Diagnostik og behandling af Lyme neuroborreliose (2021)
Denne vejledning er tiltænkt diagnostik og behandling af formodet Lyme neuroborreliose hos voksne. Vejledningen er udarbejdet som et supplement til Borrelia klaringsrapport (2014).
148 KB, uploadet 10.11.2021
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Lumbalpunktur, blodfortyndende behandling og akut bakteriel meningitis (2019)
Rapport og anbefaling vedrørende ulemper og fordele ved henholdsvis at undlade eller gennemføre lumbalpunktur for patienter i blodfortyndende behandling mistænkt for akut bakteriel meningitis.
880 KB, uploadet 13.05.2021
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Encefalitis 2018
Arbejdsgruppe: Anne-Mette Lebech, Birgitte Rønde Hansen, Christian Brandt, Hans Rudolph von Lüttichau, Jacob Bodilsen, Jannick Helweg-Larsen, Lothar Wiese, Lykke Larsen, Trine Mogensen.
188 KB, uploadet 13.05.2021
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Viral meningitis (2018)
Udgiver: Dansk Selskab for Infektionsmedicin 2018
Arbejdsgruppe: Anne-Mette Lebech, Birgitte Rønde Hansen, Christian Brandt, Hans Rudolph von Lüttichau, Jacob Bodilsen, Jannik Helweg-Larsen, Lothar Wiese, Lykke Larsen, Trine Mogensen.
148 KB, uploadet 12.05.2021
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Akut bakteriel meningitis (2018)
Udgiver: Dansk Selskab for Infektionsmedicin
Arbejdsgruppe: Anne-Mette Lebech, Birgitte Rønde Hansen, Christian Brandt, Hans Rudolf von Lüttichau, Jacob Bodilsen, Lothar Wiese, Lykke Larsen, Trine Mogensen.
318 KB, uploadet 12.05.2021
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Borrelia klaringsrapport (2014)
Klinik, diagnostik og behandling af Lyme Borreliose i Danmark.
Forfattergruppen er nedsat af Dansk Selskab for Klinisk Mikrobiologi, Dansk Selskab for Infektionsmedicin og Dansk Neurologisk Selskab.
Rare case of septic shock combined with meningitis caused by Pasteurella multocida without a history of cat and dog bites
BMC Infectious Diseases, 17.03.2024
Tilføjet 17.03.2024
Abstract Background Pasteurella multocida is a zoonotic pathogen that mainly causes local skin and soft tissue infections in the human body through cat and dog bites. It rarely causes bacteraemia (or sepsis) and meningitis. We reported a case of septic shock and meningitis caused by P. multocida in a patient without a history of cat and dog bites. Case presentation An 84-year-old male patient was urgently sent to the emergency department after he was found with unclear consciousness for 8 h, accompanied by limb tremors and urinary incontinence. In the subsequent examination, P. multocida was detected in the blood culture and wound secretion samples of the patient. However, it was not detected in the cerebrospinal fluid culture, but its DNA sequence was detected. Therefore, the patient was clearly diagnosed with septic shock and meningitis caused by P. multocida. The patient had no history of cat or dog contact or bite. The patient was subsequently treated with a combination of penicillin G, doxycycline, and ceftriaxone, and he was discharged after 35 days of hospitalisation. Conclusion This report presented a rare case of septic shock and meningitis caused by P. multocida, which was not related to a cat or dog bite. Clinical doctors should consider P. multocida as a possible cause of sepsis or meningitis and should be aware of its potential seriousness even in the absence of animal bites.
[Articles] Development and validation of quantitative PCR assays for HIV-associated cryptococcal meningitis in sub-Saharan Africa: a diagnostic accuracy study
Tshepiso Mbangiwa, Aude Sturny-Leclère, Kwana Lechiile, Cheusisime Kajanga, Timothée Boyer-Chammard, Jennifer C Hoving, Tshepo Leeme, Melanie Moyo, Nabila Youssouf, David S Lawrence, Henry Mwandumba, Mosepele Mosepele, Thomas S Harrison, Joseph N Jarvis, Olivier Lortholary, Alexandre Alanio, AMBITION Study Group
The Lancet Microbe, 6.03.2024
Tilføjet 6.03.2024
QSP1 and 28S rRNA assays are useful in identifying Cryptococcus species. qPCR results correlate well with baseline quantitative cryptococcal culture and show a similar decline in fungal load during induction therapy. These assays could be a faster alternative to quantitative cryptococcal culture to determine fungal load clearance. The clinical implications of the possible detection of viable but non-culturable cells in CSF during induction therapy remain unclear.
How common is otogenic meningitis? A retrospective study in southern Sweden over 18 years
Infection, 5.03.2024
Tilføjet 5.03.2024
Abstract Background Bacterial meningitis is a rare, but life-threatening disease, which sometimes occurs as a complication to acute otitis media (AOM). The proportion of meningitis cases originating from AOM is not clear. Purpose The aim of this study was to investigate the proportion of meningitis cases caused by AOM, to compare risk factors, bacteriology and outcome between otogenic and non-otogenic meningitis, and to analyse the incidence of bacterial meningitis after the introduction of conjugate pneumococcal vaccines (PCV). Methods The medical charts of all patients admitted to hospitals in southern Sweden with bacterial meningitis between 2000 and 2017 were retrieved. Based on otoscopy and/or imaging, the proportion of otogenic meningitis cases was calculated, as were annual incidences. Results A total of 216 patients were identified, 25 of whom died. The proportion of otogenic meningitis was 31% but varied from 6% among teenagers to 40% among adults. Before PCV, 23% of all meningitis cases were children
How common is otogenic meningitis? A retrospective study in southern Sweden over 18 years
Infection, 29.02.2024
Tilføjet 29.02.2024
Abstract Background Bacterial meningitis is a rare, but life-threatening disease, which sometimes occurs as a complication to acute otitis media (AOM). The proportion of meningitis cases originating from AOM is not clear. Purpose The aim of this study was to investigate the proportion of meningitis cases caused by AOM, to compare risk factors, bacteriology and outcome between otogenic and non-otogenic meningitis, and to analyse the incidence of bacterial meningitis after the introduction of conjugate pneumococcal vaccines (PCV). Methods The medical charts of all patients admitted to hospitals in southern Sweden with bacterial meningitis between 2000 and 2017 were retrieved. Based on otoscopy and/or imaging, the proportion of otogenic meningitis cases was calculated, as were annual incidences. Results A total of 216 patients were identified, 25 of whom died. The proportion of otogenic meningitis was 31% but varied from 6% among teenagers to 40% among adults. Before PCV, 23% of all meningitis cases were children
How common is otogenic meningitis? A retrospective study in southern Sweden over 18 years
Infection, 29.02.2024
Tilføjet 29.02.2024
Abstract Background Bacterial meningitis is a rare, but life-threatening disease, which sometimes occurs as a complication to acute otitis media (AOM). The proportion of meningitis cases originating from AOM is not clear. Purpose The aim of this study was to investigate the proportion of meningitis cases caused by AOM, to compare risk factors, bacteriology and outcome between otogenic and non-otogenic meningitis, and to analyse the incidence of bacterial meningitis after the introduction of conjugate pneumococcal vaccines (PCV). Methods The medical charts of all patients admitted to hospitals in southern Sweden with bacterial meningitis between 2000 and 2017 were retrieved. Based on otoscopy and/or imaging, the proportion of otogenic meningitis cases was calculated, as were annual incidences. Results A total of 216 patients were identified, 25 of whom died. The proportion of otogenic meningitis was 31% but varied from 6% among teenagers to 40% among adults. Before PCV, 23% of all meningitis cases were children
Cerebrospinal fluid inflammatory markers to differentiate between neonatal bacterial meningitis and sepsis: a prospective study of diagnostic accuracy
Nina S. Groeneveld, Sabine E. Olie, Douwe H. Visser, Linde Snoek, Diederik van de Beek, Matthijs C. Brouwer, Merijn W. Bijlsma, NOGBS study group
International Journal of Infectious Diseases, 21.02.2024
Tilføjet 21.02.2024
Neonatal and infant meningitis and sepsis are associated with substantial mortality and long-term morbidity.[1] Early detection of meningitis in suspected sepsis patients is important because of the difference in empiric antibiotic regimen, dosage and duration of antibiotic treatment. Also, it influences the need for monitoring of complications during hospitalization, as well as the risk of long-term neurodevelopmental impairment.[2] The interpretation of CSF parameters in neonates can be difficult due to considerable overlap of CSF characteristics between sepsis and meningitis.
Evaluation of enterovirus concentration, species identification, and cerebrospinal fluid parameters in patients of different ages with aseptic meningitis in São Paulo, Brazil
Layla Honorato, Noely Evangelista Ferreira, Renan Barros Domingues, Carlos Senne, Fernando Brunale Vilela de Moura Leite, Márcio Vega dos Santos, Gustavo Bruniera Peres Fernandes, Heuder Gustavo Oliveira Paião, Lucy Santos Vilas Boas, Antonio Charlys da Costa, Tânia Regina Tozetto‐Mendoza, Steven S. Witkin, Maria Cássia Mendes‐Correa
Journal of Medical Virology, 15.02.2024
Tilføjet 15.02.2024
Journal of Medical Virology, Volume 96, Issue 2, February 2024.
Tracking cryptococcal meningitis to monitor HIV program success during the Treat-All era: An analysis of national data in Botswana
Clinical Infectious Diseases, 10.02.2024
Tilføjet 10.02.2024
Abstract Background Cryptococcal meningitis causes substantial mortality in high-HIV prevalence African countries despite advances in disease management and increasing antiretroviral therapy coverage. Reliable diagnosis of cryptococcal meningitis is cheap and more accessible than other indicators of AHD burden such as CD4 testing or investigation for disseminated tuberculosis; therefore, monitoring cryptococcal meningitis incidence has the potential to serve as a valuable metric of HIV programmatic success.Methods Botswana national meningitis surveillance data from 2015 to 2022 were obtained from electronic health records. All electronic laboratory records from cerebrospinal fluid samples analysed within government healthcare facilities in Botswana were extracted from a central online repository. Adjustments for missing data were made through triangulation with prospective cohort study datasets. Cryptococcal meningitis case frequency was enumerated using a case definition and incidence calculated using national census data.Results A total of 1,744 episodes of cryptococcal meningitis were identified; incidence declined from 15.0 (95% CI 13.4-16.7) cases/100,000 person-years in 2015 to 7.4 (95% CI 6.4-8.6) cases/100,000 person-years in 2022. However, the rate of decline slowed following the introduction of universal treatment in 2016. The highest incidence was observed in men and individuals aged 40-44. The proportion of cases diagnosed through cryptococcal antigen testing increased from 35.5% to 86.3%.Conclusion Cryptococcal meningitis incidence has decreased in Botswana following expansion of ART coverage but persists at a stubbornly high incidence. Most cases are now diagnosed through the cheap and easy-to-use cryptococcal antigen test highlighting the potential of using cryptococcal meningitis as key metric of programme success in the Treat All era.
Correction: High burden of cryptococcal antigenemia and meningitis among patients presenting at an emergency department in Maputo, Mozambique
Robert Deiss, Carolina V. Loreti, Ana G. Gutierrez, Eudoxia Filipe, Milton Tatia, Sheila Issufo, Iza Ciglenecki, Anne Loarec, Henriques Vivaldo, Carmen Barra, Carolina Siufi, Lucas Molfino, Natalia Tamayo Antabak
PLoS One Infectious Diseases, 9.02.2024
Tilføjet 9.02.2024
by Robert Deiss, Carolina V. Loreti, Ana G. Gutierrez, Eudoxia Filipe, Milton Tatia, Sheila Issufo, Iza Ciglenecki, Anne Loarec, Henriques Vivaldo, Carmen Barra, Carolina Siufi, Lucas Molfino, Natalia Tamayo Antabak
Neurovascular Complications of Iatrogenic Fusarium solani Meningitis
Nora Strong, Grant Meeks, Sunil A. Sheth, Louise McCullough, Julian A. Villalba, Chunfeng Tan, Andrew Barreto, Audrey Wanger, Michelle McDonald, Peter Kan, Hashem Shaltoni, Jose Campo Maldonado, Victoria Parada, Ameer E. Hassan, Sarah Reagan-Steiner, Tom Chiller, Jeremy A.W. Gold, Dallas J. Smith, Luis Ostrosky-Zeichner
New England Journal of Medicine, 8.02.2024
Tilføjet 8.02.2024
New England Journal of Medicine, Volume 390, Issue 6, Page 522-529, February 2024.
A novel diagnostic model for tuberculous meningitis using Bayesian latent class analysis
BMC Infectious Diseases, 7.02.2024
Tilføjet 7.02.2024
Abstract Background Diagnosis of tuberculous meningitis (TBM) is hampered by the lack of a gold standard. Current microbiological tests lack sensitivity and clinical diagnostic approaches are subjective. We therefore built a diagnostic model that can be used before microbiological test results are known. Methods We included 659 individuals aged (ge 16) years with suspected brain infections from a prospective observational study conducted in Vietnam. We fitted a logistic regression diagnostic model for TBM status, with unknown values estimated via a latent class model on three mycobacterial tests: Ziehl–Neelsen smear, Mycobacterial culture, and GeneXpert. We additionally re-evaluated mycobacterial test performance, estimated individual mycobacillary burden, and quantified the reduction in TBM risk after confirmatory tests were negative. We also fitted a simplified model and developed a scoring table for early screening. All models were compared and validated internally. Results Participants with HIV, miliary TB, long symptom duration, and high cerebrospinal fluid (CSF) lymphocyte count were more likely to have TBM. HIV and higher CSF protein were associated with higher mycobacillary burden. In the simplified model, HIV infection, clinical symptoms with long duration, and clinical or radiological evidence of extra-neural TB were associated with TBM At the cutpoints based on Youden’s Index, the sensitivity and specificity in diagnosing TBM for our full and simplified models were 86.0% and 79.0%, and 88.0% and 75.0% respectively. Conclusion Our diagnostic model shows reliable performance and can be developed as a decision assistant for clinicians to detect patients at high risk of TBM. Summary Diagnosis of tuberculous meningitis is hampered by the lack of gold standard. We developed a diagnostic model using latent class analysis, combining confirmatory test results and risk factors. Models were accurate, well-calibrated, and can support both clinical practice and research.
Anti-GM-CSF autoantibodies predict outcome of cryptococcal meningitis in patients not infected with HIV: a cohort study
Ying-Kui Jiang, Ling-Hong Zhou, Jia-Hui Cheng, Jun-Hao Zhu, Yu Luo, Li Li, Min Zhu, Rong-Sheng Zhu, Wen-Jia Qiu, Hua-Zhen Zhao, Xuan Wang, Jun-Tian Huang, Oliver A. Cornely, Wen-Hong Zhang, Li-Ping Zhu
Clinical Microbiology and Infection, 29.01.2024
Tilføjet 29.01.2024
To explore the seroprevalence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies in non-HIV cryptococcal meningitis (CM) and assess its predictive value for survival.
The ability of a 3-gene host signature in blood to distinguish tuberculous meningitis from other brain infections
Journal of Infectious Diseases, 4.01.2024
Tilføjet 4.01.2024
Abstract Background Tuberculous meningitis (TBM) is difficult to diagnose. We investigated whether a 3-gene host response signature in blood can distinguish TBM from other brain infections.Methods The expression of 3 genes (Dual specificity phosphatase 3- DUSP3, Guanylate-binding protein- GBP5, Krupple-like factor 2- KLF2) was analysed by RNA sequencing of archived whole blood from four cohorts of Vietnamese adults: 281 with TBM; 279 with pulmonary tuberculosis; 50 with other brain infections; and 30 healthy controls. ‘TB scores’ (combined 3-gene expression) were calculated following published methodology and discriminatory performance compared using area under a receiver operator characteristic curve (AUC).Results GBP5 was upregulated in TBM compared to other brain infections (p
Recurrent bacterial meningitis in children in the Netherlands: a nationwide surveillance study
Snoek, L., van Kassel, M. N., Koelman, D. L. H., van der Ende, A., van Sorge, N. M., Brouwer, M. C., van de Beek, D., Bijlsma, M. W.
BMJ Open, 30.12.2023
Tilføjet 30.12.2023
ObjectivesThis study aimed to estimate the recurrence rate of culture-positive bacterial meningitis in children in the Netherlands. DesignNationwide surveillance study, using the database of the Netherlands Reference Laboratory for Bacterial Meningitis to identify patients with culture-positive bacterial meningitis during childhood. SettingThe study was based in the Netherlands. ParticipantsA total of 9731 children with a first bacterial meningitis episode between 1 July 1987 and 30 June 2019 were identified. Primary and secondary outcome measuresRecurrence was defined as a subsequent episode >28 days, or caused by a different pathogen. Annual incidence and incidence rate ratios (IRRs) comparing the periods 1988–2003 and 2004–2019 were calculated. Predictors of recurrent meningitis were assessed using Cox proportional hazards regression. ResultsSixty-three (0.6%) of the 9731 children with a first bacterial meningitis episode contracted recurrent meningitis. Neisseria meningitidis was the leading pathogen for first meningitis episodes (52%) and Streptococcus pneumoniae for recurrent episodes (52%). The median annual incidence of first episodes per 100 000 children decreased from 11.81 (IQR 11.26–17.60) in 1988–2003 to 2.60 (IQR 2.37–4.07) in 2004–2019 (IRR 0.25, 95% CI 0.23 to 0.26). The incidence of recurrences did not change: 0.06 (IQR 0.02–0.11) in 1988–2003 to 0.03 (IQR 0.00–0.06) in 2004–2019 (IRR 0.65, 95% CI 0.39 to 1.1). Age above 5 years (OR 3.6 (95% CI 1.5 to 8.3)) and a first episode due to Escherichia coli (OR 25.7 (95% CI 7.2 to 92.0)) were associated with higher risks of recurrence. ConclusionThe recurrence rate of childhood bacterial meningitis in the Netherlands was 0.6%. While the incidence rate of first episodes decreased substantially, this was not the case for recurrent episodes. Older age and a first episode due to E. coli were associated with higher recurrence risks.
Development and validation of a new model for the early diagnosis of tuberculous meningitis in adults based on simple clinical and laboratory parameters
BMC Infectious Diseases, 28.12.2023
Tilføjet 28.12.2023
Abstract Background The differential diagnosis between tuberculous meningitis (TBM) and viral meningitis (VM) or bacterial meningitis (BM) remains challenging in clinical practice, particularly in resource-limited settings. This study aimed to establish a diagnostic model that can accurately and early distinguish TBM from both VM and BM in adults based on simple clinical and laboratory parameters. Methods Patients diagnosed with TBM or non-TBM (VM or BM) between January 2012 and October 2021 were retrospectively enrolled from the General Hospital (derivation cohort) and Branch Hospital (validation cohort) of Ningxia Medical University. Demographic characteristics, clinical symptoms, concomitant diseases, and cerebrospinal fluid (CSF) parameters were collated. Univariable logistic analysis was performed in the derivation cohort to identify significant variables (P 5 days, weight loss > 5% of the original weight within 6 months, CSF lymphocyte ratio > 50%, CSF glucose concentration
Development and validation of a new model for the early diagnosis of tuberculous meningitis in adults based on simple clinical and laboratory parameters
BMC Infectious Diseases, 22.12.2023
Tilføjet 22.12.2023
Abstract Background The differential diagnosis between tuberculous meningitis (TBM) and viral meningitis (VM) or bacterial meningitis (BM) remains challenging in clinical practice, particularly in resource-limited settings. This study aimed to establish a diagnostic model that can accurately and early distinguish TBM from both VM and BM in adults based on simple clinical and laboratory parameters. Methods Patients diagnosed with TBM or non-TBM (VM or BM) between January 2012 and October 2021 were retrospectively enrolled from the General Hospital (derivation cohort) and Branch Hospital (validation cohort) of Ningxia Medical University. Demographic characteristics, clinical symptoms, concomitant diseases, and cerebrospinal fluid (CSF) parameters were collated. Univariable logistic analysis was performed in the derivation cohort to identify significant variables (P 5 days, weight loss > 5% of the original weight within 6 months, CSF lymphocyte ratio > 50%, CSF glucose concentration
Long term survival, health, social functioning, and education in patients with European Lyme neuroborreliosis: nationwide population based cohort study.
To estimate long term survival, health, and educational/social functioning in patients with Lyme neuroborreliosis compared with the general population.
Viral meningitis: current issues in diagnosis and treatment.
Curr Opin Infect Dis 2017; 30(2):248-256
McGill F, Griffiths MJ, Solomon T
The purpose of this review is to give an overview of viral meningitis and then focus in on some of the areas of uncertainty in diagnostics, treatment and outcome.
ESCMID guideline: diagnosis and treatment of acute bacterial meningitis.
Clin Microbiol Infect 2016; 22 Suppl 3:S37-62
van de Beek D, Cabellos C, Dzupova O, Esposito S, Klein M, Kloek AT, Leib SL, Mourvillier B, Ostergaard C, Pagliano P, Pfister HW, Read RC, Sipahi OR, Brouwer MC
PMID: 27062097
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Randomized Trial of Longer-Term Therapy for Symptoms Attributed to Lyme Disease.
N Engl J Med 2016; 374(13):1209-20
Berende A, ter Hofstede HJ, Vos FJ, van Middendorp H, Vogelaar ML, Tromp M, van den Hoogen FH, Donders AR, Evers AW, Kullberg BJ
The treatment of persistent symptoms attributed to Lyme disease remains controversial. We assessed whether longer-term antibiotic treatment of persistent symptoms attributed to Lyme disease leads to better outcomes than does shorter-term treatment.
Herpes simplex and varicella zoster CNS infections: clinical presentations, treatments and outcomes.
Infection 2016; 44(3):337-45
Kaewpoowat Q, Salazar L, Aguilera E, Wootton SH, Hasbun R
To describe the clinical manifestations, cerebrospinal fluid (CSF) characteristics, imaging studies and prognostic factors of adverse clinical outcomes (ACO) among adults with herpes simplex virus (HSV) or varicella zoster virus (VZV) CNS infections.
Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium.
Clin Infect Dis 2013; 57(8):1114-28
Venkatesan A, Tunkel AR, Bloch KC, Lauring AS, Sejvar J, Bitnun A, Stahl JP, Mailles A, Drebot M, Rupprecht CE, Yoder J, Cope JR, Wilson MR, Whitley RJ, Sullivan J, Granerod J, Jones C, Eastwood K, Ward KN, Durrheim DN, Solbrig MV, Guo-Dong L, Glaser CA
Encephalitis continues to result in substantial morbidity and mortality worldwide. Advances in diagnosis and management have been limited, in part, by a lack of consensus on case definitions, standardized diagnostic approaches, and priorities for research.
Lyme borreliosis (Lyme disease) is caused by spirochaetes of the Borrelia burgdorferi sensu lato species complex, which are transmitted by ticks. The most common clinical manifestation is erythema migrans, which eventually resolves, even without antibiotic treatment. However, the infecting pathogen can spread to other tissues and organs, causing more severe manifestations that can involve a patient's skin, nervous system, joints, or heart. The incidence of this disease is increasing in many countries. Laboratory evidence of infection, mainly serology, is essential for diagnosis, except in the case of typical erythema migrans. Diagnosed cases are usually treated with antibiotics for 2-4 weeks and most patients make an uneventful recovery. No convincing evidence exists to support the use of antibiotics for longer than 4 weeks, or for the persistence of spirochaetes in adequately treated patients. Prevention is mainly accomplished by protecting against tick bites. There is no vaccine available for human beings.
Lyme borreliosis, caused by spirochaetes of the Borrelia burgdorferi genospecies complex, is the most commonly reported tick-borne infection in Europe and North America. The non-specific nature of many of its clinical manifestations presents a diagnostic challenge and concise case definitions are essential for its satisfactory management. Lyme borreliosis is very similar in Europe and North America but the greater variety of genospecies in Europe leads to some important differences in clinical presentation. These new case definitions for European Lyme borreliosis emphasise recognition of clinical manifestations supported by relevant laboratory criteria and may be used in a clinical setting and also for epidemiological investigations.
Dexamethasone in adults with bacterial meningitis.
N Engl J Med 2002; 347(20):1549-56
de Gans J, van de Beek D
Mortality and morbidity rates are high among adults with acute bacterial meningitis, especially those with pneumococcal meningitis. In studies of bacterial meningitis in animals, adjuvant treatment with corticosteroids has beneficial effects.
An epidemiologic study of Lyme disease in southern Sweden.
N Engl J Med 1995; 333(20):1319-27
Berglund J, Eitrem R, Ornstein K, Lindberg A, Ringér A, Elmrud H, Carlsson M, Runehagen A, Svanborg C, Norrby R
Lyme disease is the most common vector-borne infection in some temperate regions of the Northern Hemisphere. However, for most areas of endemic disease reliable epidemiologic data are sparse.