Lyme vaccine: issues and controversies.

The development of an effective vaccine for Lyme disease represents a major advance in the control of the most prevalent vector-borne disease in the United States. It has a definite place in the total approach to control of this disease. Its use should be restricted to individuals who are at moderate to high risk of exposure to infected vector ticks. Vaccinated individuals should not be complacent about other personal protection measures, because the vaccine is not uniformly effective and protective antibody levels decay rapidly. Booster doses will be necessary, but the intervals have not yet been determined. There is a theoretical concern about the possible induction of inflammatory arthritis through an autoimmune mechanism, but there is no evidence that this condition has clinical relevance. The impact of the current lawsuits on vaccine recommendations and use remains to be determined. Continued surveillance for rare long-term side effects should address the medical risk issue. Alternative primary vaccine administration schedules are currently under study, and could lead to regimens permitting achievement of protective immunity in 6 months or less. Vaccine is not approved for use in children under the age of 15 years.

Solitary erythema migrans in Georgia and South Carolina.

OBJECTIVE: To evaluate the incidence of Borrelia burgdorferi infection in humans with erythema migrans (EM) in 2 southeastern states. DESIGN: Prospective case series. SETTING: Family medicine practice at academic center. PATIENTS: Twenty-three patients with solitary EM lesions meeting Centers for Disease Control and Prevention (CDC) criteria for Lyme disease. INTERVENTIONS: Patients underwent clinical and serologic evaluation for evidence of B burgdorferi infection. All lesions underwent photography, biopsy, culture and histopathologic and polymerase chain reaction analysis for B burgdorferi infection. Patients were treated with doxycycline hyclate and followed up clinically and serologically. MAIN OUTCOME MEASURES: Disappearance of EM lesions and associated clinical symptoms in response to antibiotic therapy; short-term and follow-up serologic assays for diagnostic antibody; growth of spirochetes from tissue biopsy specimens in Barbour-Stoenner-Kelly II media; special histopathologic stains of tissue for spirochetes; and polymerase chain reaction assays of tissue biopsy specimens for established DNA sequences of B burgdorferi. RESULTS: The EM lesions ranged from 5 to 20 cm (average, 9.6 cm). Five patients (22%) had mild systemic symptoms. All lesions and associated symptoms resolved with antibiotic therapy. Overall, 7 patients (30%) had some evidence of B burgdorferi infection. Cultures from 1 patient (4%) yielded spirochetes, characterized as Borrelia garinii, a European strain not known to occur in the United States; 3 patients (13%) demonstrated spirochetallike forms on special histologic stains; 5 patients (22%) had positive polymerase chain reaction findings with primers for flagellin DNA sequences; and 2 patients (9%) were seropositive for B burgdorferi infection using recommended 2-step CDC methods. No late clinical sequelae were observed after treatment. CONCLUSIONS: The EM lesions we observed are consistent with early Lyme disease occurring elsewhere, but laboratory confirmation of B burgdorferi infection is lacking in at least 16 cases (70%) analyzed using available methods. Genetically variable strains of B burgdorferi, alternative Borrelia species, or novel, uncharacterized infectious agents may account for most of the observed EM lesions.

Sickle cell telemedicine and standard clinical encounters: a comparison of patient satisfaction.

OBJECTIVES: To determine patient satisfaction with telemedicine encounters among adults with sickle cell disease and compare their scores with SCD patients who have standard medical encounters (as controls). METHODS: Adults patients were recruited from a list of participants in sickle cell telemedicine clinics and prospectively at the time of clinic encounter. Patients were assigned to telemedicine or standard encounter groups. Demographic and pertinent clinical data were obtained for all subjects, and the Client Satisfaction Questionnaire (CSQ-8) was administered. Patients were also asked for open-ended comments regarding their satisfaction with the service. Their responses were recorded verbatim. RESULTS: Patients with telemedicine (n = 60) and standard encounters (n = 60) were comparable in gender, genotype, education, employment, and mean number of sickle cell disease-related complications. Patients in the telemedicine group were younger (p< 0.005), more likely to have Medicaid insurance (p = 0.009), and more likely be taking hydroxyurea (p = 0.003) than patients in the control encounter group. Mean CSQ scores for the telemedicine group were high (total: 28.82+/-3.06), and there was no difference for any item between encounter groups (p = 0.389). Patients in the standard encounter group were more likely to provide positive open-ended comments regarding the encounter (95% vs. 70%; p = 0.001). Negative comments were generally in the area of confidentiality. CONCLUSIONS: While some patients expressed concern about confidentiality with telemedicine, the benefits of improved access and continuity of care were recognized, and overall satisfaction with telemedicine was high. These findings support the use of telemedicine as an acceptable health care delivery option for rural, underserved populations with sickle cell disease.

Lyme disease update. Current approach to early, disseminated, and late disease.

A rational approach to diagnosis and treatment of Lyme disease requires an understanding of the endemic range of the tick vectors for B burgdorferi, the epidemiologic risk factors, and the spectrum of clinical manifestations. A two-step approach to serologic testing (ELISA followed by Western blot analysis of positive or equivocal results) can be useful if the pretest likelihood of Lyme disease is higher than 20%. Consideration should be given to the possibility of (1) a noninfectious disease with clinical features similar to those of Lyme disease or (2) coinfection with a second tick-transmitted organism. Late Lyme disease must be distinguished by clinical characteristics from fibromyalgia (the commonest source of misdiagnosis in several studies). Antibiotic therapy should be tailored to the extent of disease and limited to 4 weeks in most cases. Human vaccines based on an outer-surface protein from B burgdorferi have been tested in large-scale US clinical trials and may soon be approved for use in persons whose occupational or recreational activities place them at risk for B burgdorferi exposure.

Using relative value units to measure faculty clinical productivity.

The objective of this project was to compare faculty productivity in teaching and nonteaching clinical settings. We hypothesized that teaching activity would have no impact on productivity. A mixed model, repeated measures analysis of variance was used to analyze average relative value units (RVUs) billed and to test for differences between clinics. Data were drawn from 4,956 clinical encounters made within a student, resident, and faculty clinic. Average RVUs per visit were similar in the three settings. Resident supervision increased faculty productivity, while student supervision had no impact on billed RVUs. Thus, RVUs can be used as a measure of faculty clinical productivity in different settings in an academic medical center. Precepting students does not appear to affect clinical productivity.

Azithromycin compared with amoxicillin in the treatment of erythema migrans. A double-blind, randomized, controlled trial.

OBJECTIVE: To determine whether azithromycin or amoxicillin is more efficacious for the treatment of erythema migrans skin lesions, which are characteristic of Lyme disease. DESIGN: Randomized, double-blind, double-dummy, multicenter study. Acute manifestations and sequelae were assessed using a standardized format. Baseline clinical characteristics and response were correlated with serologic results. Patients were followed for 180 days. SETTING: 12 outpatient centers in eight states. PATIENTS: 246 adult patients with erythema migrans lesions at least 5 cm in diameter were enrolled and were stratified by the presence of flu-like symptoms (such as fever, chills, headache, malaise, fatigue, arthralgias, and myalgias) before randomization. INTERVENTION: Oral treatment with either amoxicillin, 500 mg three times daily for 20 days, or azithromycin, 500 mg once daily for 7 days. Patients who received azithromycin also received a dummy placebo so that the dosing schedules were identical. RESULTS: Of 217 evaluable patients, those treated with amoxicillin were significantly more likely than those treated with azithromycin to achieve complete resolution of disease at day 20, the end of therapy (88% compared with 76%; P=0.024). More azithromycin recipients (16%) than amoxicillin recipients (4%) had relapse (P=0.005). A partial response at day 20 was highly predictive of relapse (27% of partial responders had relapse compared with 6% of complete responders; P<0.001). For patients treated with azithromycin, development of an antibody response increased the possibility of achieving a complete response (81% of seropositive patients achieved a complete response compared with 60% of seronegative patients; P=0.043). Patients with multiple erythema migrans lesions were more likely than patients with single erythema migrans lesions (P<0.001) to have a positive antibody titer at baseline (63% compared with 17% for IgM; 39% compared with 16% for IgG). Fifty-seven percent of patients who had relapse were seronegative at the time of relapse. CONCLUSIONS: A 20-day course of amoxicillin was found to be an effective regimen for erythema migrans. Most patients were seronegative for Borrelia burgdorferi at the time of presentation with erythema migrans (65%) and at the time of relapse (57%).

Empiric parenteral antibiotic treatment of patients with fibromyalgia and fatigue and a positive serologic result for Lyme disease. A cost-effectiveness analysis.

PURPOSE: To examine the cost-effectiveness of empirical, parenteral antibiotic treatment of patients with chronic fatigue and myalgia and a positive serologic result for Lyme disease who lack classic manifestations. DATA SOURCES: Peer-reviewed journals, opinion of experts in the field, and published epidemiologic reports. STUDY SELECTION: Consensus by authors on articles that indicated methods for patient selection; on criteria used for diagnosis; on immunologic methods used for classifying patients; on the dose and duration of therapy; and on criteria by which responses to therapy were ascertained. DATA EXTRACTION: In a cost-effectiveness model, the costs and benefits of empirical parenteral therapy for patients seropositive for Lyme disease were compared with a strategy in which only patients having classical symptoms of Lyme disease were treated. DATA SYNTHESIS: In areas endemic for Lyme disease, the incidence of false-positive serologic results in patients with nonspecific myalgia or fatigue exceeds by four to one the incidence of true-positive results in patients with nonclassical infections. Treatment of the former group of patients costs $86,221 for each true-positive patient treated. The empirical strategy causes 29 cases of drug toxicity for every case in the more conservative strategy. If patients were willing to pay $3485 to eliminate anxiety about not treating possible true Lyme disease, the empirical strategy would break even. CONCLUSION: For most patients with a positive Lyme antibody titer whose only symptoms are nonspecific myalgia or fatigue the risks and costs of empirical parenteral antibiotic therapy exceed the benefits. Only when the value of patient anxiety about leaving a positive test untreated exceeds the cost of such therapy is the empirical treatment cost-effective.

Integrating general medicine and rheumatology training in the outpatient setting: a practice model.

The authors describe a primary care-based educational and practice model that integrates general medicine resident education in outpatient rheumatology with specialty fellowship training. Compared with the use of traditional specialty clinics, the model provides better access and service to patients and more appropriate training for residents. Revenues from clinical service delivered by faculty-supervised residents and fellows support 80% of the operating costs and educational activities of the model. The conceptual framework for the model reconciles the educational goals and practice philosophies of general medicine and specialty training and is applicable to training in other predominantly outpatient specialty areas.

Serologic diagnosis of Lyme disease using recombinant outer surface proteins A and B and flagellin.

Recombinant (r) outer surface proteins (Osp) A and B, flagellin, and an immunogenic region of flagellin (41-G) from Borrelia burgdorferi were evaluated using immunoblot and ELISA for usefulness as substrates in diagnostic testing for Lyme disease. Antibodies to rOspA, rOspB, and r-flagellin were detected by immunoblot and ELISA using the recombinant proteins. Patients with late disease responded to rOspA, rOspB, and r-flagellin, or only to r-flagellin, whereas patients with early disease showed no response or responded only to r-flagellin. Patients who developed antibodies to r-flagellin also responded to 41-G. The data suggest that recombinant B. burgdorferi antigens can serve as substrates for immunoblot and ELISA, which may be helpful in diagnosing Lyme disease.

Lyme disease and radiologic findings in Lyme arthritis.

Lyme disease typically begins in the spring or summer months, with a pathognomonic skin lesion and associated flulike or meningitislike symptoms. If the patient is not treated during this early stage, cardiac, neurologic, or musculoskeletal manifestations may occur weeks to months later. Although the clinical picture of Lyme disease is extremely variable, the diagnosis can be made in most cases by recognizing the typical patterns of organ involvement and associated immunologic abnormalities.

Antibiotic treatment of Lyme disease. Current recommendations by stage and extent of infection.

Much has been learned about Lyme disease over the past several years, but much remains to be learned. Careful clinical observation has led to elucidation of the natural history of this disease, and further clinical observations are needed to unravel the remaining areas of uncertainty. It is by no means clear that all the symptoms attributed to Lyme disease today actually represent true manifestations of Borrelia burgdorferi infection or that patients with well-documented Lyme disease whose symptoms do not respond to antibiotic therapy have persistent infection. Immunologically mediated mechanisms may be responsible for the chronic disease manifestations that seem so resistant to antibiotics. Uncovering answers to these questions requires the close collaboration of astute practicing physicians and biomedical scientists working together for their patients' benefit.

Treatment of early Lyme disease.

PURPOSE: To compare the safety and efficacy of azithromycin, amoxicillin/probenecid, and doxycycline for the treatment of early Lyme disease, to identify risk factors for treatment failure, and to describe the serologic response in treated patients. PATIENTS AND METHODS: Fifty-five patients with erythema migrans and two patients with flu-like symptoms alone and fourfold changes in antibody titers to Borrelia burgdorferi were randomized to receive (1) oral azithromycin, 500 mg on the first day followed by 250 mg once a day for 4 days; (2) oral amoxicillin 500 mg and probenecid 500 mg, three times a day for each for 10 days; or (3) doxcycline, 100 mg twice a day for 10 days. If symptoms were still present at 10 days, treatment was extended with amoxicillin/probenecid or doxycycline for 10 more days. Evaluations were done at study entry and 10, 30, and 180 days later. RESULTS: Three of the patients who initially had symptoms suggestive of spread of the spirochete to the nervous system, one from each antibiotic treatment group, subsequently developed neurologic abnormalities, but symptoms in the other 54 patients resolved within 3 to 30 days after study entry. Six of the 19 patients (32%) (95% confidence interval, 13% to 57%) given amoxicillin/probenecid developed a drug eruption, whereas none of the patients given azithromycin or doxycycline had this complication. The presence of dysesthesias at study entry was the only risk factor significantly associated with treatment failure (p less than 0.001). By convalescence, 72% of the patients were seropositive, and 56% still had detectable IgM responses to the spirochete 6 months later. CONCLUSIONS: The three antibiotic regimens tested in this study were generally effective for the treatment of early Lyme disease, but the regimens differ in the frequency of side effects and in ease of administration.