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Lyme disease is transmitted by the bite of certain Ixodes ticks, which can also transmit Anaplasma phagocytophilum , the cause of human granulocytic anaplasmosis (HGA). Although culture can be used to identify patients infected with A. phagocytophilum and is the microbiologic gold standard, few studies have evaluated culture-confirmed patients with HGA. We conducted a prospective study in which blood culture was used to detect HGA infection in patients with a compatible clinical illness. Early Lyme disease was defined by the presence of erythema migrans. The epidemiologic, clinical, and laboratory features of 44 patients with culture-confirmed HGA were compared with those of a convenience sample of 62 patients with early Lyme disease. Coinfected patients were excluded. Patients with HGA had more symptoms ( P = 0.003) and had a higher body temperature on presentation ( P < 0.001) than patients with early Lyme disease. HGA patients were also more likely to have a headache, dizziness, myalgias, abdominal pain, anorexia, leukopenia, lymphopenia, thrombocytopenia, or elevated liver enzymes. A direct correlation between the number of symptoms and the duration of illness at time of presentation (rho = 0.389, P = 0.009) was observed for HGA patients but not for patients with Lyme disease. In conclusion, although there are overlapping features, culture-confirmed HGA is a more severe illness than early Lyme disease.

Background. Lyme disease is transmitted by the bite of the Ixodes scapularis tick, which can also transmit Anaplasma phagocytophilum, the cause of human granulocytic anaplasmosis (HGA). Conflicting data exist on the frequency of coinfection and on whether Lyme-HGA coinfected patients have more symptoms than patients with Lyme disease alone. Methods. Blood culture and serology were used to detect HGA infection in patients with early Lyme disease who presented with erythema migrans. The rate of coinfection was determined using different definitions. The clinical and laboratory features of Lyme-HGA coinfection were compared with that of the individual infections. Results. Among 311 patients with erythema migrans, the frequency of coinfection with HGA varied from 2.3% to 10.0%, depending on the definition used (P< .001). Only 1 of 4 groups with presumed coinfection had significantly more symptoms than patients with Lyme disease alone P< .05. High fever and cytopenia were less common in Lyme-HGA coinfection than in patients with HGA alone. Conclusion. The results of this study indicate that how HGA is defined in patients with early Lyme disease has an impact on the apparent rate of coinfection and the severity of illness. The findings also suggest that HGA may be less severe than is usually believed, suggesting the existence of referral bias in testing patients preferentially who present with high fever or cytopenia.

Bloodstream invasion is an important event in the pathogenesis of the more serious manifestations of Lyme disease. The number of spirochetes in the blood of infected patients, however, has not been determined, and, therefore, it is unknown whether the number of spirochetes can be correlated with particular clinical or laboratory features. This study was designed to measure the level of Borrelia burgdorferi in the plasma of Lyme disease patients and correlate these levels with selected clinical and laboratory findings. Nested and quantitative polymerase chain reaction (qPCR) was employed to detect cell-associated flaB gene DNA in the plasma of untreated early Lyme disease patients with erythema migrans (EM). Twenty-nine (45.3%) of 64 patients had evidence of B. burgdorferi in their plasma by at least one of the PCR methods. For the 22 qPCR-positive patients, the mean number of flaB gene copies per mL of plasma was 4,660, with a range of 414 to 56,000. The number of flaB gene copies did not significantly correlate with any of the clinical, demographic, or laboratory variables assessed. For reasons discussed, we suggest caution in extrapolating an estimate of the number of viable Borrelia in plasma from the observed number of flaB copies.

Lyme disease is the most common tickborne disease in the United States [1]. Although the majority of cases are reported from the mid-Atlantic, northeastern, midwestern, and far western regions of the country, several hundreds of cases annually are reported from the southeast and south-central United States [1, 2]. Many of these cases are associated with an erythema migrans (EM)–like rash [3–6]. This skin lesion has followed the bite of Amblyomma americanum, a tick species found throughout the southeast and south-central United States [4, 7–9], and is alternatively referred to as southern tick–associated rash illness or Masters disease. A. americanum ticks are not infected with Borrelia burgdorferi but may be infected with a borrelial species different from both B. burgdorferi and the other Borrelia genospecies recognized to cause Lyme disease in Eurasia [10–19]. Barbour et al. [11] proposed the name Borrelia lonestari species novum. Until recently, it remained unclear whether A. americanum could transmit B. lonestari to humans or whether B. lonestari was the cause of (or even associated with) any clinical illness. In 2001, James et al. [18] documented the first such case. This patient developed an EM-like rash following the bite of an A. americanum tick during a trip to Maryland and North Carolina. James et al. [18] demonstrated by PCR amplification techniques that both the tick and the patient were infected with B. lonestari or a closely related bacterium. An important question is whether B. lonestari is the cause of the many cases reported as Lyme disease in southern and other regions of the United States where A. americanum ticks bite humans. In this article, we report results of a microbiologic evaluation of patients from Missouri with EM-like skin lesions and compare these results with those for patients from New York State with EM who were similarly evaluated during the same period.

Purpose To determine the long-term outcome of patients with culture-confirmed Lyme disease. Methods We analyzed data collected prospectively on adult patients from a highly endemic area in New York State who were diagnosed with early Lyme disease between 1991 and 1994. Patients with culture-confirmed erythema migrans were evaluated at baseline, 7 to 10 days, 21 to 28 days, 3 months, 6 months, 1 year, and annually thereafter. All patients were treated with antibiotics at the time of diagnosis. Results We evaluated 96 cases on 709 separate occasions (median, eight evaluations per case). The erythema migrans rash resolved within 3 weeks in all of the 94 evaluable cases, none of whom developed an objective extracutaneous manifestation of Lyme disease. Of the 81 cases who were followed for ≥1 year, all but 8 (10%) were asymptomatic at their last visit, a mean (± SD) of 5.6 ± 2.6 years into follow-up, and only 3 (4%) were symptomatic at every follow-up visit. Intercurrent tick bites were reported by 45 cases (47%), and 14 (15%) developed a second episode of erythema migrans. Four other cases who were asymptomatic seroconverted between years 2 and 5. Conclusion The long-term outcome of patients with erythema migrans after antibiotic therapy was excellent, but patients from a highly endemic area in New York State remained at high risk of re-exposure to ticks and reinfection. Subjective symptoms during follow-up evaluations tended to be mild to moderate, intermittent, and associated with more symptomatic illness at the time of initial diagnosis.

Lyme disease, the most commonly reported tick-borne infection in North America, is caused by infection with the spirochete Borrelia burgdorferi. Although an accurate clinical diagnosis can often be made based on the presence of erythema migrans, in research studies microbiologic or molecular microbiologic confirmation of the diagnosis may be required. In this study, we evaluated the sensitivity of 5 direct diagnostic methods (culture and nested polymerase chain reaction [PCR] of a 2-mm skin biopsy specimen, nested PCR and quantitative PCR (qPCR) performed on the same 1-mL aliquot of plasma and a novel qPCR-blood culture method) in 66 untreated adult patients with erythema migrans. Results of one or more of these tests were positive in 93.9% of the patients. Culture was more sensitive than PCR for both skin and blood, but the difference was only statistically significant for blood samples (P

Spirochetemia in US patients with extracutaneous manifestations of Lyme disease is not well documented. In this study, blood culture results were positive for 5 (19.2%; 95% confidence interval, 6.6%-39.4%) of 26 untreated adult patients with extracutaneous manifestations but only for patients with clinical evidence for a short duration of infection.

To investigate whether genetic diversity of Borrelia burgdorferi sensu stricto may affect the occurrence of hematogenous dissemination, 104 untreated adults with erythema migrans from a Lyme disease diagnostic center in Westchester County, New York, were studied. Cultured skin isolates were classified into 3 groups by a polymerase chain reaction amplification and restriction fragment length polymorphism (RFLP) method. A highly significant association between infecting RFLP type in skin and the presence of spirochetemia was found (P

We describe the clinical and laboratory manifestations of human granulocytic ehrlichiosis (HGE) in eight patients for whom cultures were positive for the HGE agent and compare them with 15 patients for whom cultures were negative but who fulfilled a modified New York State Surveillance definition for HGE. Polymerase chain reaction analysis was positive in 8 (100%) of 8 culture-positive cases vs. 3 (20%) of 15 culture-negative cases (P < .001), morulae were detected in 7 (100%) of 7 culture-positive cases in which tests were performed vs. 0 of 15 culture-negative cases (P < .001), and a fourfold change in antibody titer was demonstrated in 6 (75%) of 8 culture-positive cases vs. 9 (69%) of 13 culture-negative cases (P = not significant). Patients for whom cultures were positive had higher mean oral temperatures +/- SD at presentation than did patients for whom cultures were negative (38.6 degrees C +/- 0.7 degree C vs. 37.2 degrees C +/- 0.8 degree C, respectively; P = .002). Other symptoms and signs were not significantly different between the two groups. Multivariate analysis revealed that the lymphocyte count at presentation was significantly lower in culture-positive cases than in culture-negative cases. Clinical response to treatment was similar in the two groups. Culture confirmation of HGE is the gold standard for defining the sensitivity and specificity of other diagnostic tests presently being developed.

Background Erythema migrans is the most common manifestation of Lyme disease. Recurrences are not uncommon, and although they are usually attributed to reinfection rather than relapse of the original infection, this remains somewhat controversial. We used molecular typing of Borrelia burgdorferi isolates obtained from patients with culture-confirmed episodes of erythema migrans to distinguish between relapse and reinfection. Methods We determined the genotype of the gene encoding outer-surface protein C (ospC) of B. burgdorferi strains detected in cultures of skin or blood specimens obtained from patients with consecutive episodes of erythema migrans. After polymerase-chainreaction amplification, ospC genotyping was performed by means of reverse lineblot analysis or DNA sequencing of the nearly full-length gene. Most strains were further analyzed by determining the genotype according to the 16S–23S ribosomal RNA intergenic spacer type, multilocus sequence typing, or both. Patients received standard courses of antibiotics for erythema migrans. Results B. burgdorferi isolates obtained from 17 patients who received a diagnosis of erythema migrans between 1991 and 2011 and who had 22 paired episodes of this lesion (initial and second episodes) were available for testing. The ospC genotype was found to be different at each initial and second episode. Apparently identical genotypes were identified on more than one occasion in only one patient, at the first and third episodes, 5 years apart, but different genotypes were identified at the second and fourth episodes. Conclusions None of the 22 paired consecutive episodes of erythema migrans were associated with the same strain of B. burgdorferi on culture. Our data show that repeat episodes of erythema migrans in appropriately treated patients were due to reinfection and not relapse. (Funded by the National Institutes of Health and the William and Sylvia Silberstein Foundation.)

Bloodstream invasion in Lyme disease has been difficult to study because until recently blood culture methods were too insensitive to detect spirochetemia.To evaluate the clinical and laboratory features of spirochetemic patients.Cross-sectional study.Lyme Disease Diagnostic Center in Valhalla, New York, 1997 to 2002.213 untreated adults with erythema migrans.Blood culture for Borrelia burgdorferi.Symptom scores and selected laboratory measures.Spirochetemia was found in 93 (43.7%) patients. Spirochetemic patients were more often symptomatic (89.2% vs. 74.2%; P = 0.006) and more often had multiple erythema migrans lesions (41.9% vs. 15.0%; P0.001) than patients without spirochetemia. However, 8 (22.9%) of the 35 asymptomatic patients with a single skin lesion nevertheless had a positive blood culture. Risk for spirochetemia was present the day the patient noticed the lesion and continued for more than 2 weeks.Long-term outcome data were not available.The high rate, early onset, and prolonged duration of risk for spirochetemia explain why untreated patients with erythema migrans are at risk for dissemination of B. burgdorferi to anatomic sites beyond the lesion site. Differences in the strain of the infecting spirochete, as well as host factors, may be important determinants of hematogenous dissemination.

Background. The most common and most recognizable feature of Borrelia burgdorferi infection (Lyme disease) is the skin lesion erythema migrans (EM). An illness associated with an EM-like skin lesion, but which is not caused by B. burgdorferi, occurs in many southern states in the United States (southern tick—associated rash illness [STARI], also known as Masters disease).Methods. Clinical features of 21 cases of EM-like skin lesions in 21 patients from Missouri were compared in a prospective study with those of 101 cases in 97 patients with EM-like skin lesions from New York.Results. Among Missouri cases, the peak incidence of EM-like skin lesions occurred earlier in the year than it did among New York cases (P < .001). Case patients from Missouri were more likely to recall a tick bite than were case patients from New York (85.7% and 19.8%, respectively; P < .001), and the time period from tick bite to onset of the skin lesion was shorter among Missouri case patients (6.1 ± 4.2 days and 10.4 ± 6.1 days, respectively; P = .011). Missouri case patients were less likely to be symptomatic than were New York case patients (19.0% and 76.2%, respectively; P < .001), and Missouri case patients were less likely to have multiple skin lesions (4.8% and 26.7%, respectively; P = .042). EM-like lesions in Missouri cases were smaller in size than those in New York cases (8.3 ± 2.2 cm and 16.4 ± 11.5 cm, respectively; P < .001), more circular in shape (P = .004), and more likely to have central clearing (76.2% and 21.6%, respectively; P < .001). After antibiotic treatment, Missouri case patients recovered more rapidly than did New York case patients (P = .037).Conclusion. Cases of EM-like skin lesion in patients from Missouri and New York have distinct clinical presentations.

Background: Treatment of patients with early Lyme disease has trended toward longer duration despite the absence of supporting clinical trials. Objective: To evaluate different durations of oral doxycycline treatment and the combination of oral doxycycline and a single intravenous dose of ceftriaxone for treatment of patients with early Lyme disease. Design: Randomized, double-blind, placebo-controlled trial. Setting: Single-center university hospital. Patients: 180 patients with erythema migrans. Intervention: Ten days of oral doxycycline, with or without a single intravenous dose of ceftriaxone, or 20 days of oral doxycycline. Measurements: Outcome was based on clinical observations and neurocognitive testing. Efficacy was assessed at 20 days, 3 months, 12 months, and 30 months. Results: At all time points, the complete response rate was similar for the three treatment groups in both on-study and intention-to-treat analyses. In the on-study analysis, the complete response rate at 30 months was 83.9% in the 20-day doxycycline group, 90.3% in the 10-day doxycycline group, and 86.5% in the doxycycline-ceftriaxone group (P> 0.2). The only patient with treatment failure (10-day doxycycline group) developed meningitis on day 18. There were no significant differences in the results of neurocognitive testing among the three treatment groups and a separate control group without Lyme disease. Diarrhea occurred significantly more often in the doxycycline-ceftriaxone group (35%) than in either of the other two groups (P < 0.001). Conclusions: Extending treatment with doxycycline from 10 to 20 days or adding one dose of ceftriaxone to the beginning of a 10-day course of doxycycline did not enhance therapeutic efficacy in patients with erythema migrans. Regardless of regimen, objective evidence of treatment failure was extremely rare.

A multicenter, double-blinded, placebo-controlled study was done comparing a 30-microgram dose of a single protein recombinant OspA vaccine preparation with a saline placebo for efficacy in prevention of Lyme disease in humans. The OspA vaccine (30-microgram dose) or saline placebo was given intramuscularly at day 0, 1 month later, and 12 months later. Cases of possible Lyme disease were evaluated clinically and using culture, polymerase chain reaction and immunoblot assays. Safety data are being analyzed separately. 1,634 adult volunteers were enrolled at a single center in New York State. Vaccine efficacy during the first year was 40% and during the second 37%. Compared with placebo, the OspA vaccine significantly reduced the frequency of Lyme disease during the 2-year study period (P0.04, one-tailed Fisher's exact test). Vaccine efficacy was restricted to volunteers under 60 years old (50% vs 9%, P0.03, two-tailed Fisher's exact test). A recombinant OspA vaccine preparation was found to have moderate activity in preventing Lyme disease in adults under 60 years old from New York State. Reasons for vaccine failure need to be addressed and a risk benefit ratio calculated.

The standard of therapy for the high risk adult neutropenic host being treated with broad spectrum antibiotics for fever has been to continue intravenous antibiotics until neutropenia resolves. We performed a small, limited pilot study to determine if it is safe to switch these patients to oral monotherapy with ciprofloxacin. Ten patients with hematologic malignancies who hador = 108 granulocytes/mm3 after cytoreductive therapy and were afebrile for at least five days had intravenous antibiotics discontinued and were placed on oral ciprofloxacin. Eight patients were able to be discharged from the hospital and seven were treated without the need for reinstitution of intravenous therapy. Of the three failures, one developed fever with a new bloodstream infection and two developed fever with relapse of leukemia. Patients remained on ciprofloxacin an average of 14.5 days (range 4 to 35 days). Aggregate cost savings for the 10 patients from this approach were estimated to be $11,400 for antibiotics and $88,800 for hospitalization. If corroborated in larger, randomized studies, the use of "stepdown monotherapy" may be a cost effective approach to the management of the stable neutropenic patient.

• Background.— Lyme disease is the most common vector-borne disease in the United States. The characteristic rash, erythema migrans, is an early sign of the disease. Clinical criteria remain the "gold standard" for diagnosis at this stage of illness. Observations.— Five (8%) of 65 patients with erythema migrans seen in a Lyme disease diagnostic center in Westchester County, New York, had a lesion with vesicles. Borrelia burgdorferi was cultured from two of five. In one case the positive culture came from a swab of the blister fluid. Conclusions.— Recognition of erythema migrans and its variants is important, since early treatment of Lyme disease may prevent late complications. Vesicular erythema migrans should be added to the differential diagnosis of inflammatory vesicular rashes in the appropriate clinical setting. (Arch Dermatol.1992;128:1495-1498)