CXCL13 in patients with facial palsy caused by varicella zoster virus and Borrelia burgdorferi: a comparative study

High cerebrospinal fluid (CSF) concentrations of the chemokine CXCL13 have been associated with Lyme neuroborreliosis (LNB), and have recently been studied as a potential diagnostic marker. It has proven difficult to establish a reliable diagnostic cut-off, possibly in part due to heterogenicity of case–control groups. Our purpose was to investigate CSF CXCL13 concentrations in patients with similar clinical presentations, facial palsy. We retrospectively included patients with facial palsy associated with LNB (n = 21), or varicella zoster virus (VZV) (n = 26). Median CXCL13 concentrations were significantly higher in patients with LNB facial palsy compared to VZV facial palsy. Receiver-operating characteristic analyses yielded an optimal cut-off concentration at 34.5 pg/mL (sensitivity 85.7%, specificity of 84.6%), lower than that in previous studies. Although the analysis has potential, it is still not adequately established that CXCL13 provides additional, clinically useful, diagnostic information over current recommendations

Regional risks and seasonality in travel-associated campylobacteriosis

BACKGOUND: The epidemiology of travel-associated campylobacteriosis is still largely unclear, and various known risk factors could only explain limited proportions of the recorded cases. METHODS: Using data from 28,704 notifications of travel-associated campylobacteriosis in Sweden 1997 to 2003 and travel patterns of 16,255 Swedish residents with overnight travel abroad in the same years, we analysed risks for travel-associated campylobacteriosis in 19 regions of the world, and looked into the seasonality of the disease in each of these regions. RESULTS: The highest risk was seen in returning travellers from the Indian subcontinent (1,253/100,000 travellers), and the lowest in travellers from the other Nordic countries (3/100,000 travellers). In Africa, large differences in risk between regions were noted, with 502 /100,000 in travellers from East Africa, compared to 76/100,00 from West Africa and 50/100,000 from Central Africa. A distinct seasonal pattern was seen in all temperate regions with peaks in the summer, while no or less distinct seasonality was seen in tropical regions. In travellers to the tropics, the highest risk was seen in children below the age of six. CONCLUSIONS: Data on infections in returning travellers together with good denominator data could provide comparable data on travel risks in various regions of the world

Neuroinflammation in Lyme neuroborreliosis affects amyloid metabolism

<p>Abstract</p> <p>Background</p> <p>The metabolism of amyloid precursor protein (APP) and β-amyloid (Aβ) is widely studied in Alzheimer's disease, where Aβ deposition and plaque development are essential components of the pathogenesis. However, the physiological role of amyloid in the adult nervous system remains largely unknown. We have previously found altered cerebral amyloid metabolism in other neuroinflammatory conditions. To further elucidate this, we investigated amyloid metabolism in patients with Lyme neuroborreliosis (LNB).</p> <p>Methods</p> <p>The first part of the study was a cross-sectional cohort study in 61 patients with acute facial palsy (19 with LNB and 42 with idiopathic facial paresis, Bell's palsy) and 22 healthy controls. CSF was analysed for the β-amyloid peptides Aβ38, Aβ40 and Aβ42, and the amyloid precursor protein (APP) isoforms α-sAPP and β-sAPP. CSF total-tau (T-tau), phosphorylated tau (P-tau) and neurofilament protein (NFL) were measured to monitor neural cell damage. The second part of the study was a prospective cohort-study in 26 LNB patients undergoing consecutive lumbar punctures before and after antibiotic treatment to study time-dependent dynamics of the biomarkers.</p> <p>Results</p> <p>In the cross-sectional study, LNB patients had lower levels of CSF α-sAPP, β-sAPP and P-tau, and higher levels of CSF NFL than healthy controls and patients with Bell's palsy. In the prospective study, LNB patients had low levels of CSF α-sAPP, β-sAPP and P-tau at baseline, which all increased towards normal at follow-up.</p> <p>Conclusions</p> <p>Amyloid metabolism is altered in LNB. CSF levels of α-sAPP, β-sAPP and P-tau are decreased in acute infection and increase after treatment. In combination with earlier findings in multiple sclerosis, cerebral SLE and HIV with cerebral engagement, this points to an influence of neuroinflammation on amyloid metabolism.</p

Potential risk factors associated with human encephalitis: application of canonical correlation analysis

<p>Abstract</p> <p>Background</p> <p>Infection of the CNS is considered to be the major cause of encephalitis and more than 100 different pathogens have been recognized as causative agents. Despite being identified worldwide as an important public health concern, studies on encephalitis are very few and often focus on particular types (with respect to causative agents) of encephalitis (e.g. West Nile, Japanese, etc.). Moreover, a number of other infectious and non-infectious conditions present with similar symptoms, and distinguishing encephalitis from other disguising conditions continues to a challenging task.</p> <p>Methods</p> <p>We used canonical correlation analysis (CCA) to assess associations between set of exposure variable and set of symptom and diagnostic variables in human encephalitis. Data consists of 208 confirmed cases of encephalitis from a prospective multicenter study conducted in the United Kingdom. We used a covariance matrix based on Gini's measure of similarity and used permutation based approaches to test significance of canonical variates.</p> <p>Results</p> <p>Results show that weak pair-wise correlation exists between the risk factor (exposure and demographic) and symptom/laboratory variables. However, the first canonical variate from CCA revealed strong multivariate correlation (ρ = 0.71, se = 0.03, p = 0.013) between the two sets. We found a moderate correlation (ρ = 0.54, se = 0.02) between the variables in the second canonical variate, however, the value is not statistically significant (p = 0.68). Our results also show that a very small amount of the variation in the symptom sets is explained by the exposure variables. This indicates that host factors, rather than environmental factors might be important towards understanding the etiology of encephalitis and facilitate early diagnosis and treatment of encephalitis patients.</p> <p>Conclusions</p> <p>There is no standard laboratory diagnostic strategy for investigation of encephalitis and even experienced physicians are often uncertain about the cause, appropriate therapy and prognosis of encephalitis. Exploration of human encephalitis data using advanced multivariate statistical modelling approaches that can capture the inherent complexity in the data is, therefore, crucial in understanding the causes of human encephalitis. Moreover, application of multivariate exploratory techniques will generate clinically important hypotheses and offer useful insight into the number and nature of variables worthy of further consideration in a confirmatory statistical analysis.</p

The metagenomic approach and causality in virology

Nowadays, the metagenomic approach has been a very important tool in the discovery of new viruses in environmental and biological samples. Here we discuss how these discoveries may help to elucidate the etiology of diseases and the criteria necessary to establish a causal association between a virus and a disease

Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis

Herpes simplex encephalitis (HSE) is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats) with the asymptomatic infection of BN (Brown Norway). Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains), displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus) named Hse6 towards the end of chromosome 4 (160.89-174Mb) containing the Vwf (von Willebrand factor) gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism). Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008) after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE

Free-Living Turtles Are a Reservoir for Salmonella but Not for Campylobacter

Different studies have reported the prevalence of Salmonella in turtles and its role in reptile-associated salmonellosis in humans, but there is a lack of scientific literature related with the epidemiology of Campylobacter in turtles. The aim of this study was to evaluate the prevalence of Campylobacter and Salmonella in free-living native (Emys orbicularis, n=83) and exotic (Trachemys scripta elegans, n=117) turtles from 11 natural ponds in Eastern Spain. In addition, different types of samples (cloacal swabs, intestinal content and water from Turtle containers) were compared. Regardless of the turtle species, natural ponds where individuals were captured and the type of sample taken, Campylobacter was not detected. Salmonella was isolated in similar proportions in native (8.0±3.1%) and exotic (15.0±3.3%) turtles (p=0.189). The prevalence of Salmonella positive turtles was associated with the natural ponds where animals were captured. Captured turtles from 8 of the 11 natural ponds were positive, ranged between 3.0±3.1% and 60.0±11.0%. Serotyping revealed 8 different serovars among four Salmonella enterica subspecies: S. enterica subsp. enterica (n = 21), S. enterica subsp. salamae (n = 2), S. enterica subsp. diarizonae (n = 3), and S. enterica subsp. houtenae (n = 1). Two serovars were predominant: S. Thompson (n=16) and S. typhimurium (n=3). In addition, there was an effect of sample type on Salmonella detection. The highest isolation of Salmonella was obtained from intestinal content samples (12.0±3.0%), while lower percentages were found for water from the containers and cloacal swabs (8.0±2.5% and 3.0±1.5%, respectively). Our results imply that free-living turtles are a risk factor for Salmonella transmission, but do not seem to be a reservoir for Campylobacter. We therefore rule out turtles as a risk factor for human campylobacteriosis. Nevertheless, further studies should be undertaken in other countries to confirm these results.This work was supported by the Conselleria de Infraestructura, Territorio y Medio Ambiente for their assistance and financial support (Life09-Trachemys, Resolution 28/02/12 CITMA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Marín, C.; Ingresa-Capaccioni, S.; González Bodí, S.; Marco Jiménez, F.; Vega Garcia, S. (2013). Free-Living Turtles Are a Reservoir for Salmonella but Not for Campylobacter. PLoS ONE. 8(8):1-6. https://doi.org/10.1371/journal.pone.0072350S1688(2012). The European Union Summary Report on Trends and Sources of Zoonoses, Zoonotic Agents and Food‐borne Outbreaks in 2010. EFSA Journal, 10(3). doi:10.2903/j.efsa.2012.2597Kapperud, G. (2003). Factors Associated with Increased and Decreased Risk of Campylobacter Infection: A Prospective Case-Control Study in Norway. American Journal of Epidemiology, 158(3), 234-242. doi:10.1093/aje/kwg139Mermin, J., Hutwagner, L., Vugia, D., Shallow, S., Daily, P., … Bender, J. (2004). Reptiles, Amphibians, and HumanSalmonellaInfection: A Population‐Based, Case‐Control Study. Clinical Infectious Diseases, 38(s3), S253-S261. doi:10.1086/381594De Jong, B., Andersson, Y., & Ekdahl, K. (2005). Effect of Regulation and Education on Reptile-associated Salmonellosis. Emerging Infectious Diseases, 11(3), 398-403. doi:10.3201/eid1103.040694NAKADAI, A., KUROKI, T., KATO, Y., SUZUKI, R., YAMAI, S., YAGINUMA, C., … HAYASHIDANI, H. (2005). Prevalence of Salmonella spp. in Pet Reptiles in Japan. Journal of Veterinary Medical Science, 67(1), 97-101. doi:10.1292/jvms.67.97Lafuente, S., Bellido, J. B., Moraga, F. A., Herrera, S., Yagüe, A., Montalvo, T., … Caylà, J. A. (2013). Salmonella paratyphi B and Salmonella litchfield outbreaks associated with pet turtle exposure in Spain. Enfermedades Infecciosas y Microbiología Clínica, 31(1), 32-35. doi:10.1016/j.eimc.2012.05.013Van PELT, W., de WIT, M. A. S., WANNET, W. J. B., LIGTVOET, E. J. J., WIDDOWSON, M. A., & van DUYNHOVEN, Y. T. H. P. (2003). Laboratory surveillance of bacterial gastroenteric pathogens in The Netherlands, 1991–2001. Epidemiology and Infection, 130(3), 431-441. doi:10.1017/s0950268803008392Havelaar, A. H., Haagsma, J. A., Mangen, M.-J. J., Kemmeren, J. M., Verhoef, L. P. B., Vijgen, S. M. C., … van Pelt, W. (2012). Disease burden of foodborne pathogens in the Netherlands, 2009. International Journal of Food Microbiology, 156(3), 231-238. doi:10.1016/j.ijfoodmicro.2012.03.029DOORDUYN, Y., VAN PELT, W., SIEZEN, C. L. E., VAN DER HORST, F., VAN DUYNHOVEN, Y. T. H. P., HOEBEE, B., & JANSSEN, R. (2007). Novel insight in the association between salmonellosis or campylobacteriosis and chronic illness, and the role of host genetics in susceptibility to these diseases. Epidemiology and Infection, 136(9), 1225-1234. doi:10.1017/s095026880700996xHAAGSMA, J. A., SIERSEMA, P. D., DE WIT, N. J., & HAVELAAR, A. H. (2010). Disease burden of post-infectious irritable bowel syndrome in The Netherlands. Epidemiology and Infection, 138(11), 1650-1656. doi:10.1017/s0950268810000531Allos, B. M., & Blaser, M. J. (1995). Campylobacter jejuni and the Expanding Spectrum of Related Infections. Clinical Infectious Diseases, 20(5), 1092-1101. doi:10.1093/clinids/20.5.1092Friedman, C. R., Hoekstra, R. M., Samuel, M., Marcus, R., Bender, J., … Shiferaw, B. (2004). Risk Factors for SporadicCampylobacterInfection in the United States: A Case‐Control Study in FoodNet Sites. Clinical Infectious Diseases, 38(s3), S285-S296. doi:10.1086/381598STUDAHL, A., & ANDERSSON, Y. (2000). Risk factors for indigenous campylobacter infection: a Swedish case-control study. Epidemiology and Infection, 125(2), 269-275. doi:10.1017/s0950268899004562NEIMANN, J., ENGBERG, J., MØLBAK, K., & WEGENER, H. C. (2003). A case–control study of risk factors for sporadic campylobacter infections in Denmark. Epidemiology and Infection, 130(3), 353-366. doi:10.1017/s0950268803008355DOORDUYN, Y., VAN DEN BRANDHOF, W. E., VAN DUYNHOVEN, Y. T. H. P., BREUKINK, B. J., WAGENAAR, J. A., & VAN PELT, W. (2010). Risk factors for indigenous Campylobacter jejuni and Campylobacter coli infections in The Netherlands: a case-control study. Epidemiology and Infection, 138(10), 1391-1404. doi:10.1017/s095026881000052xSchroter, M., Roggentin, P., Hofmann, J., Speicher, A., Laufs, R., & Mack, D. (2004). Pet Snakes as a Reservoir for Salmonella enterica subsp. diarizonae (Serogroup IIIb): a Prospective Study. Applied and Environmental Microbiology, 70(1), 613-615. doi:10.1128/aem.70.1.613-615.2004Van Meervenne, E., Botteldoorn, N., Lokietek, S., Vatlet, M., Cupa, A., Naranjo, M., … Bertrand, S. (2009). Turtle-associated Salmonella septicaemia and meningitis in a 2-month-old baby. Journal of Medical Microbiology, 58(10), 1379-1381. doi:10.1099/jmm.0.012146-0Williams, L. P. (1965). Pet Turtles as a Cause of Human Salmonellosis. JAMA: The Journal of the American Medical Association, 192(5), 347. doi:10.1001/jama.1965.03080180005001Feeley, J. C., & Treger, M. D. (1969). Penetration of Turtle Eggs by Salmonella braenderup. Public Health Reports (1896-1970), 84(2), 156. doi:10.2307/4593527Mermin, J., Hoar, B., & Angulo, F. J. (1997). Iguanas and Salmonella Marina Infection in Children: A Reflection of the Increasing Incidence of Reptile-associated Salmonellosis in the United States. PEDIATRICS, 99(3), 399-402. doi:10.1542/peds.99.3.399Rodgers, G. L., Long, S. S., Smergel, E., & Dampier, C. (2002). Salmonella Infection Associated With a Pet Lizard in Siblings With Sickle Cell Anemia: An Avoidable Risk. Journal of Pediatric Hematology/Oncology, 24(1), 75-76. doi:10.1097/00043426-200201000-00020Tu, Z.-C., Zeitlin, G., Gagner, J.-P., Keo, T., Hanna, B. A., & Blaser, M. J. (2004). Campylobacter fetus of Reptile Origin as a Human Pathogen. Journal of Clinical Microbiology, 42(9), 4405-4407. doi:10.1128/jcm.42.9.4405-4407.2004Hidalgo-Vila, J., Díaz-Paniagua, C., Pérez-Santigosa, N., de Frutos-Escobar, C., & Herrero-Herrero, A. (2008). Salmonella in free-living exotic and native turtles and in pet exotic turtles from SW Spain. Research in Veterinary Science, 85(3), 449-452. doi:10.1016/j.rvsc.2008.01.011Harris, J. R., Neil, K. P., Behravesh, C. B., Sotir, M. J., & Angulo, F. J. (2010). Recent Multistate Outbreaks of HumanSalmonellaInfections Acquired from Turtles: A Continuing Public Health Challenge. Clinical Infectious Diseases, 50(4), 554-559. doi:10.1086/649932Geue, L., & Löschner, U. (2002). Salmonella enterica in reptiles of German and Austrian origin. Veterinary Microbiology, 84(1-2), 79-91. doi:10.1016/s0378-1135(01)00437-0Sánchez-Jiménez, M. M., Rincón-Ruiz, P. A., Duque, S., Giraldo, M. A., Ramírez-Monroy, D. M., Jaramillo, G., & Cardona-Castro, N. (2011). Salmonella enterica in semi-aquatic turtles in Colombia. The Journal of Infection in Developing Countries, 5(05), 361-364. doi:10.3855/jidc.1126HEALTH SURVEY OF WILD AND CAPTIVE BOG TURTLES (CLEMMYS MUHLENBERGII) IN NORTH CAROLINA AND VIRGINIA. (2002). Journal of Zoo and Wildlife Medicine, 33(4), 311-316. doi:10.1638/1042-7260(2002)033[0311:hsowac]2.0.co;2Richards, J. M., Brown, J. D., Kelly, T. R., Fountain, A. L., & Sleeman, J. M. (2004). ABSENCE OF DETECTABLE SALMONELLA CLOACAL SHEDDING IN FREE-LIVING REPTILES ON ADMISSION TO THE WILDLIFE CENTER OF VIRGINIA. Journal of Zoo and Wildlife Medicine, 35(4), 562-563. doi:10.1638/03-070Hidalgo-Vila, J., Díaz-Paniagua, C., de Frutos-Escobar, C., Jiménez-Martínez, C., & Pérez-Santigosa, N. (2007). Salmonella in free living terrestrial and aquatic turtles. Veterinary Microbiology, 119(2-4), 311-315. doi:10.1016/j.vetmic.2006.08.012Acheson, D., & Allos, B. M. (2001). Campylobacter jejuni Infections: Update on Emerging Issues and Trends. Clinical Infectious Diseases, 32(8), 1201-1206. doi:10.1086/319760Briones, V., Tellez, S., Goyache, J., Ballesteros, C., del Pilar Lanzarot, M., Dominguez, L., & Fernandez-Garayzabal, J. F. (2004). Salmonella diversity associated with wild reptiles and amphibians in Spain. Environmental Microbiology, 6(8), 868-871. doi:10.1111/j.1462-2920.2004.00631.xMan, S. M. (2011). The clinical importance of emerging Campylobacter species. Nature Reviews Gastroenterology & Hepatology, 8(12), 669-685. doi:10.1038/nrgastro.2011.191Ugarte-Ruiz, M., Gómez-Barrero, S., Porrero, M. C., Álvarez, J., García, M., Comerón, M. C., … Domínguez, L. (2012). Evaluation of four protocols for the detection and isolation of thermophilic Campylobacter from different matrices. Journal of Applied Microbiology, 113(1), 200-208. doi:10.1111/j.1365-2672.2012.05323.xJeffrey, J. S., Tonooka, K. H., & Lozanot, J. (2001). Prevalence of Campylobacter spp. from Skin, Crop, and Intestine of Commercial Broiler Chicken Carcasses at Processing. Poultry Science, 80(9), 1390-1392. doi:10.1093/ps/80.9.1390Perko-Mäkelä, P., Isohanni, P., Katzav, M., Lund, M., Hänninen, M.-L., & Lyhs, U. (2009). A longitudinal study of Campylobacter distribution in a turkey production chain. Acta Veterinaria Scandinavica, 51(1). doi:10.1186/1751-0147-51-18Saelinger, C. A., Lewbart, G. A., Christian, L. S., & Lemons, C. L. (2006). Prevalence ofSalmonellaspp in cloacal, fecal, and gastrointestinal mucosal samples from wild North American turtles. Journal of the American Veterinary Medical Association, 229(2), 266-268. doi:10.2460/javma.229.2.266Chambers, D. L., & Hulse, A. C. (2006). Salmonella Serovars in the Herpetofauna of Indiana County, Pennsylvania. Applied and Environmental Microbiology, 72(5), 3771-3773. doi:10.1128/aem.72.5.3771-3773.2006Gaertner, J. P., Hahn, D., Jackson, J., Forstner, M. R. J., & Rose, F. L. (2008). Detection of Salmonellae in Captive and Free-Ranging Turtles Using Enrichment Culture and Polymerase Chain Reaction. Journal of Herpetology, 42(2), 223-231. doi:10.1670/07-1731.1Magnino, S., Colin, P., Dei-Cas, E., Madsen, M., McLauchlin, J., Nöckler, K., … Van Peteghem, C. (2009). Biological risks associated with consumption of reptile products. International Journal of Food Microbiology, 134(3), 163-175. doi:10.1016/j.ijfoodmicro.2009.07.001XIA, X., ZHAO, S., SMITH, A., MCEVOY, J., MENG, J., & BHAGWAT, A. (2009). Characterization of Salmonella isolates from retail foods based on serotyping, pulse field gel electrophoresis, antibiotic resistance and other phenotypic properties. International Journal of Food Microbiology, 129(1), 93-98. doi:10.1016/j.ijfoodmicro.2008.11.007Franco, A., Hendriksen, R. S., Lorenzetti, S., Onorati, R., Gentile, G., Dell’Omo, G., … Battisti, A. (2011). Characterization of Salmonella Occurring at High Prevalence in a Population of the Land Iguana Conolophus subcristatus in Galápagos Islands, Ecuador. PLoS ONE, 6(8), e23147. doi:10.1371/journal.pone.0023147Scheelings, T. F., Lightfoot, D., & Holz, P. (2011). PREVALENCE OF SALMONELLA IN AUSTRALIAN REPTILES. Journal of Wildlife Diseases, 47(1), 1-11. doi:10.7589/0090-3558-47.1.1Pasmans, F., Blahak, S., Martel, A., & Pantchev, N. (2008). Introducing reptiles into a captive collection: The role of the veterinarian. The Veterinary Journal, 175(1), 53-68. doi:10.1016/j.tvjl.2006.12.009Strohl, P., Tilly, B., Fremy, S., Brisabois, A., & Guerin-Faublee, V. (2004). Prevalence of Salmonella shedding in faeces by captive chelonians. Veterinary Record, 154(2), 56-58. doi:10.1136/vr.154.2.5