Rheumatologist Arthur Weinstein, M.D., has two NIH grants to research why some patients continue to suffer even after treatment with antibiotics.
Arthur Weinstein, M.D., checks out Andra Sramek, who volunteered for a research study in the Division of Rheumatic Diseases and Immunology. Taking notes is Sara Guardino, research assistant.
Scientific background in immunology.
"When I came here, Lyme tests were being sent to Albany and it took four to six weeks to get results," Dr. Weinstein recalls. "I set up a lab to do testing because I saw the need--to have testing done reliably on this campus. There was an educational need, too, for rheumatology residents to see how the tests were performed and interpreted. It was also important for my clinical research experience
Dr. Weinstein was director of the Diagnostic Immunology Laboratory that did many laboratory tests in immunology including tests for lupus, connective tissue disorders and vasculitis.
Over the years, testing for Lyme has become controversial, which disturbs Dr. Weinstein. Since he was a member of the committee that developed the standards for Lyme testing--now referred to as the Dearborn criteria and used throughout the nation--he is especially perturbed when the tests are maligned as unreliable. "What is unreliable is the interpretation of results by doctors and patients," he claims. "A patient can have nine negative tests and then one positive one and the diagnosis is mistakenly confirmed...The best test would be to culture the bug, like you do for a urinary infection. But the Lyme bug is slow growing and you have to decide whether to treat or not before the culture is finished. Besides, the lab test to grow the bug is not very sensitive and too many patients have negative cultures of the skin or blood for it to be a routine test."
Dearborn criteria interpreted
It is true that in early acute Lyme disease, an antibody test may be of little value because it will read negative for the first several weeks and, in fact, may never be positive. But overall, 70 to 80 percent will have a positive test one to two months after being infected, says Dr. Weinstein, and in late Lyme arthritis, the test is virtually always positive months after the infection.
"A test usually isn't all or nothing. It is just a statistical probability of something," he insists. "A test is always evaluated as a range of normal, which includes 95 percent of people in that range. So at anytime, 5 percent can be outside the range, but not far outside, and still be normal."
Essentially a two-tier system, the Lyme tests comprise a screening analysis called ELISA, followed by the Western blot which is considered more reliable. In the ELISA test, an "alphabet soup" of proteins of the Lyme disease bug, Borrelia burgdorferi, is placed on a plastic plate with wells and a patient's serum is added. If the patient has antibodies to Lyme they will stick to the bug's proteins.
Arthur Weinstein, M.D., director of the Diagnostic Immunology Laboratory, began testing for Lyme disease in 1985. He is evaluating an ELISA test, which is confirmed by Western blot analysis, with, from left, DeLona Norton, Clincal Research Coordinator, and Lois Zentmaier, Laboratory Supervisor.
Just say Lyme
But there are more than 100 proteins in the mixture, so the test can be positive even when Lyme is not present. So diagnosis is confirmed by Western blot, where the proteins are separated out by electric current so that you can determine if the antibodies react with proteins specific to Borrelia. They can be read visually or interpreted by computer through a program that Dr. Weinstein developed with the help of a graduate student. Dr. Weinstein mentions that Western blot is not used right off the bat because, among other reasons, it is too labor intensive and expensive, as opposed to the ELISA, which is automated.
After he established the Lyme Disease Research Laboratory, Dr. Weinstein found himself increasingly drawn to Lyme despite its status as an infectious disease. As a rheumatologist, he found the complaints of lingering aches and pains too seductive to disregard.
As the Lyme disease program expanded to encompass other clinicians and basic scientists on campus, Dr. Weinstein found the time right in 1994 to apply to the NIH for a grant to study the "Pathogenesis of Lyme Induced Fibromyalgia." The first major funded study of Lyme's chronic rheumatic symptoms, the research utilized SPECT brain scans and other neurologic tests to detect abnormal blood flood. Psychiatrists performed psychological and neurocognitive examinations while biochemistry and molecular biologists used DNA probes to study whether there were active infections. And his own rheumatology department examined samples of blood and spinal fluid to measure for quantities of specific Lyme antibodies that came from the patients enrolled in the study. Analysis of the data began last spring.
Second post-Lyme study
While his fibromyalgia study was proceeding, Dr. Weinstein was awarded another NIH grant in conjunction with New England Medical Center/Tufts University School of Medicine in Boston.
A Western blot of serum from a patient with Lyme arthritis and the corresponding intensity of each band. Band positions and intensities are calculated using a computerized image analysis system developed by Krzysztof Kowal, Ph.D., and Arthur Weinstein, M.D. They conclude from their research that this analysis increases the objectivity and accuracy of Western blot interpretation for the diagnosis of Lyme arthritis.
"This is a double-blind, placebo-controlled study. Treatment will be for three months," he continues, "which is longer than usual. During the first month subjects will be prescribed intravenous ceftriaxone, followed by two months of oral doxycycline...So these patients will get both drugs or nothing."
Lots of questions
The purpose of the research is to determine whether this treatment regimen results in long-lasting improvement in patients with these chronic symptoms. "Lyme patients claim to feel better on antibiotics and relapse when they stop," says Dr. Weinstein, "but this is not typical in treating other infections. Does it mean we are not really treating an infection in post-Lyme disease syndrome, and that they are getting better from a placebo effect? Or is there really an infection, but the bugs are hiding and not reached by antibiotics, only to start growing again when the antibiotics are stopped? Or, are the antibiotics working by some different mechanism unrelated to killing bugs--say, are they just having some chemical effect on the brain?...
"I think this study will help to clarify which, if any, patients with chronic Lyme disease symptoms really have Lyme and should be treated with antibiotics long term. This result is a very important answer."
Considering his familiarity with the subject, is there a gut feeling about what he will find? In his best impartial viewpoint of a principal investigator, he replies, "I have no idea."
For questions concerning details about this study, please contact Gary Johnson in Boston at (617)-636-4893 or Delona Norton at (914)-594-4530 in Westchester County, NY or e-mail to firstname.lastname@example.org or email@example.com