International Network for Capacity Building for the Control of Emerging Viral Vector-Borne Zoonotic Diseases: Arbo-Zoonet

Arboviruses are arthropod-borne viruses, which include West Nile fever virus (WNFV), a mosquito-borne virus, Rift Valley fever virus (RVFV), a mosquito-borne virus, and Crimean-Congo haemorrhagic fever virus (CCHFV), a tick-borne virus. These arthropod-borne viruses can cause disease in different domestic and wild animals and in humans, posing a threat to public health because of their epidemic and zoonotic potential. In recent decades, the geographical distribution of these diseases has expanded. Outbreaks of WNF have already occurred in Europe, especially in the Mediterranean basin. Moreover, CCHF is endemic in many European countries and serious outbreaks have occurred, particularly in the Balkans, Turkey and Southern Federal Districts of Russia. In 2000, RVF was reported for the first time outside the African continent, with cases being confirmed in Saudi Arabia and Yemen. This spread was probably caused by ruminant trade and highlights that there is a threat of expansion of the virus into other parts of Asia and Europe. In the light of global warming and globalisation of trade and travel, public interest in emerging zoonotic diseases has increased. This is especially evident regarding the geographical spread of vector-borne diseases. A multi-disciplinary approach is now imperative, and groups need to collaborate in an integrated manner that includes vector control, vaccination programmes, improved therapy strategies, diagnostic tools and surveillance, public awareness, capacity building and improvement of infrastructure in endemic regions

Advances in our understanding of the pathogenesis of glomerular thrombotic microangiopathy

Glomerular thrombotic microangiopathy is a hallmark feature of haemolytic uraemic syndrome, the leading cause of acute renal failure in childhood. This paper is a review of the different mechanistic pathways that lead to this histological picture in the kidney. It will focus on atypical HUS and complement dysregulation, but will also highlight some other recent advances in our understanding of this condition, including the potential role of the molecule vascular endothelial growth factor- A (VEGF-A)

Inhibition of Interferon Induction and Action by the Nairovirus Nairobi Sheep Disease Virus/Ganjam Virus

The Nairoviruses are an important group of tick-borne viruses that includes pathogens of man (Crimean Congo hemorrhagic fever virus) and livestock animals (Dugbe virus, Nairobi sheep disease virus (NSDV)). NSDV is found in large parts of East Africa and the Indian subcontinent (where it is known as Ganjam virus). We have investigated the ability of NSDV to antagonise the induction and actions of interferon. Both pathogenic and apathogenic isolates could actively inhibit the induction of type 1 interferon, and also blocked the signalling pathways of both type 1 and type 2 interferons. Using transient expression of viral proteins or sections of viral proteins, these activities all mapped to the ovarian tumour-like protease domain (OTU) found in the viral RNA polymerase. Virus infection, or expression of this OTU domain in transfected cells, led to a great reduction in the incorporation of ubiquitin or ISG15 protein into host cell proteins. Point mutations in the OTU that inhibited the protease activity also prevented it from antagonising interferon induction and action. Interestingly, a mutation at a peripheral site, which had little apparent effect on the ability of the OTU to inhibit ubiquitination and ISG15ylation, removed the ability of the OTU to block the induction of type 1 and the action of type 2 interferons, but had a lesser effect on the ability to block type 1 interferon action, suggesting that targets other than ubiquitin and ISG15 may be involved in the actions of the viral OTU

Shiga Toxin 1 Induces on Lipopolysaccharide-Treated Astrocytes the Release of Tumor Necrosis Factor-alpha that Alter Brain-Like Endothelium Integrity

The hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia and renal dysfunction. The typical form of HUS is generally associated with infections by Gram-negative Shiga toxin (Stx)-producing Escherichia coli (STEC). Endothelial dysfunction induced by Stx is central, but bacterial lipopolysaccharide (LPS) and neutrophils (PMN) contribute to the pathophysiology. Although renal failure is characteristic of this syndrome, neurological complications occur in severe cases and is usually associated with death. Impaired blood-brain barrier (BBB) is associated with damage to cerebral endothelial cells (ECs) that comprise the BBB. Astrocytes (ASTs) are inflammatory cells in the brain and determine the BBB function. ASTs are in close proximity to ECs, hence the study of the effects of Stx1 and LPS on ASTs, and the influence of their response on ECs is essential. We have previously demonstrated that Stx1 and LPS induced activation of rat ASTs and the release of inflammatory factors such as TNF-α, nitric oxide and chemokines. Here, we demonstrate that rat ASTs-derived factors alter permeability of ECs with brain properties (HUVECd); suggesting that functional properties of BBB could also be affected. Additionally, these factors activate HUVECd and render them into a proagregant state promoting PMN and platelets adhesion. Moreover, these effects were dependent on ASTs secreted-TNF-α. Stx1 and LPS-induced ASTs response could influence brain ECs integrity and BBB function once Stx and factors associated to the STEC infection reach the brain parenchyma and therefore contribute to the development of the neuropathology observed in HUS

Age- and region-specific hepatitis B prevalence in Turkey estimated using generalized linear mixed models: a systematic review

Toy M, Önder FO, Wörmann T, et al. Age- and region-specific hepatitis B prevalence in Turkey estimated using generalized linear mixed models: a systematic review. BMC infectious diseases. 2011;11(1): 337.BACKGROUND: To provide a clear picture of the current hepatitis B situation, the authors performed a systematic review to estimate the age- and region-specific prevalence of chronic hepatitis B (CHB) in Turkey. METHODS: A total of 339 studies with original data on the prevalence of hepatitis B surface antigen (HBsAg) in Turkey and published between 1999 and 2009 were identified through a search of electronic databases, by reviewing citations, and by writing to authors. After a critical assessment, the authors included 129 studies, divided into categories: 'age-specific'; 'region-specific'; and 'specific population group'. To account for the differences among the studies, a generalized linear mixed model was used to estimate the overall prevalence across all age groups and regions. For specific population groups, the authors calculated the weighted mean prevalence. RESULTS: The estimated overall population prevalence was 4.57, 95% confidence interval (CI): 3.58, 5.76, and the estimated total number of CHB cases was about 3.3 million. The outcomes of the age-specific groups varied from 2.84, (95% CI: 2.60, 3.10) for the 0-14-year olds to 6.36 (95% CI: 5.83, 6.90) in the 25-34-year-old group. CONCLUSION: There are large age-group and regional differences in CHB prevalence in Turkey, where CHB remains a serious health problem

Deletion of Nedd4-2 results in progressive kidney disease in mice

NEDD4-2 (NEDD4L), a ubiquitin protein ligase of the Nedd4 family, is a key regulator of cell surface expression and activity of the amiloride-sensitive epithelial Na⁺ channel (ENaC). While hypomorphic alleles of Nedd4-2 in mice show salt-sensitive hypertension, complete knockout results in pulmonary distress and perinatal lethality due to increased cell surface levels of ENaC. We now show that Nedd4-2 deficiency in mice also results in an unexpected progressive kidney injury phenotype associated with elevated ENaC and Na⁺Cl⁻ cotransporter expression, increased Na⁺ reabsorption, hypertension and markedly reduced levels of aldosterone. The observed nephropathy is characterized by fibrosis, tubule epithelial cell apoptosis, dilated/cystic tubules, elevated expression of kidney injury markers and immune cell infiltration, characteristics reminiscent of human chronic kidney disease. Importantly, we demonstrate that the extent of kidney injury can be partially therapeutically ameliorated in mice with nephron-specific deletions of Nedd4-2 by blocking ENaC with amiloride. These results suggest that increased Na⁺ reabsorption via ENaC causes kidney injury and establish a novel role of NEDD4-2 in preventing Na⁺-induced nephropathy. Contrary to some recent reports, our data also indicate that ENaC is the primary in vivo target of NEDD4-2 and that Nedd4-2 deletion is associated with hypertension on a normal Na⁺ diet. These findings provide further insight into the critical function of NEDD4-2 in renal pathophysiology.Tanya L Henshall, Jantina A Manning, Omri S Alfassy, Pranay Goel, Natasha A Boase, Hiroshi Kawabe and Sharad Kuma

Seroprevalence of hepatitis B and C virus infections and risk factors in Turkey: a fieldwork TURHEP study

The present study was designed to determine the seroprevalence of hepatitis B and C virus (HBV, HCV) infections and risk factors in the Turkish general population. Participants were enrolled from urban and rural areas of the predetermined 23 EUROSTAT NUTS 2 region. A two-stage stratified sampling method was used to select participants from these regions (n = 5460; 50.9% females; mean (SD) age: 40.8 (14.7) years). Sociodemographics, clinical characteristics and risk factors were recorded at home visits. The seropositivity rates for hepatitis B surface antigen (HBsAg), anti-HCV, anti-HBs and anti-HBc total were 4.0%, 1.0%, 31.9% and 30.6%, respectively. Among HBsAg-positive cases, 94.5% were anti-HBe-positive, 70.2% were HBV-DNA-positive and 2.8% were anti-HDV total positive; 99.1% of HBV infections were of genotype D. Close contact with a hepatitis patient (OR 3.24; 95% CI 2.25-4.66; p = 50 years (OR 2; 95% CI 1.09-4.3; p 0.026) was the only significant predictor of anti-HCV positivity. In conclusion, our findings revealed an HBsAg positivity in 4% and anti-HCV positivity in 1% of the adult population and at least one-third of the population has been exposed to HBV infection in Turkey. Clinical Microbiology and Infection (C) 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved

Seroprevalence of hepatitis B and C virus infections and risk factors in Turkey: A fieldwork TURHEP study

PubMed ID: 26163105The present study was designed to determine the seroprevalence of hepatitis B and C virus (HBV, HCV) infections and risk factors in the Turkish general population. Participants were enrolled from urban and rural areas of the predetermined 23 EUROSTAT NUTS 2 region. A two-stage stratified sampling method was used to select participants from these regions (n = 5460; 50.9% females; mean (SD) age: 40.8 (14.7) years). Sociodemographics, clinical characteristics and risk factors were recorded at home visits. The seropositivity rates for hepatitis B surface antigen (HBsAg), anti-HCV, anti-HBs and anti-HBc total were 4.0%, 1.0%, 31.9% and 30.6%, respectively. Among HBsAg-positive cases, 94.5% were anti-HBe-positive, 70.2% were HBV-DNA-positive and 2.8% were anti-HDV total positive; 99.1% of HBV infections were of genotype D. Close contact with a hepatitis patient (OR 3.24; 95% CI 2.25-4.66; p < 0.001), living in the southeastern region (OR 2.74; 95% CI 1.7-4.45; p < 0.001), male gender (OR 1.77; 95% CI 1.28-2.46; p < 0.001), being married (OR 1.62; 95% CI 1.02-2.57; p 0.038), educational level less than high school (OR 1.53; 95% CI 1.04-2.26; p 0.03), orodental interventions (OR 1.54; 95% CI 1.01-2.35; p 0.047) and a history of non-disposable syringe use (OR 1.4; 95% CI 1.01-1.96; p 0.045) were significant determinants of HBsAg positivity. Age ?50 years (OR 2; 95% CI 1.09-4.3; p 0.026) was the only significant predictor of anti-HCV positivity. In conclusion, our findings revealed an HBsAg positivity in 4% and anti-HCV positivity in 1% of the adult population and at least one-third of the population has been exposed to HBV infection in Turkey. © 2015 European Society of Clinical Microbiology and Infectious Diseases.B100TSH0110005.9245 Gilead Sciences: 355728 British Microcirculation Society: Q-45-1397-08-42This study has been realized on behalf of the Turkish Association for the Study of the Liver. The study was funded in part by Gilead [ 355728 ], BMS [ Q-45-1397-08-42 ] and Roche Pharmaceuticals [ B100TSH0110005.9245 ]. The authors had complete access to the data that supports the publication. The authors would like to thank the OMEGA Contract Research Organization for conducting the field study, and Prof. Mustafa Serteser, Prof. Ibrahim Unsal, and Assoc. Prof. Isin Akyar, from Acibadem Labmed for the laboratory examinations. They also thank Prof. Sule Oktay, and Dr Cagla Ayhan, from KAPPA Consultancy Training Research Ltd (Istanbul, Turkey) for their support in manuscript preparation. -