LymeNet Newsletter Volume 4 Issue 11

Volume: 4
Issue: 11
Date: 05-Aug-96

Table of Contents:

I. INFECTION: Physician Preferences in the Diagnosis and Treatment of Lyme Disease in the United States II. NIAID: NIAID Awards Contract for Post-Lyme Disease Syndrome Studies III. NIAID: Questions and Answers About NIAID's Chronic Lyme Disease Study IV. AP: N.J. Gov. Has Lyme Symptoms V. About The LymeNet Newsletter

Newsletter:

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

IDX# Volume 4 - Number 11 - 8/05/96 IDX# INDEX IDX# IDX# I. INFECTION: Physician Preferences in the Diagnosis and IDX# Treatment of Lyme Disease in the United States IDX# II. NIAID: NIAID Awards Contract for Post-Lyme Disease Syndrome IDX# Studies IDX# III. NIAID: Questions and Answers About NIAID's Chronic Lyme IDX# Disease Study IDX# IV. AP: N.J. Gov. Has Lyme Symptoms IDX# V. About The LymeNet Newsletter IDX#

QUOTE OF THE WEEK:

"Scientific thought is not an accompaniment or condition of human progress, but human progress itself."

William Kingdon Clifford, 1945-1879

I. INFECTION: Physician Preferences in the Diagnosis and Treatment of Lyme Disease in the United States --------------------------------------------------------------------- AUTHORS: M. H. Ziska, S. T. Donta, F. C. Demarest REFERENCE: Infection 24 (1996) No. 2, 182-186 ABSTRACT:

To assess physician preferences in the diagnosis and treatment of Lyme disease, questionnaires were sent to physicians in various Lyme disease endemic areas in the U.S. Seventy-eight responses were analyzed. Both ELISA and Western blot were ordered by 86% of responders. Fifty percent of responders believed that 25% or more of patients who have Lyme disease were seronegative. The treatment was influenced by physician specialty. Antibiotic treatment for tick bite was prescribed by 20% of responders. Erythema migrans rash was treated by all responders without serologic confirmation. The median treatment duration of erythema migrans was 4 weeks. For post-erythema migrans Lyme disease, 43% of responders treat 3 months or more; for chronic Lyme disease, 57% of responders treat 3 months or more. Our survey documents significant differences between published recommendations and actual practices. Physician education and clinical trials are needed to clarify the reasons for these differences.

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II. NIAID: NIAID Awards Contract for Post-Lyme Disease Syndrome Studies ----------------------------------------------------------------- Sender: John Bowersox <[email protected]> Office of Communications National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda, MD Friday, June 28, 1996 (301) 402-1663

The National Institute of Allergy and Infectious Diseases (NIAID) has awarded a five-year contract to the New England Medical Center (NEMC) in Boston, Mass., to study the pathogenesis and treatment of post-Lyme disease syndrome (PLDS). Mark Klempner, M.D., is the principal investigator of the $4.2 million study.

"This research will help us answer important questions regarding the nature of Lyme disease sequelae and the most effective treatment for individuals affected by this syndrome," says NIAID Director Anthony S. Fauci, M.D.

Lyme disease is caused by infection with the tick-borne spirochete Borrelia burgdorferi. Since 1982, when the organism was first identified by NIAID scientists, more than 50,000 cases of Lyme disease have been reported in the United States. Patients usually are treated successfully in the early stages of the disease with a two- to four- week course of oral antibiotics. Additional treatment with intravenous antibiotics may be required in some cases. Several months after patients with the initial symptoms of Lyme disease have been treated, some of them develop PLDS, a condition also known as chronic Lyme disease and characterized by persistent musculoskeletal and peripheral nerve pain, fatigue and memory impairment.

"There is much uncertainty about the pathogenesis of PLDS. We don't know if it is caused by ongoing active infection with B. burgdorferi or another tick-borne pathogen, or if PLDS symptoms result from reinfection," says John R. La Montagne, Ph.D., director of NIAID's Division of Microbiology and Infectious Diseases. "Inflammatory or autoimmune responses occurring during early infection, prior to treatment with antibiotics, may also play a role in PLDS. We also have a lot to learn about its clinical manifestations. This contract will allow us to define this syndrome more precisely and develop rational strategies for treating it."

As contractor, NEMC researchers will work closely with NIAID staff, and collaborate with scientists at New York Medical College, the University of Minnesota School of Medicine, and Tufts University School of Medicine. Studies on the cause or causes of PLDS and the evaluation of potential therapies for patients with PLDS are planned. Treatment success will be measured with a variety of tests that assess symptoms, signs and laboratory manifestations of PLDS.

This contract award to NEMC follows a rigorous objective review process, during which all proposals received under an NIAID solicitation were evaluated and scored by non-government Lyme disease experts. The new study further expands NIAID's growing portfolio of Lyme disease research projects. NIAID currently supports a variety of investigator-initiated studies of the pathogenesis, diagnosis and treatment of Lyme disease. In addition, intramural scientists from NIAID and other institutes at the National Institutes of Health (NIH) are collaborating on Lyme disease studies.

According to NIAID's Phillip Baker, Ph.D., the project officer for the study, the NEMC researchers will work closely with NIH intramural investigators.

"Although these new studies will not supply all the answers with regard to the etiology and treatment of PLDS," says Dr. Baker, "they should provide meaningful information that can help us move toward the development of effective solutions to this problem."

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III. NIAID: Questions and Answers About NIAID's Chronic Lyme Disease Study --------------------------------------------------------------------- Sender: Judy Murphy <[email protected]> Office of Communications National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda, MD 20892 June 1996 The National Institute of Allergy and Infectious Diseases (NIAID) recently announced the award of a five-year contract to the New England Medical Center (NEMC) to study the pathogenesis and treatment of post-Lyme disease syndrome (PLDS). Many people have called NIAID to ask questions about this contract and to voice their opinions. The question-and-answer document below is designed to respond to these concerns to the extent possible at this time.

It is important to keep in mind that this is a research study, designed to help scientists better understand Lyme disease and to develop better ways of treating this disease. The research carried out under NIAID's direction as a part of this contract will increase our knowledge of this disease and provide the foundation for new and potentially more effective approaches to be explored in future studies. The ultimate goal will be to improve the diagnosis and treatment of people with PLDS.

Q. Why is NIAID funding this study?

A. Although scientists have identified Borrelia burgdorferi as the bacterium that causes Lyme disease, we need to know much more about the pathology associated with this disease. Scientists have many questions about the chronic manifestations of Lyme disease. The issue is not whether such a syndrome exists; rather, it is how B. burgdorferi is able to elicit such a broad range of long-term problems in some people.

We don't know whether the symptoms associated with PLDS are caused by one or more of the following: an ongoing (persistent) infection with B. burgdorferi or another tick-borne pathogen; reinfection with B. burgdorferi; an autoimmune or inflammatory response associated with the initial infection; or some other yet-to-be- defined mechanism. For this reason, NIAID is using the term PLDS, rather than chronic Lyme disease. The latter implies that the symptoms observed are the result of persistent infection by B. burgdorferi. Although that indeed may be the case, in most instances direct evidence of persistent infection is lacking.

We also need to document what constitutes PLDS because the clinical characteristics of this syndrome have not been described precisely. In addition, physicians are uncertain about which treatment strategies would be most effective. For example: * What types of antibiotics should be used? * How long should they be taken? * If beneficial effects occur, how long do they last? * Should drugs other than antibiotics be tested? * What outcomes can be used to determine that a given course of antibiotic treatment is indeed effective?

Research under this contract will examine many of these questions in a step-wise and systematic manner. This will involve conducting preliminary studies to more fully characterize PLDS. The study will determine the therapeutic approaches, outcomes and monitoring techniques likely to give the most useful information and help doctors who are treating people with PLDS.

Q. Who are the investigators working on this contract?

A. Dr. Mark Klempner of the New England Medical Center is the principal investigator. Together with the NIAID project officer, Dr. Klempner is responsible for the overall design and conduct of the studies performed under the contract. Dr. Arthur Weinstein will coordinate all aspects of the study at Westchester County Medical Center/New York Medical College. Dr. Gary Wormser, also at New York Medical College, will oversee the administration of study medications. In this role, he will work closely with the nursing staff to minimize any adverse reactions to antibiotics, as well as bacterial infections sometimes associated with prolonged intravenous therapy. He also will be responsible for the culture of spinal fluid samples to detect the presence of viable B. burgdorferi. Dr. Jesse Goodman, University of Minnesota School of Medicine, will conduct all laboratory tests for the detection of possible co-infecting agents (ehrlichia and babesia). Dr. Allen Steere of Tufts University will oversee blinded serologic assays on
patient blood samples. All of these investigators are experts in their fields. Because the studies will be blinded (see below), any possible bias of investigators will be avoided.

Q. How were the contract proposals reviewed and evaluated?

A. A panel of scientists reviews and evaluates contract proposals, ranking them according to scientific merit, which is one of the chief factors considered in a contract award. Other factors include the projected cost of carrying out the work required by the contract. The contract proposal provides evidence that the investigators can meet the scientific objectives established by the Institute for carrying out the type of studies to be done under the contract. Thus, the proposal provides a means for the review panel to evaluate both the scientific expertise and the soundness of the experimental design devised by the offerors. Although the sample protocol may contain elements that are eventually adopted into the final protocol, its primary purpose is to provide a means for the scientific reviewers to assess the capability and approach of the offerors. In contrast to staff involvement with investigators given a research grant, the Institute staff work with investigators
under contract at every step to refine the design of the treatment protocol to ensure that the studies to be performed will achieve NIAID's ultimate objectives.

Q. Will clinical trials be part of this contract?

A. Yes. Phase III clinical studies are a major component. These will be multicentered studies conducted in collaboration with scientists in the intramural research program of the NIAID and elsewhere. The goal of the studies is to further characterize PLDS so that rational and more effective therapeutic approaches can be devised for use in larger populations of patients.

These studies will be double-blind and placebo-controlled. This means that all specimens to be tested will be coded so that neither the investigators nor the patients will know who is getting antibiotic and who is receiving placebo. Only after the study has been completed and all specimens have been analyzed will the codes be broken so that the effectiveness of treatment can be evaluated. Such an approach is designed to ensure objectivity and rule out any possible influence of bias or preconceived ideas about any aspect of the studies.

Protocol details still being worked out include: * the antibiotics to be tested -- which ones, in what sequence and for how long; * numbers of patients, which will be determined by the protocol design and biostatistical considerations.

Q. Who will oversee the work done under this contract?

A. The NIAID Project Officer will have final approval of all studies that will be undertaken. As with all Phase III clinical studies, an independent Data and Safety Monitoring Board (DSMB) -- appointed by the National Institutes of Health (NIH) -- will regularly evaluate the results obtained. In addition, NIAID is establishing an advisory body made up of research scientists, medical experts and members of Lyme disease patient advocacy groups to assist in defining the issues to be addressed and in resolving any problems that may arise during the course of these studies.

Q. How will studies conducted under this contract relate to the NIH intramural clinical trial?

A. NEMC researchers will work closely with NIH intramural investigators, although the patient populations selected for each study will differ. In the contract studies, patients will have had a documented case of acute Lyme disease, will have received treatment and recovered, but they will subsequently have developed all of the signs and symptoms associated with PLDS. By contrast, patients to be enrolled in the intramural studies will have a higher probability of being actively infected based on the results of a variety of laboratory tests. Although the contract studies will have a placebo arm, all patients enrolled in the intramural studies who fill certain criteria specified in the protocol will receive antibiotic.

Investigators in both studies will collaborate to determine whether the immunologic and diagnostic assays used to monitor the effectiveness of antibiotic therapy prove useful for both groups of patients. New assays not currently available to physicians will be used, and NIAID staff hope that these tests will provide valuable insights into PLDS and will prove useful in evaluating the effectiveness of antibiotic treatment.

Q. The intramural studies require a positive antibody test and Western blot. Will the contract studies also require such tests, even though some people with symptoms of PLDS are seronegative?

A. These antibody tests are used in the initial diagnosis of acute Lyme disease. Although the patients in the intramural studies must have positive ELISA and Western blot tests, the contract study patients may or may not be antibody positive if they have been treated in the past with antibiotics.

Q. When will final details of any protocols be complete?

A. We plan to be enrolling and treating patients with PLDS by early fall. The intramural study is already open to accrual. As soon as information about the studies becomes available, NIAID will post it on our home page on the World Wide Web (www.niaid.nih.gov) and alert the newsletters on our mailing list. NEMC will also publicize new developments.

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IV. AP: N.J. Gov. Has Lyme Symptoms -------------------------------------- DATE: July 23, 1996 DATELINE: TRENTON, N.J.

Gov. Christie Whitman has shown symptoms of a tick-borne blood infection that could be Lyme disease, but she is feeling well and maintaining her work schedule, her spokeswoman said Tuesday.

Whitman is on an antibiotic that is expected to clear up the infection without further illness, spokeswoman Becky Taylor said. She said the governor would probably have a blood test Tuesday in hopes of getting a definite diagnosis.

Whitman, 49, canceled her public schedule last Wednesday because she was not feeling well. Her office at the time said she had flulike symptoms.

The first-term Republican, a prominent moderate, has repeatedly said she is not interested in the party's vice presidential nomination. She had attributed fatigue and an aching elbow to her busy schedule and recurrent tendinitis and did not seek medical treatment until last week when she got a high fever and increasing body aches, the Asbury Park Press reported Tuesday.

Whitman told the newspaper Monday that her doctor suspected she got one of three illnesses spread by deer tick bites: Lyme disease, Rocky Mountain spotted fever or HGE, a bacterial infection identified last year.

The governor and her husband, John, have a farm in an area with a relatively high incidence of Lyme disease.

She said she does not recall being bitten by a tick. John Whitman recently had the bull's-eye rash associated with Lyme disease, although he did not show any other Lyme symptoms, the newspaper said.

Medical attention for Lyme disease is important, one expert said.

"It's important to make a diagnosis and get treatment. The symptoms that do not receive adequate treatment may recur," said Dr. David Alcid, chief of infectious diseases at St. Peter's Medical Center, New Brunswick.

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