LymeNet Newsletter Volume 2 Issue 19

Volume: 2
Issue: 19
Date: 16-Nov-94

Table of Contents:

I. NIAID and Lyme Disease Research - Historical Perspective II. NIAID Activities FY 1991 through FY 1994 III. Selected NIAID-Supported Research Highlights IV. FY94 NIH Extramural Research Grants V. About The LymeNet Newsletter

Newsletter:

*********************************************************************** * The National Lyme Disease Network * * LymeNet Newsletter * ***********************************************************************

IDX# Volume 2 - Number 19 - 11/16/94 IDX# INDEX IDX# IDX# SPECIAL ISSUE IDX# NIH RESEARCH UPDATE IDX# IDX# I. NIAID and Lyme Disease Research - Historical Perspective IDX# II. NIAID Activities FY 1991 through FY 1994 IDX# III. Selected NIAID-Supported Research Highlights IDX# IV. FY94 NIH Extramural Research Grants IDX# V. About The LymeNet Newsletter IDX#

This issue is dedicated to providing readers with information on the Lyme Disease work being performed and/or funded by the National Institutes of Health. This information has been provided to the LymeNet Newsletter by the NIH.

I. NIAID and Lyme Disease Research - Historical Perspective ==============================================================

The etiologic agent for Lyme disease, Borrelia burgdorferi, was isolated and identified in 1981 by NIAID Rocky Mountain Laboratories (RML) researchers Willy Burgdorfer and Alan Barbour working with N.Y. State Health Department researchers Jorge Benach and Edward Bosler.

NIAID has maintained an intramural Lyme disease research effort at the RML since 1981. Currently the RML Lyme disease effort is funded at $1,606,000. NIAID has supported extramural Lyme disease research since 1985. Support has increased dramatically, as reflected in the figures below. NIAID support rose from two projects in 1987 to 34 in FY93. The FY93 funding level was $7,948,000.

NOTE: INSERT GRAPHIC (BAR CHART)- LYME BORRELIOSIS NIAID SUPPORT, 1987-1993 (In Thousands)

1987 $1,379 1988 $1,444 1989 $2,268 1990 $4,874 1991 $6,557 1992 $6,819 1993 $7,948

II. NIAID Activities FY 1991 through FY 1994 ==============================================

A State-of-the-Art Workshop on the Diagnosis and Treatment of Lyme Disease was held in March 1991 in cooperation with the National Institute of Arthritis and Musculo- skeletal and Skin Diseases (NIAMS). The workshop resulted in the publication of a newsletter on the same topic, which was distributed to 65,000 physicians.

NOTE: INSERT GRAPHIC (BAR CHART)- RESEARCH PROJECTS ON LYME BORRELIOSIS 1987-1993

1987 6 1988 8 1989 10 1990 22 1991 27 1992 31 1993 34

In 1993, an NIH Lyme Disease Coordinating Committee was established. The Chairperson is Dr. John La Montagne, director of the Division of Microbiology and Infectious Diseases.

On July 1, 1993, NIAID convened a workshop on vaccine research and trial designs. Since then, two pharmaceutical companies have initiated Phase III trials of two OspA-based candidate Lyme disease vaccines.

NIAID and NIAMS issued a Request for Applications entitled "Immune Responses to Lyme Disease Infection and Vaccination." Eight new projects will be funded by the end of FY94, two by NIAMS and six by NIAID.

In 1994, NIAID also issued a Request for Proposals entitled, "Animal Models for Chronic Lyme Disease." Two new contracts will be awarded before the end of FY94.

NIAID funded a research project to establish the role of borrelia in chronic Lyme disease patients. This award should have a major impact on resolving issues of treatment and diagnosis in late-stage disease.

The NIAID Program Announcement, "Epizootiology and Transmission of Lyme Borreliosis," continues to encourage research in this area. In addition, NIAID is planning cooperative activities with NASA to explore the uses of GIS/remote sensing to define the distribution of the tick vector in endemic areas.

NIAID is co-sponsoring a Program Announcement entitled "Neurological Aspects of Lyme Disease" with the National Institute of Neurological Disorders and Stroke.

NIAID convened a workshop on chronic Lyme disease on Jan. 31, 1994, to discuss clinical trial designs and therapies.

In April 1994, intramural and extramural staff from NIAID, the Centers for Disease Control and Prevention, the Food and Drug Administration, the Association of State and Territorial Public Health Laboratories, and NIAID-funded investigators drafted interim recommendations for Western blot diagnosis of Lyme disease. A second meeting will take place in October, 1994 to review the recommendations, which are expected to clarify issues of seropositivity and facilitate treatment for patients.

NIAID co-sponsored and participated in the VI International Conference on Lyme Borreliosis (June 19-22, 1994) in Bologna, Italy.

III. Selected NIAID-Supported Research Highlights ==================================================

Drs. Benjamin Luft and Raymond Dattwyler at the State University of New York at Stony Brook carried out a comparative treatment study of amoxicillin and azithromycin on 217 patients with erythema migrans. Relapse was significantly more frequent in patients treated with azithromycin. Antibody testing did not appear useful in assessing disease activity in patients treated within the first few weeks of infection. Drs. Luft and Dattwyler have developed candidate vaccines based on chimeric proteins generated from different borrelial lipoproteins and different strains. These proteins are immunogenic and inhibit growth of multiple species of borrelia. This is in contrast to the current generation of OspA vaccines, which appear to be serotype specific.

Dr. Mark Klempner of Tufts University has reported that although B. burgdorferi lacks the usual surface bacterial proteases for breaking down host tissues, the bacterium makes use of human proteases. B. burgdorferi subverts the host fibrinolytic system by binding non-immunogenic host proteases, which allows rapid spreading through the extracellular matrix and basement membrane components.

Dr. Richard Flavell and colleagues at Yale and Harvard used a mouse model to develop an OspA-based vaccine. They found that immunization with recombinant OspA or B was more effective than expected and that destruction of the bacteria within the tick prior to transmission may be the main mode of protection from infection.

Dr. Andrew Spielman, Harvard University, has identified people co-infected with Lyme disease and babesiosis, the latter caused by Babesia microti. Co-infection appeared to result in more severe and prolonged illness than did Lyme disease alone, suggesting that babesial infection may impair host immunity in a manner similar to malaria.

-- NIAID, a component of the National Institutes of Health, supports research on AIDS, tuberculosis and other infectious diseases as well as allergies and immunology. NIH is an agency of the U.S. Public Health Service, U.S. Department of Health and Human Services.

August 1994

IV. FY94 NIH Extramural Research Grants =========================================

ANDERSON, JOHN YALE UNIVERSITY $170,947 FY94 LYME DISEASE--PATHOGENESIS AND PROTECTION SUB TITLE CORE--ENTOMOLOGY AND BACTERIOLOGY

APPEL, MAX J CORNELL UNIVERSITY ITHACA $246,001 FY94 ANIMAL MODELS FOR CHRONIC LYME DISEASE BARBOUR, ALAN G U. OF TEXAS HLTH SCI CTR $183,884 FY94 GENETIC AND PATHOGENICITY OF BORRELIA BURGDORFERI BARTHOLD, STEPHEN YALE UNIVERSITY $170,947 FY94 LYME DISEASE--PATHOGENESIS AND PROTECTION SUB TITLE MOUSE MODEL OF LYME BORRELIOSIS

BARTHOLD, STEPHEN W YALE UNIVERSITY $396,984 FY94 ANIMAL MODELS FOR CHRONIC LYME DISEASE BARTHOLD, STEPHEN W YALE UNIVERSITY $239,278 FY94 MOUSE MODEL OF LYME BORRELIOSIS BARTHOLD, STEPHEN W YALE UNIVERSITY $1,025,683 FY94 LYME DISEASE--PATHOGENESIS AND PROTECTION

COYLE, PATRICIA K SUNY STONY BROOK $249,117 FY94 CHRONIC FATIGUE IN LYME DISEASE FIKRIG, EROL YALE UNIVERSITY $114,800 FY94 IMMUNIZATION AGAINST NATURALLY TRANSMITTED LYME BORRELIOSIS

FISH, DURLAND YALE UNIVERSITY $215,034 FY94 POPULATION REGULATION OF THE DEER TICK, IXODES DAMMINI FLAVELL, RICHARD YALE UNIVERSITY $170,947 FY94 LYME DISEASE--PATHOGENESIS AND PROTECTION SUB TITLE A RECOMBINANT VACCINE FOR LYME BORRELIOSIS FURIE, MARTHA B SUNY STONY BROOK $129,606 FY94 EFFECT OF BORRELIA ON ENDOTHELIAL CELLS AND LEUKOCYTES ISBERG, RALPH R TUFTS UNIVERSITY $144,425 FY94 CELLULAR ENTRY AND ADHESION OF BORRELIA BURGDORFERI JOHNSON, RUSSELL C U. OF MN TWIN CITIES $151,340 FY94 ANTIGENIC/IMMUNOGENIC COMPONENTS--BORRELIA BURGDORFERI KANTOR, FRED YALE UNIVERSITY $170,947 FY94 LYME DISEASE--PATHOGENESIS AND PROTECTION SUB TITLE PROTECTIVE EPITOPES IMPORTANT IN LYME BORRELIOSIS
KEIRANS, JAMES E GEORGIA SOUTHERN U. $103,377 FY94 TICK SYSTEMATICS ON A GLOBAL BASIS KLEMPNER, MARK S NEW ENGLAND MEDICAL CENTER $204,473 FY94 PATHOGENESIS OF LYME BORRELIOSIS

LANE, ROBERT S U. OF CA BERKELEY $213,815 FY94 LYME DISEASE IN WESTERN USA--ECOLOGY AND EPIDEMIOLOGY LIN, LILY STERITECH, INC. $239,032 FY94 METHODS FOR PCR SAMPLE PREPARATION--HEME NEUTRALIZATION

LUFT, BENJAMIN J SUNY STONY BROOK $489,599 FY94 DEVELOPMENT OF DIAGNOSTICS FOR LYME BORRELIOSIS MALAWISTA, STEPHEN YALE UNIVERSITY $170,947 FY94 LYME DISEASE--PATHOGENESIS AND PROTECTION SUB TITLE PROBES FOR BORRELIA BURGDORFERI DNA IN TICKS, MICE AND MEN MATHER, THOMAS N U. OF RHODE ISLAND $94,040 FY94 DYNAMICS OF LYME DISEASE SPIROCHETE TRANSMISSION MC LAIN, DENSON K GEORGIA SOUTHERN U. $81,651 FY93 STRUCTURE AND COMPOSITION OF THE GENOME OF IXODID TICKS NEEDHAM, GLEN R OHIO STATE U. $1,000 FY94 IX INTERNATIONAL CONGRESS OF ACAROLOGY NORGARD, MICHAEL V U. OF TEXAS SW MED CTR/DL $210,211 FY94 MEMBRANE PROTEINS OF BORRELIA BURGDORFERI OLIVER, JAMES H, JR GEORGIA SOUTHERN U. $164,508 FY94
IXODES TICKS AND BORRELIA BURGDORFERI PERSING, DAVID H MAYO FOUNDATION $279,956 FY94 MULTILOCUS MOLECULAR DETECTION OF BORRELIA BURGDORFERI PHILIPP, MARIO T TULANE U. OF LA $162,613 FY94 SECOND-GENERATION VACCINES AGAINST LYME DISEASE SCHELL, RONALD F U. OF WI MADISON $135,540 FY94 IMMUNE RESPONSES TO BORRELIA BURGDORFERI--LYME DISEASE

SCHWARTZ, BRIAN JOHNS HOPKINS U. $110,693 FY94 ANTITICK ANTIBODY IN LYME DISEASE RESEARCH

SMITH, GARY UNIVERSITY OF PA $199,183 FY94 DEVELOPMENT AND MORTALITY OF IXODES DAMMINI

SPIELMAN, ANDREW HARVARD UNIVERSITY $202,514 FY94 HOST ABUNDANCE AND TRANSMISSION OF IXODES-BORNE ZOONOSES SPIELMAN, ANDREW HARVARD UNIVERSITY $158,962 FY94 MECHANISM OF TRANSMISSION OF THE AGENT OF LYME DISEASE TITUS, RICHARD G HARVARD UNIVERSITY $222,596 FY94 SAND FLY AND TICK SALIVA AND DISEASE WEIS, JANIS J U. OF UTAH $154,036 FY94 BORRELIA BURGDORFERI MITOGEN IN DEVELOPMENT OF ARTHRITIS WILSON, MARK L YALE UNIVERSITY $124,765 FY94 ENVIRONMENTAL DETERMINANTS OF IXODES DAMMINI EXPANSION

BENACH, JORGE L NY STATE DEPT OF HEALTH $99,275 FY94 BORRELIA BURGDORFERI--INVASION AND CHRONICITY COOPER, SHELDON M U. OF VT & ST AGRIC COLL $227,313 FY93 CLONALITY AND TCR GENES OF RA AND LYME SYNOVIAL T CELLS COYLE, PATRICIA K SUNY STONY BROOK $124,170 FY94 IMMUNE COMPLEX ANALYSIS IN LYME NEUROBORRELIOSIS GRAVALLESE, ELLEN M BRIGHAM AND WOMEN'S HOSP $119,193 FY94 ARTHRITIS AND MUSCULOSKELETAL DISEASES CENTER SUB TITLE FEASIBILITY STUDY--MECHANISMS OF DISEASE IN MOUSE MODEL OF LYME DISEASE HABICHT, GAIL S SUNY STONY BROOK $129,363 FY93 LYME DISEASE--DEVELOPMENT OF SKIN LESIONS AND ARTHRITIS

KLEMPNER, MARK S NEW ENGLAND MEDICAL CENTER $239,289 FY94 DIAGNOSIS OF EARLY LYME DISEASE LIANG, MATTHEW H BRIGHAM AND WOMEN'S HOSP $119,193 FY94 ARTHRITIS AND MUSCULOSKELETAL DISEASES CENTER SUB TITLE EPIDEMIOLOGY OF CHRONIC LYME DISEASE MALAWISTA, STEPHEN YALE UNIVERSITY $202,697 FY94 PATHOGENESIS OF LYME DISEASE--MOLECULAR PROBES NADELMAN, ROBERT B NEW YORK MEDICAL COLLEGE $179,146 FY94 CONTROLLED TREATMENT TRIAL OF PATIENTS WITH LYME DISEASE

PERSING, DAVID H MAYO FOUNDATION $73,637 FY94 MOLECULAR DIAGNOSIS AND MONITORING OF LYME DISEASE PICKEN, ROGER N RUSH UNIVERSITY $98,828 FY94 LYME DISEASE DIAGNOSIS BY PCR/DNA PROBE SYSTEM SCHWARTZ, IRA S NEW YORK MEDICAL COLLEGE $174,422 FY94 NUCLEIC ACID-BASED DIAGNOSTIC PROBES FOR LYME DISEASE STEERE, ALLEN C NEW ENGLAND MEDICAL CENTER $277,969 FY94 LYME ARTHRITIS--A NEW EPIDEMIC DISEASE WINCHESTER, ROBERT COLUMBIA UNIVERSITY $246,602 FY94 IMMUNOGENETIC BASIS OF LYME DISEASE SUSCEPTIBILITY BOOTHBY, JOHN T SAN JOSE STATE U. $81,304 FY94 INTERDISCIPLINARY BIOMEDICAL RESEARCH PROGRAM SUB TITLE BORRELIA BURGDORFERI HSP-1 IN LYME DISEASE PRYOR, STEPHEN C COLLEGE AT OLD WESTBURY $150,468 FY94
MINORITY BIOMEDICAL RESEARCH SUPPORT PROGRAM SUB TITLE BIOCHEMICAL GENETICS OF ARTHROPOD DISEASE VECTORS STROBINO, BARBARA A NEW YORK MEDICAL COLLEGE $237,426 FY94 MATERNAL LYME DISEASE AND CONGENITAL HEART ABNORMALITIES STRICKLAND, G THOM U. OF MARYLAND BALT PROF $195,053 FY94 PATIENT OUTCOMES WITH ANTIBIOTIC THERAPY OF LYME DISEASE MURPHY, JAMES MA INSTITUTE OF TECH $92,407 FY94 DIAGNOSTIC AND INVESTIGATIVE LABORATORY SUB TITLE DEVELOPMENT OF A MOUSE MODEL FOR LYME DISEASE PHILIPP, MARIO T TULANE U. OF LA $95,884 FY94 REGIONAL PRIMATE RESEARCH CENTER SUB TITLE DEVELOPMENT OF A VACCINE AGAINST LYME DISEASE SHAPIRO, EUGENE YALE UNIVERSITY $14,458 FY94 GENERAL CLINICAL RESEARCH CENTER SUB TITLE LYME DISEASE IN CHILDREN
WEIS, JANIS J U. OF UTAH $16,092 FY94 GENERAL CLINICAL RESEARCH CENTER SUB TITLE IDENTIFICATION OF VIRULENCE FACTORS OF BORRELIA BURGDORFERI OLIVER, JAMES H, JR GEORGIA SOUTHERN U. $20,000 FY94 TICK VECTORS AND THE LYME DISEASE SPIROCHETE IN RUSSIA

More Recently Funded Projects:

Mark Klempner Tufts Univ. Med. Ctr. Lyme Disease: Spirochete Invasion and Host Immunity $360,076

Frank Gherardini University of Georgia, Athens Low-Passage-Associated Proteins from B. burgdorferi $104,720

Steven Nickell Johns Hopkins University, Sch. Public Hlth. T-Cell-Dependent Modulation of Exp'l. Lyme Arthritis $149,778

Alan Barbour Univ. Texas Hlth Sci Ctr, San Antonio Interface of Borrelia Surface Proteins and Antibodies $233,170

Bejamin Luft SUNY, Stony Brook Vaccine Intervention for Lyme Borreliosis $137,740

Thomas Mather University of Rhode Island Role of Tick Saliva in Lyme Disease and Vaccine Strategy $169,188

James Miller* UCLA Rabbit Lyme Disease Model: Pathogenesis and Immunity $279,262

*Paid from non-RFA funds in FY94.

Note: Two additional RFA applications were funded by NIAMS (Janis Weis, Univ. Utah and Ralph Budd, UVM).

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