: A POSSIBLE TEST FOR CURE Principal Investigator & Institution: Philipp, Mario T.; Chairman; None; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-MAY-2004 Summary: (provided by applicant): It would be immensely useful for the management of Lyme disease (LD) treatment to have available a test for cure. Such a test could be employed not only to ascertain if treatment of acute LD was successful, thereby preventing the transition to the chronic, more intractable form of the disease, but also to distinguish among the possible etiologies of the so-called post-treatment LD syndrome. The PI and coworkers recently developed a sensitive and specific enzyme-linked immunosorbent assay (ELISA) for the serological diagnosis of LD. The test is based on the detection of antibody (Ab) to an immunodominant, invariable region (lR) of the lipoprotein VIsE. VIsE is the molecule that undergoes antigenic variation in Borrelia hurgdorfen (the etiologic agent of LD). A peptide (C6) representing the invariable region 6 (IR6) of VIsE serves as antigen. It is hypothesized that, because the spirochete should not simultaneously express on its surface more than one (or a few) VIsE variant(s) at any time, the VIsE lipoprotein must be rapidly turned over and degraded by the spirochete as new variants are progressively expressed. As a consequence of this postulated intrinsic instability, VIsE should be scarce on dead or dying spirochetes, and secondary Ab responses to the C6 peptide should decline in unison with the infection's demise, following antibiotic treatment. It is further hypothesized that the decline in titer of the C6 Ab as a function of time after treatment may serve as a test for Lyme disease cure. Preliminary results indicate that the C6 ELISA titer in cured patients falls by a factor greater or equal than 4 whereas for treatment-resistant patients the fall is by a factor