Elderly age is not a negative predictive factor for virological response to therapy with pegylated interferon-α and ribavirin in chronic hepatitis C virus patients

BACKGROUND & AIMS: Age is frequently discussed as negative host factor to achieve a sustained virological response (SVR) to antiviral therapy of chronic hepatitis C. However, elderly patients often show advanced fibrosis/cirrhosis as known negative predictive factor. The aim of this study was to assess age as an independent predictive factor during antiviral therapy. METHODS: Overall, 516 hepatitis C patients were treated with pegylated interferon-α and ribavirin, thereof 66 patients ≥60 years. We analysed the impact of host factors (age, gender, fibrosis, haemoglobin, previous hepatitis C treatment) and viral factors (genotype, viral load) on SVR per therapy course by performing a generalized estimating equations (GEE) regression modelling, a matched pair analysis and a classification tree analysis. RESULTS: Overall, SVR per therapy course was 42.9 and 26.1%, respectively, in young and elderly patients with hepatitis C virus (HCV) genotypes 1/4/6. The corresponding figures for HCV genotypes 2/3 were 74.4 and 84%. In the GEE model, age had no significant influence on achieving SVR. In matched pair analysis, SVR was not different in young and elderly patients (54.2 and 55.9% respectively; P = 0.795 in binominal test). In classification tree analysis, age was not a relevant splitting variable. CONCLUSIONS: Age is not a significant predictive factor for achieving SVR, when relevant confounders are taken into account. As life expectancy in Western Europe at age 60 is more than 20 years, it is reasonable to treat chronic hepatitis C in selected elderly patients with relevant fibrosis or cirrhosis but without major concomitant diseases, as SVR improves survival and reduces carcinogenesis.

Recommendations for the Management of Hepatitis C Virus Infection Among People Who Inject Drugs

In the developed world, the majority of new and existing hepatitis C virus (HCV) infections occur among people who inject drugs (PWID). The burden of HCV-related liver disease in this group is increasing, but treatment uptake among PWID remains low. Among PWID, there are a number of barriers to care that should be considered and systematically addressed, but these barriers should not exclude PWID from HCV treatment. Furthermore, it has been clearly demonstrated that HCV treatment is safe and effective across a broad range of multidisciplinary healthcare settings. Given the burden of HCV-related disease among PWID, strategies to enhance HCV assessment and treatment in this group are urgently needed. These recommendations demonstrate that treatment among PWID is feasible and provides a framework for HCV assessment, management, and treatment. Further research is needed to evaluate strategies to enhance assessment, adherence, and SVR among PWID, particularly as new treatments for HCV infection become available.

Higher Risk of Incident HCV-Coinfections in MSM with a Wide HIV Transmission Bottleneck

BACKGROUND  High-risk sexual behaviors have been suggested as drivers of the recent dramatic increase of sexually-transmitted HCV among HIV-infected men who have sex with men(MSM). METHODS  We assessed the association between the HIV-transmission-bottleneck and the prevalence and incidence of HCV-coinfections in HIV-infected MSM from the Swiss-HIV-Cohort-Study(SHCS). As a proxy for the width of the transmission bottleneck we used the fraction of ambiguous nucleotides in Genotypic-Resistance-Tests(GRTs) from recent HIV-infections. We defined a broad bottleneck as a fraction of ambiguous nucleotides exceeding a previously-established threshold(0.5%). RESULTS  From the SHCS, we identified 671 MSMs with available HCV-serologies and with a HIV-GRT sampled during recent infection. Of those, 161(24.0%) exhibited a broad HIV-transmission-bottleneck, 38(5.7%) had at least one positive HCV test, and 26(3.9%) had an incident HCV infection. Individuals with broad HIV-transmission bottlenecks exhibited a twofold-higher odds of having ever experienced an HCV coinfection(OR[95%CI]=2.2[1.1, 4.3]) and a threefold-higher hazard of an incident HCV infection(HR[95%CI]= 3.0[1.4, 6.6]) than individuals with narrow HIV-transmission-bottlenecks. CONCLUSIONS  Our results indicate that the currently occurring sexual spread of HCV is focused on those MSMs that are prone to exhibit broad HIV-transmission-bottlenecks. This is consistent with an important role of high-risk behavior and mucosal-barrier-impairment in the transmission of HCV among MSM.

Diseases of the Tendons and Tendon Sheaths

Contracted flexor tendon leading to flexural deformity is a common congenital defect in cattle. Arthrogryposis is a congenital syndrome of persistent joint contracture that occurs frequently in Europe as a consequence of Schmallenberg virus infection of the dam. Spastic paresis has a hereditary component, and affected cattle should not be used for breeding purposes. The most common tendon avulsion involves the deep digital flexor tendon. Tendon disruptions may be successfully managed by tenorrhaphy and external coaptation or by external coaptation alone. Medical management alone is unlikely to be effective for purulent tenosynovitis.

Chronic hepatitis B virus coinfection is associated with renal impairment among Zambian HIV-infected adults.

Among 6789 HIV-infected Zambian adults screened for hepatitis B virus (HBV) coinfection, estimated glomerular filtration rate (eGFR) was 50-90 mL/minute/1.73 m(2) in 17.6% and <50 mL/minute/1.73 m(2) in 2.5%. Human immunodeficiency virus/HBV coinfection was associated with eGFR <50 mL/minute/1.73 m(2) (adjusted odds ratio, 1.96 [95% confidence interval, 1.34-2.86]), adjusted for age, sex, CD4(+) count, and World Health Organization disease stage.

An Outbreak of Porcine Reproductive and Respiratory Syndrome Virus in Switzerland Following Import of Boar Semen

An outbreak of porcine reproductive and respiratory syndrome virus (PRRSV) occurred in November 2012 in Switzerland (CH), traditionally PRRSV-free. It was detected after a German boar stud informed a semen importer about the detection of PRRSV during routine monitoring. Tracing of semen deliveries revealed 26 Swiss sow herds that had used semen from this stud after its last negative routine monitoring and 62 further contact herds. All herds were put under movement restrictions and examined serologically and virologically. As a first measure, 59 sows from five herds that had previously been inseminated with suspicious semen were slaughtered and tested immediately. Investigations in the stud resulted in 8 positive boars with recent semen deliveries to CH (Seven with antibodies and virus, one with antibodies only). In one boar out of six tested, virus was detected in semen. Of the 59 slaughtered sows, five from three herds were virus-positive. In one herd, the virus had spread, and all pigs were slaughtered or non-marketable animals euthanized. In the remaining herds, no further infections were detected. After confirmatory testings in all herds 3 weeks after the first examination gave negative results, restrictions were lifted in January 2013, and Switzerland regained its PRRSV-free status. The events demonstrate that import of semen from non-PRRS-free countries - even from negative studs - poses a risk, because monitoring protocols in boar studs are often insufficient to timely detect an infection, and infections of sows/herds occur even with low numbers of semen doses. The outbreak was eradicated successfully mainly due to the high disease awareness of the importer and because immediate actions were taken before clinical or laboratory diagnosis of a single case in the country was made. To minimize the risk of an introduction of PRRSV in the future, stricter import guidelines for boar semen have been implemented.

Metabolomics reveals that aldose reductase activity due to AKR1B10 is upregulated in hepatitis C virus infection

To understand the changes in the metabolome of hepatitis C virus (HCV)-infected persons, we conducted a metabolomic investigation in both plasma and urine of 30 HCV-positive individuals using plasmas from 30 HCV-negative blood donors and urines from 30 healthy volunteers. Samples were analysed by gas chromatography-mass spectrometry and data subjected to multivariate analysis. The plasma metabolomic phenotype of HCV-positive persons was found to have elevated glucose, mannose and oleamide, together with depressed plasma lactate. The urinary metabolomic phenotype of HCV-positive persons comprised reduced excretion of fructose and galactose combined with elevated urinary excretion of 6-deoxygalactose (fucose) and the polyols sorbitol, galactitol and xylitol. HCV-infected persons had elevated galactitol/galactose and sorbitol/glucose urinary ratios, which were highly correlated. These observations pointed to enhanced aldose reductase activity, and this was confirmed by real-time quantitative polymerase chain reaction with AKR1B10 gene expression elevated sixfold in the liver. In contrast, AKR1B1 gene expression was reduced 40% in HCV-positive livers. Interestingly, persons who were formerly HCV infected retained the metabolomic phenotype of HCV infection without reverting to the HCV-negative metabolomic phenotype. This suggests that the effects of HCV on hepatic metabolism may be long lived. Hepatic AKR1B10 has been reported to be elevated in hepatocellular carcinoma and in several premalignant liver diseases. It would appear that HCV infection alone increases AKR1B10 expression, which manifests itself as enhanced urinary excretion of polyols with reduced urinary excretion of their corresponding hexoses. What role the polyols play in hepatic pathophysiology of HCV infection and its sequelae is currently unknown.

First outbreak of sleeping disease in Switzerland: disease signs and virus characterization.

Sleeping disease is a contagious disease mainly of freshwater farmed rainbow trout, caused by salmonid alphavirus (SAV) Subtype 2. Here we describe the first case in Switzerland. Pathological changes ranged from acute pancreas necrosis to more chronic lesions with complete loss of exocrine pancreas and simultaneous degenerative, inflammatory and regenerative heart and muscle lesions. The partial sequencing of SAV E2 and nsp3 genes placed the Swiss SAV variant within the Subtype 2 clustering together with freshwater isolates from UK and continental Europe. Although mortality stayed low, growth rates were significantly reduced, making the disease economically relevant.

Serosurveillance of Schmallenberg virus in Switzerland using bulk tank milk samples.

Infections with Schmallenberg virus (SBV), a novel Orthobunyavirus transmitted by biting midges, can cause abortions and malformations of newborns and severe symptoms in adults of domestic and wild ruminants. Understanding the temporal and spatial distribution of the virus in a certain territory is important for the control and prevention of the disease. In this study, seroprevalence of antibodies against SBV and the spatial spread of the virus was investigated in Swiss dairy cattle applying a milk serology technique on bulk milk samples. The seroprevalence in cattle herds was significantly higher in December 2012 (99.5%) compared to July 2012 (19.7%). This high between-herd seroprevalence in cattle herds was observed shortly after the first detection of viral infections. Milk samples originating from farms with seropositive animals taken in December 2012 (n=209; mean 160%) revealed significantly higher S/P% ratios than samples collected in July 2012 (n=48; mean 103.6%). This finding suggests a high within-herd seroprevalence in infected herds which makes testing of bulk tank milk samples for the identification farms with past exposures to SBV a sensitive method. It suggests also that within-herd transmission followed by seroconversion still occurred between July and December. In July 2012, positive bulk tank milk samples were mainly restricted to the western part of Switzerland whereas in December 2012, all samples except one were positive. A spatial analysis revealed a separation of regions with and without positive farms in July 2012 and no spatial clustering within the regions with positive farms. In contrast to the spatial dispersion of bluetongue virus, a virus that is also transmitted by Culicoides midges, in 2008 in Switzerland, the spread of SBV occurred from the western to the eastern part of the country. The dispersed incursion of SBV took place in the western part of Switzerland and the virus spread rapidly to the remaining territory. This spatial pattern is consistent with the hypothesis that transmission by Culicoides midges was the main way of spreading.

Sheep persistently infected with Border disease readily transmit virus to calves seronegative to BVD virus.

Bovine viral diarrhea- and Border disease viruses of sheep belong to the highly diverse genus pestivirus of the Flaviviridae. Ruminant pestiviruses may infect a wide range of domestic and wild cloven-hooved mammals (artiodactyla). Due to its economic importance, programs to eradicate bovine viral diarrhea are a high priority in the cattle industry. By contrast, Border disease is not a target of eradication, although the Border disease virus is known to be capable of also infecting cattle. In this work, we compared single dose experimental inoculation of calves with Border disease virus with co-mingling of calves with sheep persistently infected with this virus. As indicated by seroconversion, infection was achieved only in one out of seven calves with a dose of Border disease virus that was previously shown to be successful in calves inoculated with BVD virus. By contrast, all calves kept together with persistently infected sheep readily became infected with Border disease virus. The ease of viral transmission from sheep to cattle and the antigenic similarity of bovine and ovine pestiviruses may become a problem for demonstrating freedom of BVD by serology in the cattle population.