Context.— The use of serologic testing to diagnose Lyme disease (LD) is a source
of controversy. Expert recommendations also discourage the routine use of
antibiotic therapy for prophylaxis of LD following tick bites, but the extent
to which physicians in endemic areas have adopted these recommendations is
not known.
Objective.— To assess the pattern of use of serologic testing and antibiotic therapy
for tick bites and LD and associated charges for management in an endemic
area.
Design.— Active surveillance of patient-physician encounters for tick bites and
LD.
Setting.— Primary care practices on the Eastern Shore of Maryland.
Patients.— Consecutive sample of 232 patients with tick bites, LD (defined by physician
diagnosis in medical record), and suspected LD (physician notation of possible,
but not definite LD) seen in 1995.
Main Outcome Measures.— Serologic testing for LD, test results, antibiotic therapy, and direct
costs of management.
Results.— Surveillance identified 142 patients (61.2%) with diagnoses of tick
bites, 40 patients (17.2%) with LD, and 50 patients (21.6%) with suspected
LD. Of the 142 patients seen for tick bites, 95 (67%) underwent serologic
testing for LD. Of these, 93 patients had initial negative or equivocal results;
24 (26%) of the 93 had convalescent testing, with 1 seroconversion. Seventy-eight
patients (55%) with a diagnosis of tick bite received antibiotic therapy.
No patients with tick bite developed clinical LD. Serologic testing for LD
was performed for 36 patients (90%) with a diagnosis of LD and 46 patients
(92%) with suspected LD. In most cases, antibiotics were prescribed before
serologic test results became available. Convalescent testing was not performed
for 37 (86%) of the 43 patients with suspected LD who had initial negative
or equivocal results. Of these 37 patients, 25 (68%) did not receive antibiotic
therapy. Direct charges for treatment of these 232 patients totaled $47595,
one third of which was attributable to serologic testing. A total of 32% of
direct charges were for patients with tick bites, 48% were for patients with
LD, and 20% were for patients with suspected LD.
Conclusions.— In this setting, most patients consulting physicians for tick bites
received prophylactic antibiotic therapy of unproven efficacy and underwent
unnecessary, costly serologic testing. Despite almost universal use in this
study, serologic testing for LD did not appear to influence treatment of patients
diagnosed as having LD.
SINCE ITS DESIGNATION as a nationally reportable disease in January
1991, Lyme disease (LD) has been by far the most commonly reported vector-borne
infectious disease in the United States.1 It
is understandably a cause for much concern among physicians and patients in
endemic areas. In the absence of erythema migrans, the diagnosis of LD is
based on clinical criteria assisted by serologic testing in patients with
characteristic clinical manifestations.
The appropriate management of patients bitten by ticks in endemic areas
has proved problematic. Although most of the literature dealing with management
of tick bites does not recommend antibiotic prophylaxis,2-5
even in highly endemic areas, a large proportion of practicing physicians
prescribe antibiotics for tick bites.6-8
Further, the use of serologic testing in the management of LD has proved a
source of confusion and controversy9-11
and has rarely been discussed in the context of tick bites. Retrospective
studies of the clinical context in which serologic testing for LD has been
performed have called into question physicians' use of these tests.12,13
The Eastern Shore of Maryland is an area endemic for LD, having the
highest incidence in the state.14 In 1995,
the incidence rate of reported LD in Kent County was 86 cases per 100000 population
and varied in the 4 adjacent counties from 14 to 64 cases per 100000 population.15 We assessed patterns of use of serologic tests and
antibiotic therapy for tick bites and LD by physicians in this rural, endemic
setting.
Patients prospectively identified with clinical diagnoses of tick bites,
LD, or suspected LD seen by primary care practitioners in Kent County, Maryland,
and within the Delmarva Health Plan (DHP) in the adjacent 4-county area on
the Eastern Shore of Maryland from January through November 1995 were included
in the study. Patients seeking medical advice following tick bites, but without
symptoms of LD, were designated as having tick bite. Cases for which the physician
recorded a diagnosis of LD in the medical record were designated as having
LD. The data used to make the diagnoses were not evaluated. Patients with
LD noted in the medical record as a possible diagnosis, but not considered
by the physician as a definite diagnosis, were designated as having suspected
LD.
Arrangements were made with the offices of primary care practitioners
to keep a roster of all patients seen with LD, suspected LD, or tick bites.
The communicable disease surveillance nurses of the Kent County Health Department
visited offices in Kent County weekly to abstract data from the medical records
of patients appearing on the rosters. A nurse made visits to the practices
in the DHP periodically in response to calls from the physicians' offices
and/or receipt of computer lists from the DHP of encounters for LD and insect
bites, or of lists of those undergoing serologic tests for LD, abstracting
data from the medical records of patients identified through these mechanisms.
The following information was extracted from the patient charts: diagnosis,
date of onset, dates and types of visits to the physician, dates of diagnostic
tests and their results, dates of procedures and their results, dates of hospitalizations,
and therapy prescribed. Charges for physician and/or hospital visits, serologic
tests, procedures, and antibiotic therapy were ascertained. For patients within
DHP, all enzyme immunoassays (EIAs) were performed in the same laboratory
using the Lyme Stat Test Kit (Whittaker Bioproducts, Walkersville, Md). Serologic
test specimens for patients in Kent County who were not members of DHP, in
addition to being sent to the above laboratory, were sent to several commercial
laboratories, each of which used a different kit. Western blot confirmation
tests for LD were performed in several commercial laboratories.
Since no patient identifiers were to be retained following the collection
of preexisting medical record information, this study received an exemption
from informed consent by the institutional review boards of the University
of Maryland at Baltimore and the Maryland Department of Health and Mental
Hygiene. Data were recorded and analysis was performed using Epi Info, version
6.16
Of a total of 270 medical records reviewed, 232 patients with diagnoses
of tick bite, LD, and suspected LD were identified: 142 (61.2%) with tick
bite, 40 (17.2%) with LD, and 50 (21.6%) with suspected LD. There was a similar
number of males and females (50.4% female). The mean age was 38.7 years, with
a range of 1 to 91 years. There was no significant difference among the 3
categories for sex or age (data not shown). Sixty-seven percent of the patients
were seen by family practitioners, 18% by internists, 12% by pediatricians,
and 3% by gynecologists. Patients were seen by 11 physicians in Kent County
and 38 physicians through the DHP in the adjacent 4 counties.
Serologic testing was performed on two thirds of the patients with tick
bite (Table 1). Three patients
(3.2%) had initially positive or equivocal EIA results. For the 93 patients
with initial negative or equivocal serologic test results, repeat specimens
were sent for 24 (Table 2), with
one of these patients demonstrating seroconversion (nonsimultaneous testing
of acute and convalescent sera). Repeat EIA testing was performed, on average,
42 days (range, 10-94 days) after initial testing. None of the patients with
tick bite had Western blot testing.
Seventy-eight patients (54.9%) seen for tick bites received prophylactic
antibiotic therapy (Table 1).
A third of patients with tick bite both underwent serologic testing and received
antibiotic therapy, with therapy initiated prior to or simultaneous with submission
of serologic specimens for 88% of the patients who were both tested and treated
(Table 3).
The majority of treated patients received either doxycycline (44.9%)
or amoxicillin (35.9%), with another 11.5% receiving oral cephalosporins,
mostly cefadroxil. The remaining 6 patients received azithromycin or ciprofloxacin
(2 each) or clarithromycin or amoxicillin with clavulanate (1 each). The mean
(SD) duration of therapy was 12.7 (3.9) days.
There were no cases of clinical LD among the patients who presented
with tick bites.
Serologic testing for LD was used more frequently in DHP than in Kent
County (94% vs 50%, respectively; P<.001), and
antibiotics were prescribed less often (40% vs 64%, respectively; corrected χ2P=.01). These differences were attributable
primarily to 4 physicians in Kent County who used serologic testing less frequently
and treated more often, although there was no characteristic pattern between
their use of serologic testing and antibiotic treatment.
Enzyme immunoassay testing was performed for approximately 90% of patients
with LD and suspected LD (Table 4
and Table 5). The results were
positive for 86% of the LD patients and 9% of the suspected LD patients.
Antibiotic therapy was prescribed for 95% of LD patients and 38% of
suspected LD patients (Table 4
and Table 5). As was the case
for patients with tick bite, this therapy was prescribed before or simultaneous
with obtaining specimens for serologic testing in most patients receiving
antibiotics (Table 3). The 2 LD
patients who did not receive antibiotic therapy had serum specimens sent within
a few days of presentation, with negative results for both. All 8 patients
who did not have serologic testing performed received antibiotic therapy (Table 4 and Table 5). Most patients with LD or suspected LD received doxycycline
(53% for both groups) or amoxicillin (29% and 37%, respectively) as initial
therapy. Five LD patients (13%) received intravenous ceftriaxone at some time
during their treatment. The manifestations of patients receiving ceftriaxone
included arthritis, facial palsy, and other neurologic symptoms. None of the
suspected LD patients received ceftriaxone.
Six patients (16.2%) had Western blot testing (5 with LD and 1 with
suspected LD) performed. All had unequivocally positive EIA results, and all
but 1 (LD diagnosis) had positive Western blot results.
Convalescent samples were not submitted for most patients with LD and
suspected LD who had initial negative or equivocal EIA results (Table 2). Two of the LD patients with negative acute test results
demonstrated seroconversion on convalescent testing. The 2 patients with a
diagnosis of LD who did not receive antibiotic therapy were among those with
a single, negative serologic test. Two thirds of the 37 suspected LD patients
with negative or equivocal, single serologic test results were not treated
with antibiotics (Table 2).
Charges Associated With LD
The total direct charges for diagnosing and managing tick bites and
LD for our 232 subjects was $47595 (Table
6). The charge for physician visits represented 35.5%, while the
charges for serologic testing for LD, antibiotic therapy, procedures, and
other medical expenses were 33.0%, 24.6%, and 6.9%, respectively. The average
direct charge per patient was $205, being the least for patients with tick
bite ($109) and the most for patients with LD ($569). Tick bites accounted
for the largest (43.0%) proportion of charges for serologic testing for LD,
43.1% of the charges for physician visits, and 32.6% of total charges. Because
of the high cost of intravenous ceftriaxone given to 5 patients with LD, LD
accounted for 84.1% of charges for antibiotics and 47.8% of the direct charges
for the 3 categories of patients.
It is not surprising that more patients were seen for tick bites than
for diagnosed or suspected LD. A previous survey of physicians in the state
showed that almost 4 times as many visits to physicians resulted from tick
bites as from diagnosed and suspected LD.7
In a different geographic region, Falco and Fish,17
identifying patients through the submission of ticks for analysis, found that
two thirds of subjects had consulted their physicians about the bite. Ley
et al,12 retrospectively identifying patients
who had serologic tests for LD performed in California, reported that one
fifth of patients had serologic specimens submitted because of tick bites.
In our study, through prospective identification of office visits, patients
with tick bites constituted not only the majority of patients seen by physicians,
but also the majority of patients for whom LD serologic testing was performed.
The 3.2% prevalence of Borrelia burgdorferi
antibodies in acute specimens in our subjects with tick bites probably represents
the background seropositivity rate and is consistent with seroprevalence rates
in other endemic areas.10 The extent of use
of serologic testing for these patients with tick bites is curious. Recommendations
regarding the use of serologic testing for tick bites have not been made,
and we are unaware of any prospective study of the use of serologic testing
for patients with tick bites. Serologic testing is unlikely to contribute
to the management of patients presenting with tick bites. Antibodies are often
not detectable until several weeks after infection, early therapy can abort
antibody response, and patients who have been infected with B burgdorferi may remain seropositive for years despite having been
treated appropriately and despite being free of disease.18-21
Serologic testing is of theoretical use when assessing for asymptomatic seroconversion
among those initially seronegative with attached, engorged ticks, but convalescent
testing was performed for only one quarter of our seronegative patients with
tick bite. The use of serologic tests makes little if any contribution to
the management of patients with tick bites and is not a small issue in light
of the associated costs.
Slightly over half the patients with tick bite received prophylactic
antibiotic therapy, results similar to those reported by Falco and Fish,17 and up to twice as frequently as reported in physician
surveys.6-8 Prophylactic
therapy for tick bites is controversial. Clinical trials have not found a
significant advantage to treatment, but, given the low rate of infection among
the untreated patients (1.1%-3.4%), the sample sizes may have been too small
to demonstrate significant differences,2-5
and the only patients in those studies with clear evidence of subsequent disease,
unequivocal seroconversion, or both were those not treated. Nonetheless, it
appears that approximately 100 patients with tick bites in areas endemic for
LD would require treatment to prevent LD in 1 or 2 patients, and most of these
could be easily identified for early treatment of LD. In light of the lack
of convincing evidence of the benefit of prophylactic therapy, it is generally
suggested that patients with tick bite exposures should be managed expectantly,2-4 especially as early
LD can be easily and effectively treated.22-24
Further, it has been suggested that, as with Rocky Mountain spotted fever,
prophylactic therapy may simply delay onset and obscure diagnosis.25 The Centers for Disease Control and Prevention (CDC)
do not recommend the routine use of prophylactic antibiotic therapy for tick
bites, but rather advise primary preventive measures backed by secondary prevention
through patient and physician education for prompt recognition of signs and
symptoms of LD.26
Prophylactic therapy may be judicious in certain circumstances,27-29 ie, in the case of
an attached, engorged tick in an endemic area, and late manifestations of
LD have been reported among patients who did not recall acute symptoms of
LD.30,31 It must be stressed,
however, that if antibiotic prophylaxis is to be given, it should be restricted
to medications of proven efficacy for LD.32
Our study suggests that physicians managing patients with tick bites
in communities with endemic disease are either unaware of recommendations
against routine prophylactic antibiotic therapy, disagree with them, or find
them infeasible in practice. Many patients on the Maryland Eastern Shore are
intensely concerned about LD and strongly desire chemoprophylaxis as well
as serologic testing for tick bites. Their physicians may simply be responding
to these patients' concerns, as indicated in our communications with these
physicians (unpublished data).
Almost all of the patients with the clinical diagnosis of LD received
antibiotic therapy, regardless of whether serologic testing was performed.
The significant difference in seropositivity between those diagnosed as having
LD and those with suspected LD (P<.001) could
simply reflect that those with a clear clinical diagnosis of LD were more
likely to have positive serologic findings, but it is also consistent with
physicians having used the results of serologic testing to categorize the
patients. Because 80% of patients with suspected LD and LD who received antibiotic
therapy were prescribed antibiotics before or simultaneous with drawing specimens
for serologic testing, serologic testing contributed to the treatment of only
a few of these patients. Performance of serologic testing for LD may have
complicated the management of the 2 patients designated as LD who had negative
serologic test results and were not treated, one of whom had a "bull's-eye
rash."
The failure to obtain convalescent serologic testing for most of the
suspected LD patients with negative initial studies is of particular interest,
especially since two thirds of this group did not receive antibiotic therapy.
If some of these untreated patients with suspected LD actually had LD, they
would be at risk for the development of late manifestations.22
The CDC and other sources have recently recommended that, in the absence
of erythema migrans, a 2-tiered approach be used in serologic testing for
LD, with initial positive or equivocal EIA results confirmed by Western blot.33-35 Only 6 of the 41
patients in our study with positive or equivocal EIA results had confirmatory
Western blot. Our data support the conclusion that many patients in endemic
areas suspected of having LD are being treated on the basis of clinical impression
and not laboratory testing, consistent with a recent physician survey.8 For patients without the characteristic clinical manifestations
of LD, especially in areas of low prevalence in which EIA has much lower positive
predictive value, confirmatory Western blot must be used to assist in making
therapeutic decisions. The use of Western blot confirmation is of particular
importance when considering expensive and potentially harmful antibiotic therapy.36 Due to the expense of ceftriaxone, LD patients accounted
for the overwhelming majority of the charges for antibiotic therapy, and antibiotic
therapy accounted for a large proportion of total direct charges for those
with LD. None of the 5 LD patients who received ceftriaxone had erythema migrans,
and only 1 underwent Western blot testing.
We believe that we captured almost all the 1995 patient encounters in
the Kent County sample and the majority of those in the DHP sample but were
unable to estimate completeness of ascertainment. If incomplete capture introduced
bias, it would most likely be in relative underreporting of cases of tick
bite and, to a lesser extent, of suspected LD. Tick bite encounters most likely
to be missed would be those for which the tick bite was a secondary issue
for the visit. For DHP patients, ascertainment would be disproportionately
high for those tick bite cases for whom serologic testing was ordered, having
used a computer-generated list of serologic testing. This may bias the estimate
of the proportion of patients with tick bite for whom serologic testing is
ordered, but could only underestimate the costs engendered by tick bites.
The clustering of patients with several physicians, primarily in Kent
County, influences the estimates for the use of serologic testing and antibiotic
therapy for tick bites among the 11 Kent County physicians, but their elimination
would not substantially alter the conclusions of the study.
In summary, we found that tick bites account for a substantial portion
of the burden of LD-related costs and patient-physician encounters. Most patients
with tick bites are undergoing costly serologic testing of no benefit, and
the majority are receiving prophylactic antibiotic therapy, an intervention
of unproven benefit. Results of serologic testing had minimal impact on the
treatment of our patients diagnosed as having LD. Increased educational efforts
among physicians regarding appropriate use of serologic testing seems warranted,
as well as anticipatory counseling of patients in endemic areas regarding
management of tick bites. In light of the extensive use of prophylactic antibiotic
therapy for tick bites, it is imperative that definitive evaluation of the
effectiveness of such therapy be performed.
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