Long-term Outcomes of Persons With Lyme Disease
JAMA, Vol. 283, No. 5, 2 February 2000
[NOTE:  The following link is not avaiable as of 19 Nov 2000]
http://jama.ama-assn.org/issues/v283n5/full/joc90967.html

[Author Information]  Elyse G. Seltzer, MD;
Michael A. Gerber, MD; Matthew L. Cartter, MD;
Kimberly Freudigman, PhD; Eugene D. Shapiro, MD

Context  Few data exist about the long-term
outcomes of patients with Lyme disease.

Objective  To assess the long-term outcomes of
patients with Lyme disease.

Design  Two-part project including a
community-based longitudinal cohort study and a
matched cohort study.

Setting and Participants  Six hundred
seventy-eight patients identified from a random
sample of all reports of Connecticut residents
with suspected Lyme disease submitted to the
Connecticut Department of Public Health from
1984-1991 were evaluated in the longitudinal
study; for a random subsample of 212 patients from
the larger study, 212 age-matched controls without
Lyme disease also were enrolled.

Main Outcome Measures  Self-reports or parents'
reports of symptoms and ability to perform certain
daily activities since diagnosis of Lyme disease;
scores on the 36-Item Short-Form Health Survey and
the Center for Epidemiologic Studies-Depression
scale, for adults, by case-definition status and
between patients and controls.

Results  Of the 678 patients, 51.6% were female,
34.4% were children, and 64.3% met the national
surveillance case definition for Lyme disease.
Most patients (85.6%) were treated with
antimicrobial agents. Interviews were conducted a
median of 51 months after diagnosis (range, 15-135
months). An increased frequency of symptoms (eg,
pain, fatigue) or of difficulty with daily
activities (eg, performing housework, exercising)
was reported by 69% of the patients, although few
(19%) of these problems were attributed to Lyme
disease. Whenever there was a statistically
significant difference in the frequencies of
either increased symptoms or increased
difficulties with typical activities between those
who did or did not meet the surveillance case
definition, in all instances the greater frequency
of problems was in the group that did not meet the
case definition. The frequencies of reports of
both increased symptoms and increased difficulties
with typical activities among patients who had
been diagnosed as having Lyme disease were similar
to those among age-matched controls without Lyme
disease.

Conclusions  In this cohort, although many
patients reported increases in symptoms and/or
increased difficulties with typical daily
activities between 1 and 11 years after diagnosis
of Lyme disease, the frequencies of these reports
were similar to the frequencies of such reports
among age-matched controls without Lyme disease.

JAMA. 2000;283:609-616

[JOC90967]

Although Lyme disease is the most common
vector-borne illness in the United States,1 there
are few data about the long-term outcomes of
patients treated for it. Reports have appeared in
both the lay press and the medical literature of
persons who were diagnosed as having Lyme disease
and subsequently developed either recurrent or
persistent, nonspecific symptoms (such as fatigue
or arthralgia) attributed to Lyme disease
(sometimes even if they were treated with
antimicrobial therapies).2-5 Such patients
occasionally receive either repeated or prolonged
parenteral courses of antimicrobial therapy
despite statements by the American College of
Rheumatology, the Infectious Diseases Society of
America, and others that such treatment is not
warranted.6, 7 Some of these reports are about
highly selected samples of patients, many of whom
developed symptoms months to years before Lyme
disease was diagnosed and were not treated from
months to years after the onset of their
symptoms.8, 9 These patients are not comparable to
most patients who currently are being diagnosed as
having Lyme disease and being treated for it.

In both 1984 and 1985, the Connecticut State
Department of Public Health offered to test, free
of charge, serum samples of patients suspected of
having Lyme disease for antibodies against
Borrelia burgdorferi if the practitioner would
submit information about the patient.10 Since
1987, all cases of Lyme disease in Connecticut are
required to be reported to the Department of
Public Health. To assess the long-term outcomes of
patients diagnosed as having Lyme disease, we
conducted a 2-part study: a community-based,
longitudinal cohort study of a random sample of
persons with Lyme disease from approximately 1 to
11 years earlier, reported to the Connecticut
Department of Public Health, and a matched cohort
study in which the outcomes of a randomly selected
subsample of the patients reported to have had
Lyme disease from the larger study were compared
with those of controls without Lyme disease,
matched to the patients by age and area of
residence.

METHODS
[Image]

Selection of Patients for the Longitudinal Cohort
Study

From all reports submitted to the Connecticut
State Department of Public Health from 1984
through 1991 of patients with suspected Lyme
disease, a random sample (identified with the use
of a table of random numbers) was selected. If a
physician submitted a report to the Department of
Public Health, she or he was contacted and asked
for permission to contact the patient. If the
physician consented, potential patients were
contacted by telephone, and informed consent to
participate in the study was obtained. Patients
were excluded if they reported that they had never
had Lyme disease, if they did not speak English,
or if they resided outside of Connecticut at the
time of diagnosis of Lyme disease.

Selection of Patients and Controls for the Matched
Cohort Study

A random subsample of patients enrolled in the
longitudinal cohort study was selected using a
table of random numbers. For each patient in the
subsample, 1 control without a history of Lyme
disease, matched for age and area of residence,
was identified by sequential-digit dialing.11
Controls without Lyme disease were matched to
patients reported to have had Lyme disease (by age
[Image]1 year for those younger than 2 years,
[Image]2 years for those aged 2 to 10 years,
[Image]3 years for those aged 11 to 17 years, and
[Image]5 years for those aged 18 years or older).
Each telephone number was called 3 times before
advancing to the next number: once during the
daytime, once during the evening, and once during
the weekend. Respondents at telephone numbers that
were not residences, those who did not speak
English, and those who said they had been
diagnosed as having Lyme disease were excluded.

Interviews

Both patients and controls were interviewed via
telephone. If the subject was a child, a parent
was interviewed. Interviews were conducted by a
trained research assistant who used a standardized
questionnaire. Patients were asked whether they
believed they were cured of Lyme disease, whether
they experienced increased frequency of certain
symptoms, and whether they noted increased
difficulty in their abilities to perform certain
typical daily activities since being diagnosed as
having Lyme disease. For example, they were asked:
"Since you were diagnosed with Lyme disease, have
you experienced episodes of joint pain more
frequently, less frequently, or with no change in
frequency?" In addition, the Medical Outcomes
Study 36-Item Short-Form Health Survey (SF-36),12
a standardized survey that measures health-related
quality of life, and the Center for Epidemiologic
Studies-Depression (CES-D) questionnaire13
(developed for use in studies of the epidemiology
of depression in the general population) were
administered only to adults (persons aged
[Image]18 years).

All patients were asked about medical problems in
the following manner: "Do you have any medical
problems? Specifically, do you have any problems
with heart disease, kidney disease, liver disease,
etc." Controls were asked the same questions,
except questions that directly related to having
had Lyme disease in the past. Instead of asking
controls about changes in either symptoms or
difficulties with typical daily activities since
they were diagnosed as having Lyme disease,
controls were asked about changes during the same
time interval as the matched patient with Lyme
disease (eg, "During the past 5 years, have you
experienced episodes of joint pain more
frequently, less frequently, or with no change in
frequency?").

Review of Medical Records

Medical records of each patient, from as early as
1975 to the most recent visit, were reviewed by
research assistants. Information was recorded
about clinical and laboratory data at the time of
diagnosis of Lyme disease, about the treatment for
Lyme disease, and about office visits,
hospitalizations, and underlying medical
conditions both before and after the onset of Lyme
disease. Records of the reporting physician and of
any other physicians who treated the patient for
Lyme disease were reviewed. Although occasionally
there were discrepancies between a patient's
reports in the interview and the medical records,
the results were not significantly different
regardless of which data we used.

This study was approved by the human investigation
committees of the Yale School of Medicine and the
Connecticut State Department of Public Health.

Classification of Patients With Lyme Disease

An abstract of the clinical and laboratory
information at the time of diagnosis of each
patient reported to have had Lyme disease was
prepared by research assistants who were blinded
to the long-term outcomes of the patients. These
forms were reviewed by investigators who also were
blinded to the outcomes. Patients were classified
by the stage of Lyme disease at the time of
diagnosis and by whether they met the national
surveillance case definition for Lyme disease of
the Centers for Disease Control and Prevention.14
This classification was made independent of the
classification done by the health department at
the time of the report and was based on additional
information gathered for this study.

Patients with a single erythema migrans lesion at
least 5 cm in diameter (with or without concurrent
symptoms of fever, malaise, or arthralgia) that
was documented by a physician were classified as
having early localized disease. Because there were
no significant differences in the results if they
were excluded from the analyses or were included
with the cohort of patients who did not meet the
case definition, 98 patients who had an erythema
migrans rash the size of which was not documented
by a physician or was not at least 5 cm in
diameter were included in the cohort of patients
with early localized disease who met the case
definition. Patients with multiple erythema
migrans lesions were classified as having early
disseminated Lyme disease. Patients with either
early neurologic disease (eg, cranial nerve palsy,
aseptic meningitis, peripheral neuropathy) or
cardiac disease (eg, acute atrioventricular block)
and serologic evidence of infection with B
burgdorferi (a positive test result as defined by
the laboratory that did the test; confirmation by
Western immunoblot was not required) also were
classified as having early disseminated Lyme
disease. Patients with arthritis, encephalopathy,
or polyneuropathy and serologic evidence of
infection with B burgdorferi were classified as
having late-stage Lyme disease. Patients who had
only nonspecific symptoms (eg, arthralgia,
fatigue), with or without serologic evidence of
infection with B burgdorferi, and patients who had
objective signs consistent with Lyme disease other
than erythema migrans (eg, arthritis) but with no
serologic evidence of infection with B
burgdorferi, were classified as not meeting the
surveillance case definition for Lyme disease.

Statistical Methods

The data were analyzed using standard statistical
techniques. The 95% confidence intervals (CIs) for
proportions were calculated using statistical
software.15 Relative risks (RRs), associated 95%
CIs, and their statistical significance also were
calculated.16 Logistic regression was used to
adjust RRs for the effects of potential
confounders (results reported are unadjusted,
except where noted).17 All P values are 2-tailed.

RESULTS
[Image]

Longitudinal Cohort Study

A random sample of 1325 patients (15%) reported as
having Lyme disease was selected from the 8764
reports of Lyme disease received by the health
department from 1984 through 1991. Of these, 16
were not contacted at the request of the reporting
physician, 17 were deceased, 80 refused to
participate, 82 reported that they had never had
Lyme disease, 85 lived outside of Connecticut at
the time of diagnosis, and 367 could not be
located (for most of these, addresses were not
available from the report form or from the
physician or the laboratory that submitted the
report). The remaining 678 patients (median age,
36 years) were enrolled in the study. The median
age of the 445 adults was 46 years (range, 18-86
years) and of the 233 children was 8 years (range,
6 months to 17 years). There were 350 females
(51.6%) and 670 whites (98.8%). The median time
from the diagnosis of Lyme disease to the
follow-up interview was 51 months (range, 15-135
months). The signs and symptoms of the patients at
the time they presented to the reporting
physician, stratified by age and by whether they
met the surveillance case definition for Lyme
disease, are shown in Table 1.

Of the 678 patients, 70.9% (95% CI, 67.3%-74.3%)
believed they were cured of Lyme disease, 9.0%
(95% CI, 7.0%-11.4%) believed they were not cured,
and 20.1% (95% CI, 17.1%-23.3%) were unsure
whether they were cured of Lyme disease. Most
patients who reported that they were unsure if
they were cured said they were unsure whether Lyme
disease was curable. Patients who believed they
were cured of Lyme disease were less likely to
have underlying comorbid illnesses than were
patients who believed they were not cured of Lyme
disease (32% vs 46%; RR, 0.69; 95% CI, 0.51-0.94;
P = .04). Fifteen percent of adults and 5% of
children believed they were not cured of Lyme
disease (RR, 3.0; 95% CI, 1.5-5.7; P<.001).
Patients who met the surveillance case definition
for Lyme disease were more likely to believe that
they were cured of Lyme disease than were patients
who did not meet the case definition (75% vs 63%;
RR, 1.2; 95% CI, 1.1-1.3; P = .001).

Reported Increases in Symptoms and in Difficulties
With Typical Daily Activities
The proportions of patients that reported
increases in symptoms and in difficulties with
typical daily activities are shown in Table 2 and
Table 3, respectively. The proportions of patients
that attributed these increases to Lyme disease
also are shown. Overall, 31% of patients reported
no increases either in symptoms or in difficulty
with typical daily activities since having Lyme
disease, 16% reported increases either in symptoms
or in difficulties with typical activities in 1
category, 10% reported increases in 2 categories,
9% reported increases in 3 categories, 7% reported
increases in 4 categories, and 27% reported
increases in 5 or more categories. However,
overall, only 19% of the increases either in
symptoms or in difficulties with typical daily
activities were attributed to Lyme disease; most
patients attributed the increases either to aging
or to a comorbid illness, such as a stroke. There
was a statistically significant association
between whether patients believed they were not
cured of Lyme disease and increases in symptoms or
in difficulties with typical daily activities for
each of the categories reported.

The proportions of patients that reported
increases in symptoms and in difficulties with
typical daily activities, stratified by whether
they met the surveillance case definition for Lyme
disease, are also shown in Table 2 and Table 3,
respectively. In all instances in which there were
statistically significant differences between
those who did and those who did not meet the
surveillance case definition, the higher
proportion of reported problems was in the group
who did not meet the surveillance case definition.
Among the patients who did not meet the
surveillance case definition for Lyme disease and
presented with only nonspecific symptoms, there
was no significant difference in the reported
frequencies of any specific symptom, of difficulty
with any typical daily activity, or of whether
they believed they were cured of Lyme disease when
they were stratified by whether they had test
results positive for antibodies to B burgdorferi.
If the results for the categories reported in
Table 2 are summed and then averaged, there is a
statistically significant linear trend in the
proportion of patients who believed they were not
cured (patients who were unsure whether they were
cured of Lyme disease were excluded) after
stratification by whether they met the case
definition: patients who met the case definition
and did not report increased symptoms (5.9%),
patients who did not meet the case definition and
did not report increased symptoms (10.4%),
patients who met the case definition and reported
increased symptoms (26.4%), and patients who did
not meet the case definition and reported
increased symptoms (34.6%) (P<.001). A similar
trend was found among the categories reported in
Table 3: patients who met the case definition and
did not report increased difficulties with typical
daily activities (8.1%), patients who did not meet
the case definition and did not report increased
difficulties with typical daily activities
(11.1%), patients who met the case definition and
reported increased difficulties with typical daily
activities (26.6%), and patients who did not meet
the case definition and reported increased
difficulties with typical daily activities (42.4%)
(P<.001).

Antimicrobial Treatment
Overall, 85.6% of patients were treated with
antimicrobial agents for Lyme disease, 6.7% were
not treated, and for 7.7% the data on
antimicrobial therapy were unavailable. Among
subjects for whom information about treatment was
available, the proportions of adults and of
children who had received antimicrobial treatment
were similar (93% vs 91%; RR, 1.1; 95% CI,
0.9-1.4; P = .41). The frequencies of reports of
any increased symptom or increased difficulty with
a typical daily activity were similar when
patients were stratified by whether they had
received antimicrobial therapy, except for the
category of joint or muscle aches (32% of those
who had received antimicrobial therapy vs 48% of
those who had not; RR, 0.7; 95% CI, 0.5-0.9; P =
.04). The proportions of patients who received
antimicrobial treatment were similar among
patients who did and did not believe they were
cured of Lyme disease (93% vs 90%; RR, 1.04; 95%
CI, 0.95-1.1; P = .54). Patients who met the
surveillance case definition for Lyme disease were
more likely to have received antimicrobial therapy
for Lyme disease than were subjects who did not
meet the surveillance case definition (98% vs 82%;
RR, 1.2; 95% CI, 1.1-1.3; P<.001).

Differences Between Adults and Children
A higher proportion of children than of adults met
the surveillance case definition for Lyme disease
(71.7% vs 60.5%; RR, 1.2; 95% CI, 1.1-1.3;
P<.005). Adult patients were more likely to report
increased frequencies of every symptom since being
diagnosed as having Lyme disease than were
children (eg, numbness [RR, 6.6; 95% CI, 3.5-12.3;
P<.001] or memory problems [RR, 5.3; 95% CI,
3.0-9.2; P<.001]). Likewise, the proportion of
adult patients that reported increased
difficulties with each activity was significantly
higher than the proportion of children (eg,
exercise [21.1% vs 5.2%; RR, 4.1; 95% CI, 2.3-7.3;
P<.001], falling asleep [9.7% vs 4.7%; RR, 2.0;
95% CI, 1.1-3.9; P = .02], and ability to
formulate ideas [10.8% vs 3.0%; RR, 3.6; 95% CI,
1.7-7.8; P<.001]).

Results of Standardized Tests
The results of the SF-36 survey are shown in Table
4 (the optimal score in each category is 100%).
Except for the category "bodily pain," the mean
scores of patients who did and did not meet the
surveillance case definition for Lyme disease were
similar. The mean scores on the CES-D scale among
patients who did and did not meet the surveillance
case definition for Lyme disease also were similar
(Table 4). Although a higher proportion of
patients who did not meet the case definition had
scores of at least 16 (a score [Image]16 on the
CES-D questionnaire suggests that the subject
experiences depression), the difference was not
statistically significant (RR, 1.7; 95% CI,
0.97-2.8; P = .06). When patients who had
presented with only nonspecific symptoms were
stratified by whether they had positive serologic
test results for antibodies to B burgdorferi, the
mean scores for the groups were similar on both
the SF-36 and the CES-D scale.

Matched Cohort Study

Controls without a history of Lyme disease were
selected for 212 randomly selected patients
diagnosed as having Lyme disease. Using
sequential-digit dialing, 2731 telephone numbers
were called to enroll the 212 age-matched
controls. Of the numbers called, there were no
eligible persons at 1588 numbers, there was no
answer or the line was busy on 3 separate attempts
at 705 numbers, the respondent refused at 205
numbers, the respondent did not speak English at
18 numbers, and there was no adult available to
give consent at 3 numbers.

Of the 212 patients diagnosed as having Lyme
disease, 151 were adults (median age, 45 years)
and 61 were children (median age, 8 years); 59%
met the surveillance case definition for Lyme
disease. Patients and controls were similar with
respect to race and frequency of underlying
illnesses. A higher proportion of controls than of
patients was female (66% vs 49%; P<.001). The
proportions of patients and controls who reported
increased symptoms and/or increased difficulties
with typical daily activities are shown in Table
5. Although many patients who had been diagnosed
as having Lyme disease reported increased symptoms
or increased difficulties with typical daily
activities, the proportions were similar to those
reported by the matched controls, except that
there were statistically significant differences
between the groups in the categories of "joint or
muscle pain" and "ability formulating ideas."
Likewise, there were no significant differences in
the entire cohort between the cases and the
controls in the results of the SF-36 or the CES-D.
The results of these tests for the 88 adults who
met the surveillance case definition for Lyme
disease and for their matched controls are shown
in Table 6. There were no significant differences
in any of the results when conditional logistic
regression was used to adjust for differences in
potential confounders such as sex, race, and the
presence of 1 or more underlying comorbid
illnesses.

COMMENT
[Image]

Only 64% of the patients met the surveillance case
definition for Lyme disease. Among the patients
who met the definition, 88.3% presented with
either single or multiple erythema migrans. This
is similar to the proportions of patients with
single or multiple erythema migrans in other
reports of community-based, prospective studies of
Lyme disease and supports the validity of how our
patients were classified.18-20

There has been a great deal of controversy about
the consequences of infection with B burgdorferi.
Some patient advocacy groups and physicians
believe that Lyme disease is a very serious and
difficult-to-treat illness. Others believe that
the majority of patients with Lyme disease remain
relatively healthy, regardless of the stage of the
illness at the time they present, and suggest that
in many of the patients who have either persistent
or recurrent subjective complaints, Lyme disease
either was a misdiagnosis or was not the cause of
the symptoms.2-5, 18, 21-30

Our data indicate that the outcomes of most
persons diagnosed as having Lyme disease who are
treated with antimicrobial agents are excellent.
Although at the follow-up interview (a median of
51 months after diagnosis of Lyme disease) many of
the patients diagnosed as having Lyme disease
reported increased frequencies of some symptoms,
increased difficulties with typical daily
activities, or both, relatively few of the
patients attributed these problems to Lyme
disease. Moreover, the frequencies of such
complaints among patients since the diagnosis of
Lyme disease were similar to those of controls
(when asked about changes during the same period)
who had been matched to the patients by age and
area of residence. Among adults reported to have
had Lyme disease, scores on standardized tests of
health-related quality of life and on the CES-D
scale were similar to those of other generally
healthy populations, and in the matched cohort
study, among adults who met the surveillance case
definition for Lyme disease, the scores on these
standardized tests were similar to the scores of
matched controls.

Among the patients reported to have had Lyme
disease who did not meet the surveillance case
definition, three quarters had only nonspecific
symptoms (such as fatigue, arthralgia, or
headache). In these patients, the diagnosis was
based primarily on positive serologic test
results. Because of the poor specificity of
serologic tests and the low probability that a
patient with only nonspecific symptoms has Lyme
disease, it is likely that the diagnosis of Lyme
disease was inaccurate in many of these
patients.31-36 The frequencies of reported
increases in symptoms and of increased
difficulties with typical daily activities were
consistently lower (statistically significantly
lower in a number of specific categories) among
the patients who met the surveillance case
definition for Lyme disease than among those who
did not meet this case definition. In the matched
cohort study, even though patients who did not
meet the case definition were included, there were
few significant differences between the patients
and matched controls in reported increases in
symptoms or in difficulties with typical
activities. Patients did report increased joint or
muscle pain and difficulties in their abilities to
formulate ideas more frequently than did matched
controls. However, the magnitude of these
        differences was relatively small, and if a
correction in the P value considered to be
statistically significant had been made to
compensate for the effect of making multiple
comparisons (the more comparisons made, the
greater the likelihood that, by chance alone, 1 or
more of them will be statistically significant),
these differences would not be statistically
significant.37 Moreover, it is likely that there
is some degree of reporting bias that occurs after
a patient is diagnosed as having Lyme disease (ie,
patients who have been told they have Lyme disease
may be more likely than the general population to
report minor joint or muscle pains).

This study has some potential limitations.
Although the controls reported that they had not
had Lyme disease, we did not confirm this
serologically. However, the prevalence of
seropositivity in the general population of the
area is relatively low (<5%), so that it is
unlikely that the results of the study would be
significantly affected by misclassification as a
control of someone who previously had been
infected with B burgdorferi.38 Moreover, the
significance of asymptomatic infection with B
burgdorferi is unknown. We were unable to enroll a
substantial number of the potential patients who
had been randomly selected from among all patients
who had been reported to the Connecticut
Department of Public Health. However, in most
instances we were unable to contact the patients
because the report form did not have adequate
contact information available. It is unlikely that
this introduced a systematic bias into the study.
Finally, we relied on reports from patients (or
their parents, in the case of children); we did
not examine the patients. However, we did
carefully review the medical records and reported
functional outcomes of all patients to confirm
their reports. Moreover, the results of the SF-36
were consistent with our other results that
indicated that outcomes of patients reported to
have had Lyme disease generally are excellent. The
results of a recently published study of the
outcomes of persons on Nantucket Island who
previously were treated for Lyme disease are
similar to ours.39 This study does not indicate
that all patients with Lyme disease have favorable
outcomes. Indeed, there is good evidence that in
rare instances they may experience
complications—particularly recurrent arthritis in
patients who are not treated promptly and who have
a genetic predisposition to develop an
autoimmune-mediated arthritis.40-42 However, the
large size of our sample and the generally
excellent overall outcomes of the patients should
reassure both patients and physicians that the
prognosis for most patients with Lyme disease who
receive conventional antimicrobial treatment is
excellent.

Author/Article Information
[Image]

Author Affiliations: Departments of Medicine (Dr
Seltzer), Pediatrics (Drs Seltzer, Freudigman, and
Shapiro), and Epidemiology and Public Health, and
the Children's Clinical Research Center (Dr
Shapiro), Yale University School of Medicine, New
Haven, Conn; Department of Pediatrics, University
of Connecticut School of Medicine, Farmington (Dr
Gerber); and the Connecticut Department of Public
Health, Hartford (Dr Cartter). Dr Seltzer is now
with SmithKline Beecham Pharmaceuticals.

Corresponding Author: Eugene D. Shapiro, MD,
Department of Pediatrics, Yale University School
of Medicine, 333 Cedar St, New Haven, CT
06520-8064.

Funding/Support: This study was supported in part
by a grant from the Patrick and Catherine Weldon
Donaghue Medical Research Foundation.

Acknowledgment: We are grateful to Nancy Holabird,
BS, LPN, and Valerie Parcells, RN, for conducting
interviews and collecting data, to Ann Gottwals
for assisting with preparation of the article, and
to James Hadler, MD, for reviewing the article.

Financial Disclosure: Dr Shapiro has received
research support and consulted for Pasteur Mérieux
Connaught Laboratories and has given lectures that
have been supported by Glaxo-Wellcome and by
SmithKline Beecham. These companies manufacture
products to prevent or to treat Lyme disease.

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