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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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