2009 Lyme & TBD Abstracts  - ARCHIVE

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Cent Eur J Public Health. 2009 Dec;17(4):179-82.

Direct detection of Borrelia burgdorferi spirochetes in patients with early disseminated Lyme borreliosis.
Schwarzová K, Kost'anová Z, Holecková K, Spitalská E, Boldis V.

Institute of Virology, Slovak Academy of Sciences, Bratislava. virukats@savba.sk

The detection of spirochetes in 15 patients with clinically documented early disseminated LB has been analysed when using cultivation method of the plasma or the cerebrospinal fluid, electron microscopy, commercial Western blot and detecting the DNA of the pathogen in vitro cultures by PCR-RFLP. Spirochetes were isolated in eight blood and one cerebrospinal fluid culture samples. In seven cases (47%), previous serodiagnostic laboratory tests were negative. Borrelial DNA was detected by PCR in 67% patients (9 blood samples and 1 CSF sample). Using Msel restriction fragments of PCR products of the amplified rrf-rrl region, we identified Borrelia garinii (80%), one B. afzelii isolate and one B. burgdorferi s.s.

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J Econ Entomol. 2009 Dec; 102 (6):2316-24.

Ability of two natural products, nootkatone and carvacrol, to suppress Ixodes scapularis and Amblyomma americanum (Acari: Ixodidae) in a Lyme disease endemic area of New Jersey.
Dolan MC, Jordan RA, Schulze TL, Schulze CJ, Manning MC, Ruffolo D, Schmidt JP, Piesman J, Karchesy JJ.

Division of Vector-Borne Infectious Diseases, National Center for Zoonotic, Vector-Borne and Enteric Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USA. mat.pound@ars.usda.gov

We evaluated the ability of the natural, plant-derived acaricides nootkatone and carvacrol to suppress Ixodes scapularis Say and Amblyomma americanum (L.) (Acari: Ixodidae). Aqueous formulations of 1 and 5% nootkatone applied by backpack sprayer to the forest litter layer completely suppressed I. scapularis nymphs through 2 d. Thereafter, the level of reduction gradually declined to < or =50% at 28 d postapplication. Against A. americanum nymphs, 1% nootkatone was less effective, but at a 5% concentration, the level of control was similar or greater to that observed with I. scapularis through 21 d postapplication. Initial applications of 0.05% carvacrol were ineffective, but a 5% carvacrol formulation completely suppressed nymphs of both species through 2 d and resulted in significant reduction in I. scapularis and A. americanum nymphs through 28 and 14 d postapplication, respectively. Backpack sprayer applications of 5% nootkatone to the shrub and litter layers resulted in 100% control of I. scapularis adults through 6 d, but the level of reduction declined to 71.5% at 28 d postapplication. By contrast, high-pressure applications of 2% nootkatone to the litter layer resulted in 96.2-100% suppression of both I. scapularis and A. americanum nymphs through 42 d, whereas much lower control was obtained from the same formulation applied by backpack sprayer. Backpack sprayer application of a 3.1% nootkatone nanoemulsion resulted in 97.5-98.9 and 99.3-100% reduction in I. scapularis and A. americanum nymphs, respectively, at 1 d postapplication. Between 7 d and 35 d postapplication, the level of control varied between 57.1% and 92.5% for I. scapularis and between 78.5 and 97.1% for A. americanum nymphs. The ability of natural products to quickly suppress and maintain significant control of populations of these medically important ticks at relatively low concentrations may represent a future alternative to the use of conventional synthetic acaricides.

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Arthritis Rheum. 2009 Dec;60(12):3831-40.

HLA-DR alleles determine responsiveness to Borrelia burgdorferi antigens in a mouse model of self-perpetuating arthritis.

Iliopoulou BP, Guerau-de-Arellano M, Huber BT.

Tufts University, Boston, Massachusetts 02111, USA.

OBJECTIVE: Arthritis is a prominent manifestation of Lyme disease, which is caused by infection with Borrelia burgdorferi (Bb). Chronic Lyme arthritis persisting even after antibiotic treatment is linked to HLA-DRB1*0401 (DR4) and related alleles. In contrast, patients whose Lyme arthritis resolves within 3 months postinfection show an increased frequency of HLA-DRB1*1101 (DR11). The aim of this study was to analyze the underlying mechanism by which HLA-DR alleles confer genetic susceptibility or resistance to antibiotic-refractory Lyme arthritis. METHODS: We generated DR11-transgenic (DR11-Tg) mice on a murine MHCII-/- background and compared their immune response to Bb antigens with the response of DR4-Tg mice after immunization with Bb outer surface protein A (OspA) or infection with live Bb. RESULTS: T cells from OspA-immunized and Bb-infected DR11-Tg mice had defective production of interferon-gamma as compared with those from DR4-Tg mice. In contrast, DR11-Tg mice developed higher titers of anti-OspA and anti-Bb antibodies, respectively, than did DR4-Tg mice. Consistent with this observation, we found that the Bb-infected DR11-Tg mice had a decreased spirochetal burden as compared with the DR4-Tg mice, as measured by quantitative polymerase chain reaction. CONCLUSION: This study provides direct evidence that in the presence of HLA-DR11, the immune response against Bb antigens is directed toward a protective antibody response. In contrast, an inflammatory Th1 response is induced in the presence of DR4. These observations offer an explanation for the differential genetic susceptibility of DR4+ and DR11+ individuals to the development of chronic Lyme arthritis and, eventually, the progression to antibiotic-refractory Lyme arthritis.

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Proc Biol Sci. 2009 Nov 22;276(1675):3911-9. Epub 2009 Aug 19.

Hosts as ecological traps for the vector of Lyme disease.
Keesing F, Brunner J, Duerr S, Killilea M, Logiudice K, Schmidt K, Vuong H, Ostfeld RS.

Department of Biology, Bard College, Annandale, NY 12504, USA. keesing@bard.edu.

Vectors of infectious diseases are generally thought to be regulated by abiotic conditions such as climate or the availability of specific hosts or habitats. In this study we tested whether blacklegged ticks, the vectors of Lyme disease, granulocytic anaplasmosis and babesiosis can be regulated by the species of vertebrate hosts on which they obligately feed. By subjecting field-caught hosts to parasitism by larval blacklegged ticks, we found that some host species (e.g. opossums, squirrels) that are abundantly parasitized in nature kill 83-96% of the ticks that attempt to attach and feed, while other species are more permissive of tick feeding. Given natural tick burdens we document on these hosts, we show that some hosts can kill thousands of ticks per hectare. These results indicate that the abundance of tick vectors can be regulated by the identity of the hosts upon which these vectors feed. By simulating the removal of hosts from intact communities using empirical models, we show that the loss of biodiversity may exacerbate disease risk by increasing both vector numbers and vector infection rates with a zoonotic pathogen.

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Cell Host Microbe. 2009 Nov 19;6(5):482-92.

Antibodies against a Tick Protein, Salp15, Protect Mice from the Lyme Disease Agent.
Dai J, Wang P, Adusumilli S, Booth CJ, Narasimhan S, Anguita J, Fikrig E.

Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.

Traditionally, vaccines directly target a pathogen or microbial toxin. Lyme disease, caused by Borrelia burgdorferi, is a tick-borne illness for which a human vaccine is not currently available. B. burgdorferi binds a tick salivary protein, Salp15, during transmission from the vector, and this interaction facilitates infection of mice. We now show that Salp15 antiserum significantly protected mice from B. burgdorferi infection. Salp15 antiserum also markedly enhanced the protective capacity of antibodies against B. burgdorferi antigens, such as OspA or OspC. Mice actively immunized with Salp15 were also significantly protected from tick-borne Borrelia. In vitro assays showed that Salp15 antiserum increased the clearance of Salp15-coated B. burgdorferi by phagocytes, suggesting a mechanism of action. Vaccination with a vector molecule that a microbe requires for infection of the mammalian host suggests a new strategy for the prevention of Lyme disease, and this paradigm may be applicable to numerous arthropod-borne pathogens of medical importance.

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MMWR Morb Mortal Wkly Rep. 2009 Sep 25;58(37):1033-6.

Anaplasmosis and ehrlichiosis - Maine, 2008.
Centers for Disease Control and Prevention (CDC).

Anaplasmosis and ehrlichiosis are rickettsial tickborne diseases that have had at least a twofold increase in prevalence in the United States since 2000. Despite similar clinical presentations, the causative organisms are carried by different ticks with distinct geographic and ecologic associations. Surveillance efforts are complicated by ambiguous terminology and serologic testing with antibody cross-reactivity. Although anaplasmosis historically has been reported in Maine, ehrlichiosis has been reported infrequently. During 2007-2008, the number of physician-reported anaplasmosis cases nearly doubled in Maine, and ehrlichiosis cases increased more than fourfold. To examine this increase, the Maine Department of Health and Human Services (MDHHS) analyzed available data on tick burden and physician-reported cases of anaplasmosis and ehrlichiosis during 2000-2008. This report describes the results of that analysis, which indicated that Ixodes scapularis (the tick vector for Anaplasma phagocytophilum) was broadly distributed in Maine, whereas Amblyomma americanum (the tick vector for Erhlichia chaffeenisis) was scarce. Moreover, 95% of physician-reported ehrlichiosis cases lacked a concurrent serologic assessment to exclude anaplasmosis, suggesting that antibody cross-reactivity might have resulted in misclassification. In 2008, Maine modified case classification to enhance specificity; ehrlichiosis cases that lack a concurrent test for anaplasmosis are now classified as suspect rather than probable and therefore are not included in national surveillance summaries. The accuracy of case classification and surveillance can be improved by educating health-care providers regarding 1) the expected geographic distribution of tick vectors and 2) recommendations for confirmatory testing to distinguish between the causative organisms of anaplasmosis and ehrlichiosis.

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Pediatr Dermatol. 2009 Sep-Oct;26(5):635-6.

Lyme Disease as a Cause of Acropapular Dermatitis of Childhood.
Kennedy CE, Azfar RS, Honig PJ.

Department of Medicine, University of California, San Diego, USA.

Acropapular dermatitis of childhood is a symmetric self-limited papulovesicular exanthem that classically occurs on the cheeks, extensor extremities, and buttocks in young children. The eruption of acropapular dermatitis of childhood represents a reaction to a variety of infections usually of viral origin. We present a child with typical findings of acropapular dermatitis of childhood whose serologic workup revealed an acute Lyme infection.

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J Med Entomol.2009 May; 46(3):557-65.

Isolation of Entomopathogenic Fungi From Soils and Ixodes scapolaris (Acari: Ixodidae) Ticks: Prevalence and Methods.
Tuininga AR, Miller JL, Morath SU, Daniels TJ, Falco RC, Marchese M, Sahabi S, Rosa D, Stafford KC 3rd.

Fordham University, Louis Calder Center and Department of Biological Sciences, Armonk, NY 10504, USA. tuininga@fordham.edu

Entomopathogenic fungi are commonly found in forested soils that provide tick habitat, and many species are pathogenic to Ixodes scapularis Say, the blacklegged tick. As a first step to developing effective biocontrol strategies, the objective of this study was to determine the best methods to isolate entomopathogenic fungal species from field-collected samples of soils and ticks from an Eastern deciduous forest where I. scapularis is common. Several methods were assessed: (1) soils, leaf litter, and ticks were plated on two types of media; (2) soils were assayed for entomopathogenic fungi using the Galleria bait method; (3) DNA from internal transcribed spacer (ITS) regions of the nuclear ribosomal repeat was extracted from pure cultures obtained from soils, Galleria, and ticks and was amplified and sequenced; and (4) DNA was extracted directly from ticks, amplified, and sequenced. We conclude that (1) ticks encounter potentially entomopathogenic fungi more often in soil than in leaf litter, (2) many species of potentially entomopathogenic fungi found in the soil can readily be cultured, (3) the Galleria bait method is a sufficiently efficient method for isolation of these fungi from soils, and (4) although DNA extraction from ticks was not possible in this study because of small sample size, DNA extraction from fungi isolated from soils and from ticks was successful and provided clean sequences in 100 and 73% of samples, respectively. A combination of the above methods is clearly necessary for optimal characterization of entomopathogenic fungi associated with ticks in the environment.

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N Engl J Med. 2009 May 14;360(20):2099-107.

Fatal case of deer tick virus encephalitis.
Tavakoli NP, Wang H, Dupuis M, Hull R, Ebel GD, Gilmore EJ, Faust PL.

C Wadsworth Center, New York State Department of Health and the Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, New York, USA. norma.tavakoli@wadsworth.org

Deer tick virus is related to Powassan virus, a tickborne encephalitis virus. A 62-year-old man presented with a meningoencephalitis syndrome and eventually died. Analyses of tissue samples obtained during surgery and at autopsy revealed a widespread necrotizing meningoencephalitis. Nucleic acid was extracted from formalin-fixed tissue, and the presence of deer tick virus was verified on a flavivirus-specific polymerase-chain-reaction (PCR) assay, followed by sequence confirmation. Immunohistochemical analysis with antisera specific for deer tick virus identified numerous immunoreactive neurons, with prominent involvement of large neurons in the brain stem, cerebellum, basal ganglia, thalamus, and spinal cord. This case demonstrates that deer tick virus can be a cause of fatal encephalitis. 2009 Massachusetts Medical Society

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Vector Borne Zoonotic Dis. 2009 Sep 2. (Epub ahead of print).

Assessment of Polymicrobial Infections in Ticks in New York State.
Tokarz R, Jain K, Bennett A, Briese T, Ian Lipkin W.

Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY.

Ixodes scapularis ticks are clinically important hematophagous vectors. A single tick bite can lead to a polymicrobial infection. We determined the prevalence of polymicrobial infection with Borrelia burgdorferi, Anaplasma phagocytophilum, Babesia microti, Borrelia miyamotoi, and Powassan virus in 286 adult ticks from the two counties in New York State where Lyme disease is endemic, utilizing a MassTag multiplex polymerase chain reaction assay. Seventy-one percent of the ticks harbored at least one organism; 30% had a polymicrobial infection. Infections with three microbes were detected in 5% of the ticks. One tick was infected with four organisms. Our results show that coinfection is a frequent occurrence in ticks in the two counties surveyed.

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Vector Borne Zoonotic Dis. 2009 Aug;9(4):439-48.

The United States Department of Agriculture's Northeast Area-wide Tick Control Project: summary and conclusions.
Pound JM, Miller JA, George JE, Fish D, Carroll JF, Schulze TL, Daniels TJ, Falco RC, Stafford KC, Mather TN.

Knipling-Bushland U.S. Livestock Insects Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Kerrville, Texas 78028-9184, USA.  mat.pound@ars.usda.gov

From 1997 to 2002, the U.S. Department of Agriculture's Northeast Area-wide Tick Control Project used acaricide-treated 4-Poster Deer Treatment Bait Stations in five eastern states to control ticks feeding on white-tailed deer. The objectives of this host-targeted technology were to reduce free-living blacklegged (Ixodes scapularis Say) and lone star (Amblyomma americanum [L.]) tick populations and thereby to reduce the risk of tick-borne disease. During 2002 to 2004, treatments were suspended, and tick population recovery rates were assayed. Subsequently, the major factors that influenced variations in efficacy were extrapolated to better understand and improve this technology. Treatments resulted in significant reductions in free-living populations of nymphal blacklegged ticks at six of the seven sites, and lone star ticks were significantly reduced at all three sites where they were present. During the study, maximal significant (p < or = 0.05) efficacies against nymphal blacklegged and lone star ticks at individual sites ranged from 60.0 to 81.7 and 90.9 to 99.5%, respectively. The major environmental factor that reduced efficacy was the occurrence of heavy acorn masts, which provided an alternative food resource for deer. Although the 4-Poster technology requires 1 or more years to show efficacy, this host-targeted intervention was demonstrated to be an efficacious, economical, safe, and environment-friendly alternative to area-wide spraying of acaricide to control free-living populations of these tick species.

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Vector Borne Zoonotic Dis. 2009 Aug;9(4):423-30.

Evaluation of the United States Department of Agriculture Northeast Area-wide Tick Control Project by meta-analysis.
Brei B, Brownstein JS, George JE, Pound JM, Miller JA, Daniels TJ, Falco RC, Stafford KC 3rd, Schulze TL, Mather TN, Carroll JF, Fish D.

Department of Epidemiology and Public Health, Yale School of Medicine, New Haven, Connecticut, USA.

As part of the Northeast Area-wide Tick Control Project (NEATCP), meta-analyses were performed using pooled data on the extent of tick-vector control achieved through seven concurrent studies, conducted within five states, using U.S. Department of Agriculture "4-Poster" devices to deliver targeted-acaricide to white-tailed deer. Although reductions in the abundance of all life-stages of Ixodes scapularis were the measured outcomes, this study focused on metrics associated with I. scapularis nymphal tick densities as this measure has consistently proven to directly correlate with human risk of acquiring Lyme disease. Since independent tick sampling schemes were undertaken at each of the five environmentally distinct study locations, a meta-analytic approach permitted estimation of a single true control-effect size for each treatment year of the NEATCP. The control-effect is expressed as the annual percent I. scapularis nymphal control most consistent with meta-analysis data for each treatment year. Our meta-analyses indicate that by the sixth treatment year, the NEATCP effectively reduced the relative density of I. scapularis nymphs by 71% on the 5.14 km(2) treatment sites, corresponding to a 71% lower relative entomologic risk index for acquiring Lyme disease.

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J Neuroinflammation.  2009 Aug 25;6:23.  

Possible role of glial cells in the onset and progression of Lyme neuroborreliosis.
Ramesh G, Borda JT, Gill A, Ribka EP, Morici LA, Mottram P, Martin DS, Jacobs MB, Didier PJ, Philipp MT.

Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Covington, LA, USA. gramesh@tulane.edu

BACKGROUND: Lyme neuroborreliosis (LNB) may present as meningitis, cranial neuropathy, acute radiculoneuropathy or, rarely, as encephalomyelitis. We hypothesized that glia, upon exposure to Borrelia burgdorferi, the Lyme disease agent, produce inflammatory mediators that promote the acute cellular infiltration of early LNB. This inflammatory context could potentiate glial and neuronal apoptosis. METHODS: We inoculated live B. burgdorferi into the cisterna magna of rhesus macaques and examined the inflammatory changes induced in the central nervous system (CNS), and dorsal root nerves and ganglia (DRG). RESULTS: ELISA of the cerebrospinal fluid (CSF) showed elevated IL-6, IL-8, CCL2, and CXCL13 as early as one week post-inoculation, accompanied by primarily lymphocytic and monocytic pleocytosis. In contrast, onset of the acquired immune response, evidenced by anti-B. burgdorferi C6 serum antibodies, was first detectable after 3 weeks post-inoculation. CSF cell pellets and CNS tissues were culture-positive for B. burgdorferi. Histopathology revealed signs of acute LNB: severe multifocal leptomeningitis, radiculitis, and DRG inflammatory lesions. Immunofluorescence staining and confocal microscopy detected B. burgdorferi antigen in the CNS and DRG. IL-6 was observed in astrocytes and neurons in the spinal cord, and in neurons in the DRG of infected animals. CCL2 and CXCL13 were found in microglia as well as in endothelial cells, macrophages and T cells. Importantly, the DRG of infected animals showed significant satellite cell and neuronal apoptosis. CONCLUSION: Our results support the notion that innate responses of glia to B. burgdorferi initiate/mediate the inflammation seen in acute LNB, and show that neuronal apoptosis occurs in this context.

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Pediatrics. 2009 May;123(5):e835-41.

Lyme carditis in children: presentation, predictive factors, and clinical course.
Costello JM, Alexander ME, Greco KM, Perez-Atayde AR, Laussen PC.

Harvard Medical School, Division of Cardiac Intensive Care, Department of Cardiology, Children's Hospital Boston, 300 Longwood Ave, Bader 600, Boston, MA 02115, USA. john.costello@cardio.chboston.org

OBJECTIVES: We sought to identify predictive factors for Lyme carditis in children and to characterize the clinical course of these patients. METHODS: We reviewed all cases of early disseminated Lyme disease presenting to our institution from January 1994 through July 2008, and summarized the presentation and course of those patients with carditis. A case-control study was used to identify predictive factors for carditis. Controls were patients with early disseminated Lyme disease without carditis. RESULTS: Of 207 children with early disseminated Lyme disease, 33 (16%) had carditis, 14 (42%) of whom had advanced heart block, including 9 (27%) with complete heart block. The median time to recovery of sinus rhythm in these 14 patients was 3 days (range: 1-7 days), and none required a permanent pacemaker. Four (12%) of 33 patients with carditis had depressed ventricular systolic function, 3 (9%) of whom required mechanical ventilation, temporary pacing, and inotropic support. Complete resolution of rhythm disturbances and myocardial dysfunction occurred in 24 (89%) of 27 patients for whom follow-up data were available. Most patients with carditis also had other systemic Lyme involvement. By using multivariate logistic regression analysis, we found that children >10 years of age, those with arthralgias, and those with cardiopulmonary symptoms were more likely to have carditis. CONCLUSIONS: The spectrum of presentation for children with Lyme carditis is broad, ranging from asymptomatic, first-degree heart block to fulminant myocarditis. Variable degrees of heart block are the most common manifestation and occasionally require temporary pacing. Transient myocardial dysfunction, although less common, can be life-threatening. Advanced heart block resolves within 1 week in most cases. In children with early disseminated Lyme disease, older age, arthralgias, and cardiopulmonary symptoms independently predict the presence of carditis.

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Pediatrics. 2009 May;123(5):e829-34.

Prospective validation of a clinical prediction model for Lyme meningitis in children.
Garro AC, Rutman M, Simonsen K, Jaeger JL, Chapin K, Lockhart G.

Rhode Island Hospital, Pediatric Emergency Medicine, Claverick Building, 2nd Floor, Providence, RI 02906, USA. agarro@lifespan.org

OBJECTIVE: Lyme meningitis is difficult to differentiate from other causes of aseptic meningitis in Lyme disease-endemic regions. Parenteral antibiotics are indicated for Lyme meningitis but not viral causes of aseptic meningitis. A clinical prediction model was developed to distinguish Lyme meningitis from other causes of aseptic meningitis. Our objective was to prospectively validate this model. METHODS: Children between 2 and 18 years of age presenting to Hasbro Children's Hospital from April through October of 2006 and 2007 were enrolled if a lumbar puncture for meningitis showed a cerebrospinal fluid white blood cell count of >8 cells per microL. Cerebrospinal fluid was sent for Lyme antibody testing. The probability of Lyme meningitis was calculated by using the percentage of cerebrospinal fluid mononuclear cells, duration of headache, and presence of cranial neuropathy by using the prediction model. Definite Lyme meningitis cases were defined as cerebrospinal fluid pleocytosis with (1) positive Lyme serology confirmed by immunoblot or (2) erythema migrans rash. Possible Lyme meningitis cases were defined as cerebrospinal fluid pleocytosis with positive cerebrospinal fluid Lyme antibody. Sensitivity, specificity, and likelihood ratios for definite and possible Lyme meningitis were determined by using 10% increments of calculated probability of Lyme meningitis. RESULTS: Fifty children were enrolled, including 14 children with definite Lyme meningitis, 6 with possible Lyme meningitis, and 30 with aseptic meningitis. A calculated probability of <10% for Lyme meningitis had a negative likelihood ratio of 0.006 for definite and possible Lyme meningitis cases. A calculated probability of >50% for Lyme meningitis had a positive likelihood ratio of 100 using these definitions. CONCLUSIONS: A clinical prediction model using the percentage of cerebrospinal fluid mononuclear cells, headache duration, and presence of cranial neuropathy can differentiate children with Lyme meningitis from children with aseptic meningitis. Our findings suggest categories of low (<10%), indeterminate (10%-50%), and high (>50%) probability of Lyme meningitis.

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Arch Gen Psychiatry. 2009;66(5):554-563.

Regional Cerebral Blood Flow and Metabolic Rate in Persistent Lyme Encephalopathy.
Fallon BA, Lipkin RB, Corbera KM, Yu S, Nobler MS, Keilp JG, Petkova E, Lisanby SH, Moeller JR, Slavov I, Van Heertum R, Mensh BD, Sackeim, HA.

Columbia University, 1051 Riverside Drive, Unit 69, New York, NY 10032, USA. baf1@columbia.edu

Context  There is controversy regarding whether objective neurobiological abnormalities exist after intensive antibiotic treatment for Lyme disease.   Objectives  To determine whether patients with a history of well-characterized Lyme disease and persistent cognitive deficit show abnormalities in global or topographic distributions of regional cerebral blood flow (rCBF) or cerebral metabolic rate (rCMR).

Design  Case-controlled study.  Setting  A university medical center.  Participants  A total of 35 patients and 17 healthy volunteers (controls). Patients had well-documented prior Lyme disease, a currently reactive IgG Western blot, prior treatment with at least 3 weeks of intravenous cephalosporin, and objective memory impairment.  Main Outcome Measures  Patients with persistent Lyme encephalopathy were compared with age-, sex-, and education-matched controls. Fully quantified assessments of rCBF and rCMR for glucose were obtained while subjects were medication-free using positron emission tomography. The CBF was assessed in 2 resting room air conditions (without snorkel and with snorkel) and 1 challenge condition (room air enhanced with carbon dioxide, ie, hypercapnia). Results  Statistical parametric mapping analyses revealed regional abnormalities in all rCBF and rCMR measurements that were consistent in location across imaging methods and primarily reflected hypoactivity. Deficits were noted in bilateral gray and white matter regions, primarily in the temporal, parietal, and limbic areas. Although diminished global hypercapnic CBF reactivity (< .02) was suggestive of a component of vascular compromise, the close coupling between CBF and CMR suggests that the regional abnormalities are primarily metabolically driven. Patients did not differ from controls on global resting CBF and CMR measurements. Conclusions  Patients with persistent Lyme encephalopathy have objectively quantifiable topographic abnormalities in functional brain activity. These CBF and CMR reductions were observed in all measurement conditions. Future research should address whether this pattern is also seen in acute neurologic Lyme disease.

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J Infect Dis. 2009 May 1;199(9):1379-88.

The Antibiotics Doxycycline and Minocycline Inhibit the Inflammatory Responses to the Lyme Disease Spirochete Borrelia burgdorferi.
Bernardino AL, Kaushal D, Philipp MT.

Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University, Covington, Louisiana.

Tetracyclines moderate inflammatory responses of various etiologies. We hypothesized that tetracyclines, in addition to their antimicrobial function, could exert control over the inflammation elicited by Borrelia burgdorferi. To model systemic effects, we used the human monocytic cell line THP-1; to model effects in the central nervous system, we used rhesus monkey brain astrocytes and microglia. Cells were stimulated with live or sonicated B. burgdorferi or with the lipoprotein outer surface protein A in the presence of increasing concentrations of doxycycline or minocycline. Both antibiotics significantly reduced the production of tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8 in a dose-dependent manner in all cell types. Microarray analyses of the effect of doxycycline on gene transcription in spirochete-stimulated monocytes revealed that the NFKB and CHUK (alias, IKKA) genes were down-regulated. Functionally, phosphorylation of IkappaBalpha and binding of NF-kappaB to target DNA were both reduced in these cells. Our results suggest that tetracyclines may have a dual therapeutic effect in Lyme disease.

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Arthritis Rheum. 2009 Apr;60(4):1179-86.

HLA type and immune response to Borrelia burgdorferi outer surface protein a in people in whom arthritis developed after Lyme disease vaccination.
Ball R, Shadomy SV, Meyer A, Huber BT, Leffell MS, Zachary A, Belotto M, Hilton E, Bryant-Genevier M, Schriefer ME, Miller FW, Braun MM.

Center for Biologics Evaluation and Research, FDA, Rockville, Maryland, USA. Robert.Ball@fda.hhs.gov

OBJECTIVE: To investigate whether persons with treatment-resistant Lyme arthritis-associated HLA alleles might develop arthritis as a result of an autoimmune reaction triggered by Borrelia burgdorferi outer surface protein A (OspA), the Lyme disease vaccine antigen. METHODS: Persons in whom inflammatory arthritis had developed after Lyme disease vaccine (cases) were compared with 3 control groups: 1) inflammatory arthritis but not Lyme disease vaccine (arthritis controls), 2) Lyme disease vaccine but not inflammatory arthritis (vaccine controls), and 3) neither Lyme disease vaccine nor inflammatory arthritis (normal controls). HLA-DRB1 allele typing, Western blotting for Lyme antigen, and T cell reactivity testing were performed. RESULTS: Twenty-seven cases were matched with 162 controls (54 in each control group). Odds ratios (ORs) for the presence of 1 or 2 treatment-resistant Lyme arthritis alleles were 0.8 (95% confidence interval [95% CI] 0.3-2.1), 1.6 (95% CI 0.5-4.4), and 1.75 (95% CI 0.6-5.3) in cases versus arthritis controls, vaccine controls, and normal controls, respectively. There were no significant differences in the frequency of DRB1 alleles. T cell response to OspA was similar between cases and vaccine controls, as measured using the stimulation index (OR 1.6 [95% CI 0.5-5.1]) or change in uptake of tritiated thymidine (counts per minute) (OR 0.7 [95% CI 0.2-2.3]), but cases were less likely to have IgG antibodies to OspA (OR 0.3 [95% CI 0.1-0.8]). Cases were sampled closer to the time of vaccination (median 3.59 years versus 5.48 years), and fewer cases had received 3 doses of vaccine (37% versus 93%). CONCLUSION: Treatment-resistant Lyme arthritis alleles were not found more commonly in persons who developed arthritis after Lyme disease vaccination, and immune responses to OspA were not significantly more common in arthritis cases. These results suggest that Lyme disease vaccine is not a major factor in the development of arthritis in these cases.

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Pediatrics. 2009 Mar;123(3):959-65.

Acute pediatric monoarticular arthritis: distinguishing lyme arthritis from other etiologies.
Thompson A, Mannix R, Bachur R.

Children's Hospital Boston, Division of Emergency Medicine, 300 Longwood Ave, Boston, MA 02115, USA. amy.thompson@childrens.harvard.edu

OBJECTIVE: Identify clinical predictors of Lyme arthritis among patients with acute monoarticular arthritis. METHODS: A medical chart review was conducted of children </=18 years of age with monoarticular arthritis who underwent arthrocentesis in a pediatric emergency department located in the northeast United States. Patients were classified into 3 categories of arthritis: septic, Lyme, or nonseptic non-Lyme arthritis. Historical, clinical, and laboratory data were compared to identify distinguishing features of Lyme arthritis. RESULTS: One hundred seventy-nine patients were studied: 46 (26%) patients with septic arthritis, 55 (31%) patients with Lyme arthritis, and 78 (43%) patients with nonseptic non-Lyme arthritis. Compared with those with septic arthritis, patients with Lyme disease were more likely to have a tick-bite history, knee involvement, and less likely to have a history of fever or elevated temperature at triage. Erythrocyte sedimentation rate, C-reactive protein, joint white blood cell count, and joint neutrophil percentage were also statistically lower. In comparison to nonseptic non-Lyme arthritis, knee involvement and tick-bite history were predictors of Lyme. Erythrocyte sedimentation rate, joint white blood cell count, and joint neutrophil percentage were also statistically different. Multivariate analysis comparing Lyme to septic arthritis demonstrated fever history and elevated C-reactive protein level to be negative predictors of Lyme arthritis and knee involvement to be a positive predictor (model sensitivity: 88%; specificity: 82%). CONCLUSIONS: Lyme arthritis shares features with both septic and nonseptic non-Lyme arthritis. This overlap prevents the creation of a clinically useful predictive model for Lyme arthritis. In endemic areas, Lyme testing should be performed on all patients presenting with acute monoarticular arthritis.

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Scand J Immunol. 2009 Jan;69(1):64-9.

Complement split products c3a and c4a in chronic lyme disease.
Stricker RB, Savely VR, Motanya NC, Giclas PC.

International Lyme and Associated Diseases Society, Bethesda, MD, USA. rstricker@usmamed.com

Complement split products C3a and C4a are reportedly elevated in patients with acute Lyme disease. We have now examined these immunologic markers in patients with chronic Lyme disease compared to appropriate disease controls. The study population consisted of 29 healthy controls, 445 patients with chronic Lyme disease, 11 patients with systemic lupus erythematosus (SLE) and six patients with AIDS. The Lyme disease patients were divided according to predominant musculoskeletal symptoms (324 patients) or predominant neurologic symptoms (121 patients). C3a and C4a levels were measured by radioimmunoassay. All patients with chronic Lyme disease and AIDS had normal C3a levels compared to controls, whereas patients with SLE had significantly increased levels of this marker. Patients with predominant musculoskeletal symptoms of Lyme disease and AIDS patients had significantly increased levels of C4a compared to either controls, patients with predominant neurologic symptoms of Lyme disease or SLE patients. Response to antibiotic therapy in chronic Lyme disease was associated with a significant decrease in the C4a level, whereas lack of response was associated with a significant increase in this marker. In contrast, AIDS patients had persistently increased C4a levels despite antiretroviral therapy. Lyme patients with positive single-photon emission computed tomographic (SPECT) scans had significantly lower C4a levels compared to Lyme patients with normal SPECT scan results. Patients with predominant musculoskeletal symptoms of Lyme disease have normal C3a and increased C4a levels. This pattern differs from the increase in both markers seen in acute Lyme disease, and C4a changes correlate with the response to therapy in chronic Lyme disease. C4a appears to be a valuable immunologic marker in patients with persistent symptoms of Lyme disease.

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J Med Entomol. 2009 Jan;46(1):131-8.

Detection of Borrelia burgdorferi and Borrelia lonestari in birds in Tennessee.
Jordan BE, Onks KR, Hamilton SW, Hayslette SE, Wright SM.

University of Tennessee Health Science Center, Memphis, TN 38163, USA.

Lyme disease in the United States is caused by the bacterial spirochete Borrelia burgdorferi s.s. (Johnson, Schmid, Hyde, Steigerwalt, and Brenner), which is transmitted by tick vectors Ixodes scapularis (Say) and I. pacificus (Cooley and Kohls). Borrelia lonestari, transmitted by the tick Amblyomma americanum L., may be associated with a related syndrome, southern tick-associated rash illness (STARI). Borrelia lonestari sequences, reported primarily in the southeastern states, have also been detected in ticks in northern states. It has been suggested that migratory birds may have a role in the spread of Lyme disease spirochetes. This study evaluated both migratory waterfowl and nonmigratory wild turkeys (Meleagris gallopavo silvestris, Eastern wild turkey) for B. burgdorferi and B. lonestari DNA sequences. A total of 389 avian blood samples (163 migratory birds representing six species, 125 wild turkeys harvested in habitats shared with migratory birds, 101 wild turkeys residing more distant from migratory flyways) were extracted, amplified, and probed to determine Borrelia presence and species identity. Ninety-one samples were positive for Borrelia spp. Among migratory birds and turkeys collected near migration routes, B. burgdorferi predominated. Among turkeys residing further away from flyways, detection of B. lonestari was more common. All A. americanum ticks collected from these areas were negative for Borrelia DNA; no I. scapularis were found. To our knowledge, this represents the first documentation of B. lonestari among any birds.

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