Chronic Lyme disease most often
produces persistent arthritis or nervous system problems, although the
heart also can be involved. Lyme arthritis usually affects one or several
large joints, often the knee. If the central nervous system is involved,
symptoms may include headaches, nausea and vomiting, memory loss and a
variety of other cognitive, behavioral and sleep problems. Involvement
of the peripheral nerves can result in radiating pain in the limbs, numbness
and partial paralysis.
No one knows why in some patients
with late Lyme disease symptoms eventually diminish or disappear, whereas
in other patients the symptoms persist. Scientists think that in some cases
the spirochete may evade the immune system. It then survives in numbers
too low to be detected by conventional tests, yet high enough to produce
illness. Some scientists speculate that ongoing infection may even be caused
by a second tick-borne pathogen. Persistent symptoms also may be the result
of an overactive immune response that continues to injure the host?s tissues
long after the organism has been eradicated. Continued research is essential
to making progress against this disease. Since 1981, when NIAID scientists
first isolated the responsible organism, the Institute has supported an
active research program on Lyme disease. Much of this research focuses
on the pathogenesis, or disease process. This includes the study of the
biology of B. burgdorferi, how it evades the immune system, how it interacts
with its human host, its genetic components that allow the organism to
control surface protein expression, and differences in human genes that
account for the variations in the immune response among individuals.
There is no uniformity among laboratories
that perform tests to detect antibodies in the serum of the blood, contributing
to the misdiagnosis of Lyme disease. To overcome this problem, NIAID staff
met with officials of the Centers for Disease Control and Prevention (CDC)
in the fall of 1994 to discuss standardization of the Western Blot diagnostic
test. Guidelines for laboratories that perform and interpret serologic
tests were developed and a summary was published in the CDC?s Morbidity
and Mortality Weekly Report (MMWR). Further improvements in existing tests,
as well as the development of new technologies to diagnose Lyme disease
remain an Institute priority.
Since 1994, NIAID has convened meetings
to address the issues surrounding chronic Lyme disease. Attending were
scientists involved in Lyme disease at NIH and elsewhere, physicians and
patient advocates. The participants acknowledged that determining whether
chronic Lyme disease is caused by persistent infection or is a post-infectious
disorder is a major research goal. Finding the answer to this question
for any individual patient will have an important bearing on his or her
treatment. While the participants acknowledged the difficulties in carrying
out clinical trials to evaluate chronic Lyme disease, they agreed that
clinical trials are necessary to resolve questions about optimal treatment.
Participants agreed that the first
trial should focus on a well-defined patient population with probable B.
burgdorferi infection that might respond to antibiotics. Patients could
then be selected on the basis of relapse or non-response following appropriate
treatment for early-stage Lyme disease. This would provide common criteria
for studying and treating this multi-symptom disease. Such patients might
include (1) those with persistent arthritis or persistent fatigue or fibromyalgia;
(2) those with cognitive abnormalities, neuroradiculitis, headache or encephalomyelitis;
and (3) those with objective evidence of continuing B. burgdorferi infection.
The group discussed possible clinical
trial designs for assessing the effectiveness of antibiotic therapy for
the treatment of chronic Lyme disease. A Request for Proposals (RFP) reflecting
this discussion was issued to solicit proposals for conducting placebo-controlled
studies in that regard. After rigorous review of all proposals submitted,
this five-year initiative is now under way and involves several collaborating
institutions. Another closely related study also is being funded by means
of a research grant. Additionally, NIAID and other NIH scientists have
launched a separate intramural study to better characterize and treat ongoing
Lyme disease. Researchers from both studies will work closely together
with the NIAID Project Officer and under the guidance of an advisory panel
of Lyme disease scientists, medical experts, and patient representatives.
Meanwhile, NIAID continues to pursue
the underlying mechanisms of B. burgdorferi infection through grants to
study immune response to Lyme disease infection and vaccination, and contracts
to study animal models of chronic Lyme disease. These efforts will ultimately
advance our understanding of chronic Lyme disease and lay the groundwork
for future clinical trials.