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Table 1.—Use of Serologic Testing and Antibiotic Therapy for Tick Bites
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Table 2.—Convalescent Testing for Those With Negative or Equivocal Acute Serologic Test Results and Antibiotic Treatment
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Table 3.—Serologic Testing Among Those Receiving Antibiotic Treatment
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Table 4.—Use of Serologic Testing and Antibiotic Therapy for Lyme Disease
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Table 5.—Use of Serologic Testing and Antibiotic Therapy for Suspected Lyme Disease
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Table 6.—Charges (to Nearest US Dollar) of Diagnosis and Management of Lyme Disease, Suspected Lyme Disease, and Tick Bite*
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1.
CDC.  Lyme disease—United States, 1991-1992.  MMWR Morb Mortal Wkly Rep.1993;42:345-348.
2.
Costello CM, Steere AC, Pinkerton RE, Feder Jr HM. A prospective study of tick bites in an endemic area for Lyme disease.  J Infect Dis.1989;159:136-139.
3.
Shapiro ED, Gerber MA, Holabird NB.  et al.  A controlled trial of antimicrobial prophylaxis for Lyme disease after deer-tick bites.  N Engl J Med.1992;327:1769-1773.
4.
Agre F, Schwartz R. The value of early treatment of deer tick bites for the prevention of Lyme disease.  AJDC.1993;147:945-947.
5.
Warshafsky S, Nowakowski J, Nadelman RB, Kamer RS, Peterson SJ, Wormser GP. Efficacy of antibiotic prophylaxis for prevention of Lyme disease.  J Gen Intern Med.1996;11:329-333.
6.
Eppes SC, Klein JD, Caputo GM, Rose CD. Physician beliefs, attitudes, and approaches toward Lyme disease in an endemic area.  Clin Pediatr (Phila).1994;33:130-134.
7.
Coyle BS, Strickland GT, Liang YY, Pena C, McCarter R, Israel E. The public health impact of Lyme disease in Maryland.  J Infect Dis.1996;173:1260-1262.
8.
Ziska MH, Donta ST, Demarest FC. Physician preferences in the diagnosis and treatment of Lyme disease in the United States.  Infection.1996;24:182-186.
9.
Bakken LL, Case KL, Callister SM, Bourdeau NJ, Schell RF. Performance of 45 laboratories participating in a proficiency testing program for Lyme disease serology.  JAMA.1992;268:891-895.
10.
Gerber MA, Bieluch V, Levitz RE, Parry MF, Sabetta J, Schleiter G. Appropriateness of serologic tests and parenteral antibiotic therapy for patients with presumed Lyme disease.  Conn Med.1995;59:195-196.
11.
Craven RB, Quan TJ, Bailey RE.  et al.  Improved serodiagnostic testing for Lyme disease: results of a multicenter serologic evaluation.  Emerg Infect Dis.1996;2:136-140.
12.
Ley C, Le C, Olshen EM, Reingold AL. The use of serologic tests for Lyme disease in a prepaid health plan in California.  JAMA.1994;271:460-463.
13.
Nachamkin I, Riddle DL, Feldman M, Edelstein PH. Utilization of tests for Lyme disease antibody at a university hospital.  Clin Diagn Lab Immunol.1996;3:287-289.
14.
Steinberg SH, Strickland GT, Pena C, Israel E. Lyme disease surveillance in Maryland, 1992.  Ann Epidemiol.1996;6:24-29.
15.
Maryland Dept of Health and Mental Hygiene, Epidemiology and Disease Control Program.  Selected communicable diseases in Maryland in 1995.  Md Med J.1996;45:715-718.
16.
Dean AG, Dean JA, Coulombier D.  et al.  Epi Info, Version 6: A Word Processing, Database, and Statistics Program for Public Health on IBM-Compatible Microcomputers.  Atlanta, Ga: Centers for Disease Control and Prevention; 1994.
17.
Falco RC, Fish D. Ticks parasitizing humans in a Lyme disease endemic area of southern New York State.  Am J Epidemiol.1988;128:1146-1152.
18.
Dressler F, Yoshinari NH, Steere AC. The T-cell proliferative assay in the diagnosis of Lyme disease.  Ann Intern Med.1991;115:533-539.
19.
Dattwyler RJ, Volkman DJ, Luft BJ, Halperin JJ, Thomas J, Golightly MG. Seronegative Lyme disease: dissociation of specific T- and B-lymphocyte responses to Borrelia burgdorferi N Engl J Med.1988;319:1441-1446.
20.
Feder Jr HM, Gerber MA, Luger SW, Ryan RW. Persistence of serum antibodies to Borrelia burgdorferi in patients treated for Lyme disease.  Clin Infect Dis.1992;15:788-793.
21.
Aguero-Rosenfeld ME, Nowakowski J, Bittker S, Cooper D, Nadelman RB, Wormser GP. Evolution of the serologic response to Borrelia burgdorferi in treated patients with culture-confirmed erythema migrans.  J Clin Microbiol.1996;34:1-9.
22.
Steere AC, Hutchinson GJ, Rahn DW.  et al.  Treatment of the early manifestations of Lyme disease.  Ann Intern Med.1983;99:22-26.
23.
Dattwyler RJ, Volkman DJ, Conaty SM, Platkin SP, Luft BJ. Amoxycillin plus probenecid versus doxycycline for erythema migrans borreliosis.  Lancet.1990;336:1404-1406.
24.
Gerber MA, Shapiro ED, Burke GS, Parcells VJ, Bell GL. Lyme disease in children in southeastern Connecticut: Pediatric Lyme Disease Study Group.  N Engl J Med.1996;335:1270-1274.
25.
Nadelman RD, Nowakowski J, Wormser GP. Can Lyme borreliosis be prevented after tick bite?  Lancet.1993;342:1052.
26.
 Antibiotic prophylaxis of Lyme disease following recognized bite: Bacterial Zoonoses Branch, Division of Vector-Borne Diseases National Center for Infectious Diseases, Centers for Disease Control.  Conn Med.1991;55:691-693.
27.
Wormser GP. Lyme disease: insights into the use of antimicrobials for prevention and treatment in the context of experience with other spirochetal infections.  Mt Sinai J Med.1995;62:188-195.
28.
Magid D, Schwartz B, Craft J, Schwartz JS. Prevention of Lyme disease after tick bites: a cost-effectiveness analysis.  N Engl J Med.1992;327:534-541.
29.
Sood SK, Salzman MB, Johnson BJ.  et al.  Duration of tick attachment as a predictor of the risk of Lyme disease in an area in which Lyme disease is endemic.  J Infect Dis.1997;175:996-999.
30.
Steere AC, Taylor E, Wilson ML, Levine JF, Spielman A. Longitudinal assessment of the clinical and epidemiological features of Lyme disease in a defined population.  J Infect Dis.1986;154:295-300.
31.
Bingham PM, Galetta SL, Athreya B, Sladky J. Neurologic manifestations in children with Lyme disease.  Pediatrics.1995;96:1053-1056.
32.
Nocton JJ, Steere AC. Lyme disease.  Adv Intern Med.1995;40:69-117.
33.
CDC.  Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease.  MMWR Morb Mortal Wkly Rep.1995;44:590-591.
34.
Dressler F, Whalen JA, Reinhardt BN, Steere AC. Western blotting in the serodiagnosis of Lyme disease.  J Infect Dis.1993;167:392-400.
35.
Johnson BJB, Robbins KE, Bailey RE.  et al.  Serodiagnosis of Lyme disease: accuracy of a two-step approach using a flagella-based ELISA and immunoblotting.  J Infect Dis.1996;174:346-353.
36.
Ettestad PJ, Campbell GL, Welbel SF.  et al.  Biliary complications in the treatment of unsubstantiated Lyme disease.  J Infect Dis.1995;171:356-361.
Original Contribution
January 21, 1998

Tick Bites and Lyme Disease in an Endemic SettingProblematic Use of Serologic Testing and Prophylactic Antibiotic Therapy

Author Affiliations

From the Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, Md (Drs Fix and Strickland), and the Kent County Health Department, Chestertown, Md (Dr Grant).

JAMA. 1998;279(3):206-210. doi:10.1001/jama.279.3.206
Context.—

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,25 even in highly endemic areas, a large proportion of practicing physicians prescribe antibiotics for tick bites.68 Further, the use of serologic testing in the management of LD has proved a source of confusion and controversy911 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.

METHODS

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

RESULTS

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.

Tick Bite

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.

LD and Suspected LD

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.

COMMENT
Tick Bite

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.1821 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.68 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,25 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,24 especially as early LD can be easily and effectively treated.2224 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,2729 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).

LD and Suspected LD

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.3335 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.

Limitations

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.

Conclusion

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.

References
1.
CDC.  Lyme disease—United States, 1991-1992.  MMWR Morb Mortal Wkly Rep.1993;42:345-348.
2.
Costello CM, Steere AC, Pinkerton RE, Feder Jr HM. A prospective study of tick bites in an endemic area for Lyme disease.  J Infect Dis.1989;159:136-139.
3.
Shapiro ED, Gerber MA, Holabird NB.  et al.  A controlled trial of antimicrobial prophylaxis for Lyme disease after deer-tick bites.  N Engl J Med.1992;327:1769-1773.
4.
Agre F, Schwartz R. The value of early treatment of deer tick bites for the prevention of Lyme disease.  AJDC.1993;147:945-947.
5.
Warshafsky S, Nowakowski J, Nadelman RB, Kamer RS, Peterson SJ, Wormser GP. Efficacy of antibiotic prophylaxis for prevention of Lyme disease.  J Gen Intern Med.1996;11:329-333.
6.
Eppes SC, Klein JD, Caputo GM, Rose CD. Physician beliefs, attitudes, and approaches toward Lyme disease in an endemic area.  Clin Pediatr (Phila).1994;33:130-134.
7.
Coyle BS, Strickland GT, Liang YY, Pena C, McCarter R, Israel E. The public health impact of Lyme disease in Maryland.  J Infect Dis.1996;173:1260-1262.
8.
Ziska MH, Donta ST, Demarest FC. Physician preferences in the diagnosis and treatment of Lyme disease in the United States.  Infection.1996;24:182-186.
9.
Bakken LL, Case KL, Callister SM, Bourdeau NJ, Schell RF. Performance of 45 laboratories participating in a proficiency testing program for Lyme disease serology.  JAMA.1992;268:891-895.
10.
Gerber MA, Bieluch V, Levitz RE, Parry MF, Sabetta J, Schleiter G. Appropriateness of serologic tests and parenteral antibiotic therapy for patients with presumed Lyme disease.  Conn Med.1995;59:195-196.
11.
Craven RB, Quan TJ, Bailey RE.  et al.  Improved serodiagnostic testing for Lyme disease: results of a multicenter serologic evaluation.  Emerg Infect Dis.1996;2:136-140.
12.
Ley C, Le C, Olshen EM, Reingold AL. The use of serologic tests for Lyme disease in a prepaid health plan in California.  JAMA.1994;271:460-463.
13.
Nachamkin I, Riddle DL, Feldman M, Edelstein PH. Utilization of tests for Lyme disease antibody at a university hospital.  Clin Diagn Lab Immunol.1996;3:287-289.
14.
Steinberg SH, Strickland GT, Pena C, Israel E. Lyme disease surveillance in Maryland, 1992.  Ann Epidemiol.1996;6:24-29.
15.
Maryland Dept of Health and Mental Hygiene, Epidemiology and Disease Control Program.  Selected communicable diseases in Maryland in 1995.  Md Med J.1996;45:715-718.
16.
Dean AG, Dean JA, Coulombier D.  et al.  Epi Info, Version 6: A Word Processing, Database, and Statistics Program for Public Health on IBM-Compatible Microcomputers.  Atlanta, Ga: Centers for Disease Control and Prevention; 1994.
17.
Falco RC, Fish D. Ticks parasitizing humans in a Lyme disease endemic area of southern New York State.  Am J Epidemiol.1988;128:1146-1152.
18.
Dressler F, Yoshinari NH, Steere AC. The T-cell proliferative assay in the diagnosis of Lyme disease.  Ann Intern Med.1991;115:533-539.
19.
Dattwyler RJ, Volkman DJ, Luft BJ, Halperin JJ, Thomas J, Golightly MG. Seronegative Lyme disease: dissociation of specific T- and B-lymphocyte responses to Borrelia burgdorferi N Engl J Med.1988;319:1441-1446.
20.
Feder Jr HM, Gerber MA, Luger SW, Ryan RW. Persistence of serum antibodies to Borrelia burgdorferi in patients treated for Lyme disease.  Clin Infect Dis.1992;15:788-793.
21.
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