Early Lyme disease with spirochetemia - diagnosed by DNA sequencing

<p>Abstract</p> <p>Background</p> <p>A sensitive and analytically specific nucleic acid amplification test (NAAT) is valuable in confirming the diagnosis of early Lyme disease at the stage of spirochetemia.</p> <p>Findings</p> <p>Venous blood drawn from patients with clinical presentations of Lyme disease was tested for the standard 2-tier screen and Western Blot serology assay for Lyme disease, and also by a nested polymerase chain reaction (PCR) for <it>B. burgdorferi </it>sensu lato 16S ribosomal DNA. The PCR amplicon was sequenced for <it>B. burgdorferi </it>genomic DNA validation. A total of 130 patients visiting emergency room (ER) or Walk-in clinic (WALKIN), and 333 patients referred through the private physicians' offices were studied. While 5.4% of the ER/WALKIN patients showed DNA evidence of spirochetemia, none (0%) of the patients referred from private physicians' offices were DNA-positive. In contrast, while 8.4% of the patients referred from private physicians' offices were positive for the 2-tier Lyme serology assay, only 1.5% of the ER/WALKIN patients were positive for this antibody test. The 2-tier serology assay missed 85.7% of the cases of early Lyme disease with spirochetemia. The latter diagnosis was confirmed by DNA sequencing.</p> <p>Conclusion</p> <p>Nested PCR followed by automated DNA sequencing is a valuable supplement to the standard 2-tier antibody assay in the diagnosis of early Lyme disease with spirochetemia. The best time to test for Lyme spirochetemia is when the patients living in the Lyme disease endemic areas develop unexplained symptoms or clinical manifestations that are consistent with Lyme disease early in the course of their illness.</p

Biodiversity of Borrelia burgdorferi Strains in Tissues of Lyme Disease Patients

Plant and animal biodiversity are essential to ecosystem health and can provide benefits to humans ranging from aesthetics to maintaining air quality. Although the importance of biodiversity to ecology and conservation biology is obvious, such measures have not been applied to strains of an invasive bacterium found in human tissues during infection. In this study, we compared the strain biodiversity of Borrelia burgdorferi found in tick populations with that found in skin, blood, synovial fluid or cerebrospinal fluid of Lyme disease patients. The biodiversity of B. burgdorferi strains is significantly greater in tick populations than in the skin of patients with erythema migrans. In turn, strains from skin are significantly more diverse than strains at any of the disseminated sites. The cerebrospinal fluid of patients with neurologic Lyme disease harbored the least pathogen biodiversity. These results suggest that human tissues act as niches that can allow entry to or maintain only a subset of the total pathogen population. These data help to explain prior clinical observations on the natural history of B. burgdorferi infection and raise several questions that may help to direct future research to better understand the pathogenesis of this infection

Diagnostic challenges of early Lyme disease: Lessons from a community case series

<p>Abstract</p> <p>Background</p> <p>Lyme disease, the most common vector-borne infection in North America, is increasingly reported. When the characteristic rash, erythema migrans, is not recognized and treated, delayed manifestations of disseminated infection may occur. The accuracy of diagnosis and treatment of early Lyme disease in the community is unknown.</p> <p>Methods</p> <p>A retrospective, consecutive case series of 165 patients presenting for possible early Lyme disease between August 1, 2002 and August 1, 2007 to a community-based Lyme referral practice in Maryland. All patients had acute symptoms of less than or equal to 12 weeks duration. Patients were categorized according to the Centers for Disease Control and Prevention criteria and data were collected on presenting history, physical findings, laboratory serology, prior diagnoses and prior treatments.</p> <p>Results</p> <p>The majority (61%) of patients in this case series were diagnosed with early Lyme disease. Of those diagnosed with early Lyme disease, 13% did not present with erythema migrans; of those not presenting with a rash, 54% had been previously misdiagnosed. Among those with a rash, the diagnosis of erythema migrans was initially missed in 23% of patients whose rash was subsequently confirmed. Of all patients previously misdiagnosed, 41% had received initial antibiotics likely to be ineffective against Lyme disease.</p> <p>Conclusion</p> <p>For community physicians practicing in high-risk geographic areas, the diagnosis of Lyme disease remains a challenge. Failure to recognize erythema migrans or alternatively, viral-like presentations without a rash, can lead to missed or delayed diagnosis of Lyme disease, ineffective antibiotic treatment, and the potential for late manifestations.</p

Decreased Th1-Type Inflammatory Cytokine Expression in the Skin Is Associated with Persisting Symptoms after Treatment of Erythema Migrans

Background: Despite the good prognosis of erythema migrans (EM), some patients have persisting symptoms of various character and duration post-treatment. Several factors may affect the clinical outcome of EM, e. g. the early interaction between Borrelia (B.) burgdorferi and the host immune response, the B. burgdorferi genotype, antibiotic treatment as well as other clinical circumstances. Our study was designed to determine whether early cytokine expression in the skin and in peripheral blood in patients with EM is associated with the clinical outcome. Methods: A prospective follow-up study of 109 patients with EM was conducted at the A land Islands, Finland. Symptoms were evaluated at 3, 6, 12 and 24 months post-treatment. Skin biopsies from the EM and healthy skin were immunohistochemically analysed for expression of interleukin (IL)-4, IL-10, IL-12p70 and interferon (IFN)-gamma, as well as for B. burgdorferi DNA. Blood samples were analysed for B. burgdorferi antibodies, allergic predisposition and levels of systemic cytokines. Findings: None of the patients developed late manifestations of Lyme borreliosis. However, at the 6-month follow-up, 7 of 88 patients reported persisting symptoms of diverse character. Compared to asymptomatic patients, these 7 patients showed decreased expression of the Th1-associated cytokine IFN-gamma in the EM biopsies (p = 0.003). B. afzelii DNA was found in 48%, B. garinii in 15% and B. burgdorferi sensu stricto in 1% of the EM biopsies, and species distribution was the same in patients with and without post-treatment symptoms. The two groups did not differ regarding baseline patient characteristics, B. burgdorferi antibodies, allergic predisposition or systemic cytokine levels. Conclusion: Patients with persisting symptoms following an EM show a decreased Th1-type inflammatory response in infected skin early during the infection, which might reflect a dysregulation of the early immune response. This finding supports the importance of an early, local Th1-type response for optimal resolution of LB.Original Publication: Johanna Sjöwall, Linda Fryland, Marika Nordberg, Florence Sjögren, Ulf Garpmo, Christian Jansson, Sten-Anders Carlsson, Sven Bergstrom, Jan Ernerudh, Dag Nyman, Pia Forsberg and Christina Ekerfelt, Decreased Th1-Type Inflammatory Cytokine Expression in the Skin Is Associated with Persisting Symptoms after Treatment of Erythema Migrans, 2011, PLOS ONE, (6), 3, 0018220. http://dx.doi.org/10.1371/journal.pone.0018220 Copyright: Public Library of Science (PLoS) http://www.plos.org

Respiratory failure presenting in H1N1 influenza with Legionnaires disease: two case reports

<p>Abstract</p> <p>Introduction</p> <p>Media sensationalism on the H1N1 outbreak may have influenced decisional processes and clinical diagnosis.</p> <p>Case Presentation</p> <p>We report two cases of patients who presented in 2009 with coexisting H1N1 virus and Legionella infections: a 69-year-old Caucasian man and a 71-year-old Caucasian woman. In our cases all the signs and symptoms, including vomiting, progressive respiratory disease leading to respiratory failure, refractory hypoxemia, leukopenia, lymphopenia, thrombocytopenia, and elevated levels of creatine kinase and hepatic aminotransferases, were consistent with critical illness due to 2009 H1N1 virus infection. Other infectious disorders may mimic H1N1 viral infection especially Legionnaires' disease. Because the swine flu H1N1 pandemic occurred in Autumn in Italy, Legionnaires disease was to be highly suspected since the peak incidence usually occurs in early fall. We do think that our immediate suspicion of Legionella infection based on clinical history and X-ray abnormalities was fundamental for a successful resolution.</p> <p>Conclusion</p> <p>Our two case reports suggest that patients with H1N1 should be screened for Legionella, which is not currently common practice. This is particularly important since the signs and symptoms of both infections are similar.</p

Borrelia Burgdorferi Induces a Type I Interferon Response During Early Stages of Disseminated Infection in Mice

BACKGROUND: Lyme borrelia genotypes differ in their capacity to cause disseminated disease. Gene array analysis was employed to profile the host transcriptome induced by Borrelia burgdorferi strains with different capacities for causing disseminated disease in the blood of C3H/HeJ mice during early infection. RESULTS: B. burgdorferi B515, a clinical isolate that causes disseminated infection in mice, differentially regulated 236 transcripts (P \u3c 0.05 by ANOVA, with fold change of at least 2). The 216 significantly induced transcripts included interferon (IFN)-responsive genes and genes involved in immunity and inflammation. In contrast, B. burgdorferi B331, a clinical isolate that causes transient skin infection but does not disseminate in C3H/HeJ mice, stimulated changes in only a few genes (1 induced, 4 repressed). Transcriptional regulation of type I IFN and IFN-related genes was measured by quantitative RT-PCR in mouse skin biopsies collected from the site of infection 24 h after inoculation with B. burgdorferi. The mean values for transcripts of Ifnb, Cxcl10, Gbp1, Ifit1, Ifit3, Irf7, Mx1, and Stat2 were found to be significantly increased in B. burgdorferi strain B515-infected mice relative to the control group. In contrast, transcription of these genes was not significantly changed in response to B. burgdorferi strain B331 or B31-4, a mutant that is unable to disseminate. CONCLUSIONS: These results establish a positive association between the disseminating capacity of B. burgdorferi and early type I IFN induction in a murine model of Lyme disease

Immunoblot analysis of the seroreactivity to recombinant Borrelia burgdorferi sensu lato antigens, including VlsE, in the long-term course of treated patients with Erythema migrans

Objective: We evaluated whether immunoblotting is capable of substantiating the posttreatment clinical assessment of patients with erythema migrans ( EM), the hallmark of early Lyme borreliosis. Methods: In 50 patients, seroreactivity to different antigens of Borrelia burgdorferi sensu lato was analyzed by a recombinant immunoblot test (IB) in consecutive serum samples from a minimum follow-up period of 1 year. Antigens in the IgG test were decorin- binding protein A, internal fragment of p41 (p41i), outer surface protein C (OspC), p39, variable major protein-like sequence expressed (VlsE), p58 and p100; those in the IgM test were p41i, OspC and p39. Immune responses were correlated with clinical and treatment-related parameters. Results: Positive IB results were found in 50% before, in 57% directly after therapy and in 44% by the end of the follow-up for the IgG class, and in 36, 43 and 12% for the IgM class. In acute and convalescence phase sera, VlsE was most immunogenic on IgG testing 60 and 70%), and p41i (46 and 57%) and OspC (40 and 57%) for the IgM class. By the end of the follow-up, only the anti-p41i lgM response was significantly decreased to 24%. Conclusions: No correlation was found between IB results and treatment-related parameters. Thus, immunoblotting does not add to the clinical assessment of EM patients after treatment. Copyright (c) 2008 S. Karger AG, Basel

Health care costs, utilization and patterns of care following Lyme disease

BACKGROUND:Lyme disease is the most frequently reported vector borne infection in the United States. The Centers for Disease Control have estimated that approximately 10% to 20% of individuals may experience Post-Treatment Lyme Disease Syndrome - a set of symptoms including fatigue, musculoskeletal pain, and neurocognitive complaints that persist after initial antibiotic treatment of Lyme disease. Little is known about the impact of Lyme disease or post-treatment Lyme disease symptoms (PTLDS) on health care costs and utilization in the United States. OBJECTIVES:1) to examine the impact of Lyme disease on health care costs and utilization, 2) to understand the relationship between Lyme disease and the probability of developing PTLDS, 3) to understand how PTLDS may impact health care costs and utilization. METHODS:This study utilizes retrospective data on medical claims and member enrollment for persons aged 0-64 years who were enrolled in commercial health insurance plans in the United States between 2006-2010. 52,795 individuals treated for Lyme disease were compared to 263,975 matched controls with no evidence of Lyme disease exposure. RESULTS:Lyme disease is associated with $2,968 higher total health care costs (95$3,798 higher total health care costs (95% CI: 3,542-4,055, p<.001) and 66% more outpatient visits (95% CI: 64%-69%, p<.001) over a 12-month period, relative to those with no PTLDS-related diagnoses. CONCLUSIONS:Lyme disease is associated with increased costs above what would be expected for an easy to treat infection. The presence of PTLDS-related diagnoses after treatment is associated with significant health care costs and utilization