The impact of strain-specific immunity on Lyme disease incidence is spatially heterogeneous.

Lyme disease, caused by the bacterium Borrelia burgdorferi, is the most common tick-borne infection in the US. Recent studies have demonstrated that the incidence of human Lyme disease would have been even greater were it not for the presence of strain-specific immunity, which protects previously infected patients against subsequent infections by the same B. burgdorferi strain. Here, spatial heterogeneity is incorporated into epidemiological models to accurately estimate the impact of strain-specific immunity on human Lyme disease incidence. The estimated reduction in the number of Lyme disease cases is greater in epidemiologic models that explicitly include the spatial distribution of Lyme disease cases reported at the county level than those that utilize nationwide data. strain-specific immunity has the greatest epidemiologic impact in geographic areas with the highest Lyme disease incidence due to the greater proportion of people that have been previously infected and have developed strain-specific immunity.

Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis - United States.

Tickborne rickettsial diseases continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of low-cost, effective antibacterial therapy. Recognition early in the clinical course is critical because this is the period when antibacterial therapy is most effective. Early signs and symptoms of these illnesses are nonspecific or mimic other illnesses, which can make diagnosis challenging. Previously undescribed tickborne rickettsial diseases continue to be recognized, and since 2004, three additional agents have been described as causes of human disease in the United States: Rickettsia parkeri, Ehrlichia muris-like agent, and Rickettsia species 364D. This report updates the 2006 CDC recommendations on the diagnosis and management of tickborne rickettsial diseases in the United States and includes information on the practical aspects of epidemiology, clinical assessment, treatment, laboratory diagnosis, and prevention of tickborne rickettsial diseases. The CDC Rickettsial Zoonoses Branch, in consultation with external clinical and academic specialists and public health professionals, developed this report to assist health care providers and public health professionals to 1) recognize key epidemiologic features and clinical manifestations of tickborne rickettsial diseases, 2) recognize that doxycycline is the treatment of choice for suspected tickborne rickettsial diseases in adults and children, 3) understand that early empiric antibacterial therapy can prevent severe disease and death, 4) request the appropriate confirmatory diagnostic tests and understand their usefulness and limitations, and 5) report probable and confirmed cases of tickborne rickettsial diseases to public health authorities.

Identification of Dietzia spp. from Cardiac Tissue by 16S rRNA PCR in a Patient with Culture-Negative Device-Associated Endocarditis: A Case Report and Review of the Literature.

The genus Dietzia was recently distinguished from other actinomycetes such as Rhodococcus. While these organisms are known to be distributed widely in the environment, over the past decade several novel species have been described and isolated from human clinical specimens. Here we describe the identification of Dietzia natronolimnaea/D. cercidiphylli by PCR amplification and sequencing of the 16S rRNA encoding gene from cardiac tissue in a patient with culture-negative device-associated endocarditis.

Public health impact of strain specific immunity to Borrelia burgdorferi.

BACKGROUND: Lyme disease, caused by Borrelia burgdorferi, is the most common tick-borne infection in the United States. Although humans can be infected by at least 16 different strains of B. burgdorferi, the overwhelming majority of infections are due to only four strains. It was recently demonstrated that patients who are treated for early Lyme disease develop immunity to the specific strain of B. burgdorferi that caused their infection. The aim of this study is to estimate the reduction in cases of Lyme disease in the United States that may occur as a result of type specific immunity. METHODS: The analysis was performed based on three analytical models that assessed the effects of type specific immunity. Observational data on the frequency with which different B. burgdorferi strains cause human infection in culture-confirmed patients with an initial episode of erythema migrans diagnosed between 1991 and 2005 in the Northeastern United States were used in the analyses. RESULTS: Assuming a reinfection rate of 3 % and a total incidence of Lyme disease per year of 300,000, the estimated number of averted cases of Lyme disease per year ranges from 319 to 2378 depending on the duration of type specific immunity and the model used. CONCLUSION: Given the assumptions of the analyses, this analysis suggests that type specific immunity is likely to have public health significance in the United States.

Long-term Assessment of Post-Treatment Symptoms in Patients With Culture-Confirmed Early Lyme Disease.

BACKGROUND: Lyme disease patients with erythema migrans are said to have post-treatment Lyme disease symptoms (PTLDS) if there is persistence of subjective symptoms for at least 6 months following antibiotic treatment and resolution of the skin lesion. The purpose of this study was to characterize PTLDS in patients with culture-confirmed early Lyme disease followed for >10 years. METHODS: Adult patients with erythema migrans with a positive skin or blood culture for Borrelia burgdorferi were enrolled in a prospective study beginning in 1991 and followed up at 6 months and annually thereafter to determine the long-term outcome of this infection. The genotype of the infecting strain of B. burgdorferi was evaluated in subjects with PTLDS. RESULTS: One hundred twenty-eight subjects with culture-confirmed early Lyme disease, of whom 55% were male, were followed for a mean ± SD of 14.98 ± 2.71 years (median = 15 years; range = 11-20 years). Fourteen (10.9%) were regarded as having possible PTLDS, but only 6 (4.7%) had PTLDS documented at their last study visit. Nine (64.3%) had only a single symptom. None of the 6 with PTLDS at their last visit was considered to be functionally impaired by the symptom(s). PTLDS was not associated with a particular genotype of B. burgdorferi. CONCLUSIONS: PTLDS may persist for >10 years in some patients with culture-confirmed early Lyme disease. Such long-standing symptoms were not associated with functional impairment or a particular strain of B. burgdorferi.

Erythema migrans.

Erythema migrans (EM) is the most common objective manifestation of Borrelia burgdorferi infection. Systemic symptoms are usually present. Most patients do not recall a preceding tick bite. Despite a characteristic appearance, EM is not pathognomonic for Lyme disease and must be distinguished from other similar appearing skin lesions. EM is a clinical diagnosis; serologic and PCR assays are unnecessary. Leukopenia and thrombocytopenia are indicative of either an alternative diagnosis, or coinfection with another tick-borne pathogen. When EM is promptly treated with appropriate antimicrobial agents, the prognosis is excellent. Persons in endemic areas should take measures to prevent tick bites.

Long-term assessment of health-related quality of life in patients with culture-confirmed early Lyme disease.

The health-related quality of life of 100 subjects with culture-confirmed early Lyme disease enrolled in a prospective study with annual follow-up visits was evaluated using the 36-Item Short Form General Health Survey version 2 (SF-36v2) questionnaire at 11-20 years after diagnosis. The mean summary scores of physical and mental health were similar to those of the general population.

Long-Term Assessment of Fibromyalgia in Patients with Culture-Confirmed Lyme Disease.

Background: Fibromyalgia occurs in 2% to 8% of the general population. One of the triggers may be Lyme disease. Methods: Patients with culture-confirmed Lyme disease who originally presented with erythema migrans have been evaluated annually in a prospective study to determine their long-term outcome. In 2011-2013, subjects were evaluated for fibromyalgia by interview and tender point examination. Results: 100 subjects were assessed, 52% of whom were male; the mean age was 64.9 years (median 64 years, range 42-86 years). The mean duration of follow-up was 15.4 years (median 16 years, range 11-20 years). At least twenty-four (24%) subjects had experienced a second episode of erythema migrans before the evaluation for fibromyalgia. One patient (1%, 95% C.I.: 0.025 to 5.4%) met criteria for fibromyalgia. The symptoms consistent with fibromyalgia began more than 19 years after Lyme disease was diagnosed. Conclusions: Fibromyalgia was observed in only 1% of 100 patients with culture-confirmed early Lyme disease, a frequency consistent with that found for the general population. This article is protected by copyright. All rights reserved.

Long-term assessment of fatigue in patients with culture-confirmed Lyme disease.

BACKGROUND: Fatigue is a common symptom with numerous causes. Severe fatigue is thought to be an important manifestation of post-treatment Lyme disease syndrome. The frequency with which severe fatigue occurs as a long-term sequela in prospectively followed patients with Lyme disease is unknown. METHODS: Patients with culture-confirmed Lyme disease who originally presented with erythema migrans have been evaluated annually in a prospective study to determine their long-term outcome. In 2011-2013, subjects were evaluated for fatigue using an 11-item Fatigue Severity Scale (FSS-11) that has been used in studies of post-treatment Lyme disease syndrome. An FSS-11 score of ≥4.0 is indicative of severe fatigue. RESULTS: A total of 100 subjects were assessed, 52% of whom were male; the mean age was 64.9 years (range, 42-86 years). The mean duration of follow-up was 15.4 years (range, 11-20 years). Nine subjects had severe fatigue but in none as a consequence of Lyme disease. Only 3 subjects were thought to possibly have persistent fatigue from Lyme disease. The FSS-11 value for these 3 individuals was less than 4, averaging 2.27, and none had functional impairment. CONCLUSIONS: Severe fatigue was found in 9 patients (9%) with culture-confirmed early Lyme disease at 11 to 20 years after presentation, but was due to causes other than Lyme disease. Fatigue of lesser severity was possibly due to Lyme disease, but was found in only 3% of 100 patients, and therefore is rarely a long-term complication of this infection.

Evidence for strain-specific immunity in patients treated for early lyme disease.

Lyme disease, caused by Borrelia burgdorferi, is the most commonly reported vector-borne disease in the United States. Many patients treated for early Lyme disease incur another infection in subsequent years, suggesting that previous exposure to B. burgdorferi may not elicit a protective immune response. However, identical strains are almost never detected from patients who have been infected multiple times, suggesting that B. burgdorferi exposure may elicit strain-specific immunity. Probabilistic and simulation models assuming biologically realistic data derived from patients in the northeastern United States suggest that patients treated for early Lyme disease develop protective immunity that is strain specific and lasts for at least 6 years.

Differences and similarities between culture-confirmed human granulocytic anaplasmosis and early lyme disease.

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.

Single-tier testing with the C6 peptide ELISA kit compared with two-tier testing for Lyme disease.

For the diagnosis of Lyme disease, the 2-tier serologic testing protocol for Lyme disease has a number of shortcomings including low sensitivity in early disease; increased cost, time, and labor; and subjectivity in the interpretation of immunoblots. In this study, the diagnostic accuracy of a single-tier commercial C6 ELISA kit was compared with 2-tier testing. The results showed that the C6 ELISA was significantly more sensitive than 2-tier testing with sensitivities of 66.5% (95% confidence interval [CI] 61.7-71.1) and 35.2% (95% CI 30.6-40.1), respectively (P < 0.001) in 403 sera from patients with erythema migrans. The C6 ELISA had sensitivity statistically comparable to 2-tier testing in sera from Lyme disease patients with early neurologic manifestations (88.6% versus 77.3%, P = 0.13) or arthritis (98.3% versus 95.6%, P = 0.38). The specificities of C6 ELISA and 2-tier testing in over 2200 blood donors, patients with other conditions, and Lyme disease vaccine recipients were found to be 98.9% and 99.5%, respectively (P < 0.05, 95% CI surrounding the 0.6 percentage point difference of 0.04 to 1.15). In conclusion, using a reference standard of 2-tier testing, the C6 ELISA as a single-step serodiagnostic test provided increased sensitivity in early Lyme disease with comparable sensitivity in later manifestations of Lyme disease. The C6 ELISA had slightly decreased specificity. Future studies should evaluate the performance of the C6 ELISA compared with 2-tier testing in routine clinical practice.

Differentiation of reinfection from relapse in recurrent Lyme disease.

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-chain-reaction amplification, ospC genotyping was performed by means of reverse line-blot 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.).

The amber theory of Lyme arthritis: initial description and clinical implications.

Lyme arthritis differs in many respects from other bacterial causes of arthritis. Based on an observation made for a patient with Lyme arthritis, we propose that the pathogenesis of joint swelling in Lyme arthritis is due to the introduction into the joint space of non-viable spirochetes or more likely spirochetal debris enmeshed in a host-derived fibrinous or collagenous matrix. This "amber" hypothesis can account for the clinical and laboratory features of Lyme arthritis and is amenable to experimental validation. Validation would directly impact the clinical management of patients with Lyme arthritis.

Antiscience and ethical concerns associated with advocacy of Lyme disease.

Advocacy for Lyme disease has become an increasingly important part of an antiscience movement that denies both the viral cause of AIDS and the benefits of vaccines and that supports unproven (sometimes dangerous) alternative medical treatments. Some activists portray Lyme disease, a geographically limited tick-borne infection, as a disease that is insidious, ubiquitous, difficult to diagnose, and almost incurable; they also propose that the disease causes mainly non-specific symptoms that can be treated only with long-term antibiotics and other unorthodox and unvalidated treatments. Similar to other antiscience groups, these advocates have created a pseudoscientific and alternative selection of practitioners, research, and publications and have coordinated public protests, accused opponents of both corruption and conspiracy, and spurred legislative efforts to subvert evidence-based medicine and peer-reviewed science. The relations and actions of some activists, medical practitioners, and commercial bodies involved in Lyme disease advocacy pose a threat to public health.

Prospective evaluation of 2009 H1N1 influenza A in patients admitted with fever to an oncology unit.

We prospectively evaluated all oncology inpatients for 2009 H1N1 influenza virus. All patients recovered completely. Evaluating all oncology patients with fever for influenza involved overtreatment of influenza-negative patients and involved a significant infection control burden. However, early antiviral intervention could have contributed to a favorable outcome.

Comparison of erythema migrans caused by Borrelia burgdorferi and Borrelia garinii.

BACKGROUND: A comparison of patients with erythema migrans due to Borrelia garinii versus Borrelia burgdorferi has not been reported. PATIENTS AND METHODS: One hundred nineteen patients from New York State with erythema migrans caused by B. burgdorferi were compared with 116 patients from Slovenia with erythema migrans due to B. garinii infection. RESULTS: Patients with B. garinii infection were older, more often reported a tick bite, and developed larger lesions (median largest diameter: 18 and 14 cm, respectively; p = 0.01) that more often had central clearing (61.2% compared with 35.3%; p < 0.0001). Patients infected with B. burgdorferi, however, more often had systemic symptoms (68.9% vs. 37.1%; p < 0.0001), including fatigue (p < 0.0001), arthralgia (p = 0.0003), myalgia (p < 0.0001), headache (p = 0.0008), fever and/or chills (p < 0.0001), and stiff neck (p < 0.0001), and more often had abnormal physical findings (57.1% compared with 11.2%; p < 0.0001), such as fever (p = 0.0002) or regional lymphadenopathy (p < 0.0001). There was a trend for more patients with B. burgdorferi infection to have multiple erythema migrans skin lesions (13.4% compared with 5.2%; p = 0.051), and among patients with multiple erythema migrans the number of lesions was greater in B. burgdorferi-infected patients (median: 5.5 compared with 2.0; p = 0.006). CONCLUSIONS: The results of the present study indicate that in patients with erythema migrans the clinical features vary according to whether infection is caused by B. garinii or B. burgdorferi.

Babesiosis in Lower Hudson Valley, New York, USA.

Although Lyme disease has been endemic to parts of the Lower Hudson Valley of New York, United States, for >2 decades, babesiosis has emerged there only since 2001. The number of Lower Hudson Valley residents in whom babesiosis was diagnosed increased 20-fold, from 6 to 119 cases per year during 2001-2008, compared with an ≈1.6-fold increase for the rest of New York. During 2002-2009, a total of 19 patients with babesiosis were hospitalized on 22 occasions at the regional tertiary care center. Concurrent conditions included advanced age, malignancies, splenectomy, and AIDS. Two patients acquired the infection from blood transfusions and 1 from perinatal exposure, rather than from a tick bite. One patient died. Clinicians should consider babesiosis in persons with fever and hemolytic anemia who have had tick exposure or have received blood products.

Scientific evidence and best patient care practices should guide the ethics of Lyme disease activism.

Johnson and Stricker published an opinion piece in the Journal of Medical Ethics presenting their perspective on the 2008 agreement between the Infectious Diseases Society of America (IDSA) and the Connecticut Attorney General with regard to the 2006 IDSA treatment guideline for Lyme disease. Their writings indicate that these authors hold unconventional views of a relatively common tick-transmitted bacterial infection caused by the spirochete Borrelia burgdorferi. Therefore, it should come as no surprise that their opinions would clash with the IDSA's evidence-based guidelines for the diagnosis and treatment of Lyme disease. Their allegations of conflict of interest against the IDSA resemble those made against the National Institutes of Health, the Food and Drug Administration and the Centers for Disease Control and Prevention in 2000, which were found to be baseless. It is the responsibility of all physicians and medical scientists to stand up to antiscientific, baseless and unethical attacks on those who support an evidence-based approach to caring for patients.