Seroprevalence and risk factors of recent infection with hepatitis E virus during an acute outbreak in an urban setting in Chad, 2017.

BACKGROUND: From September 2016-April 2017, Am Timan, Chad, experienced a large HEV outbreak in an urban setting with a limited impact in terms of morbidity and mortality. To better understand HEV epidemiology in this context, we estimated the seroprevalence of anti-HEV antibodies (IgM and IgG) and assessed the risk factors for recent HEV infections (positive anti-HEV IgM) during this outbreak. METHODS: A serological survey using simple random sampling was implemented in Am Timan at the tail-end of the outbreak (sample size aim = 384 household). Household members provided us with blood samples and household heads answered questions around water, sanitation and hygiene practices and animal ownership. Blood samples were tested for HEV IgG and IgM antibodies using Enzyme-Immune-Assay (EIA). We calculated weighted prevalence estimates and prevalence ratios (PRs) for possible risk factors for recent infection using multivariate Cox regression. RESULTS: We included 241 households (1529 participants). IgM prevalence decreased with age: 12.6% (< 5 years) to 4.3% (> 15 years). IgG prevalence increased with age: 23.5% (< 5 years) to 75.9% (> 15 years). Risk factors for recent HEV infections included: sharing the sanitation facility with other HHs (PR 1.72; 95%CI: 1.08-2.73), not systematically using soap for HW (PR 1.85; 95%CI: 1.30-2.63) and having animals sleeping inside the compound (PR 1.69; 95%CI: 1.15-2.50). CONCLUSIONS: Evidence suggests that Am Timan was already highly endemic for HEV before the outbreak, potentially explaining the limited extent of the outbreak. Recent infection with HEV was linked to household level exposures. Future HEV outbreak response must include ensuring access to safe water, and reducing household level transmission through active hygiene and sanitation promotion activities.

A large outbreak of Hepatitis E virus genotype 1 infection in an urban setting in Chad likely linked to household level transmission factors, 2016-2017.

BACKGROUND: In September 2016, three acutely jaundiced (AJS) pregnant women were admitted to Am Timan Hospital, eastern Chad. We described the outbreak and conducted a case test-negative study to identify risk factors for this genotype of HEV in an acute outbreak setting. METHODS: Active case finding using a community based surveillance network identified suspected AJS cases. Pregnant or visibly ill AJS cases presenting at hospital were tested with Assure® IgM HEV rapid diagnostic tests (RDTs) and some with Polymerase Chain Reaction (PCR) in Amsterdam; confirmed cases were RDT-positive and controls were RDT-negative. All answered questions around: demographics, household makeup, area of residence, handwashing practices, water collection behaviour and clinical presentation. We calculated unadjusted odds ratios (ORs) and 95% confidence intervals (95% CI). RESULTS: Between September and April 2017, 1443 AJS cases (1293 confirmed) were detected in the town(attack rate: 2%; estimated 65,000 population). PCR testing confirmed HEV genotype 1e. HEV RDTs were used for 250 AJS cases; 100 (40%) were confirmed. Risk factors for HEV infection, included: having at least two children under the age of 5 years (OR 2.1, 95%CI 1.1-4.3), having another household member with jaundice (OR 2.4, 95%CI 0.90-6.3) and, with borderline significance, living in the neighbourhoods of Riad (OR 3.8, 95%CI 1.0-1.8) or Ridina (OR 3.3, 95%CI 1.0-12.6). Cases were more likely to present with vomiting (OR 3.2, 9%CI 1.4-7.9) than controls; possibly due to selection bias. Cases were non-significantly less likely to report always washing hands before meals compared with controls (OR 0.33, 95%CI 0.1-1.1). DISCUSSION: Our study suggests household factors and area of residence (possibly linked to access to water and sanitation) play a role in HEV transmission; which could inform future outbreak responses. Ongoing sero-prevalence studies will elucidate more aspects of transmission dynamics of this virus with genotype 1e.

Circadian control of fatty acid elongation by SIRT1 protein-mediated deacetylation of acetyl-coenzyme A synthetase 1.

The circadian clock regulates a wide range of physiological and metabolic processes, and its disruption leads to metabolic disorders such as diabetes and obesity. Accumulating evidence reveals that the circadian clock regulates levels of metabolites that, in turn, may regulate the clock. Here we demonstrate that the circadian clock regulates the intracellular levels of acetyl-CoA by modulating the enzymatic activity of acetyl-CoA Synthetase 1 (AceCS1). Acetylation of AceCS1 controls the activity of the enzyme. We show that acetylation of AceCS1 is cyclic and that its rhythmicity requires a functional circadian clock and the NAD(+)-dependent deacetylase SIRT1. Cyclic acetylation of AceCS1 contributes to the rhythmicity of acetyl-CoA levels both in vivo and in cultured cells. Down-regulation of AceCS1 causes a significant decrease in the cellular acetyl-CoA pool, leading to reduction in circadian changes in fatty acid elongation. Thus, a nontranscriptional, enzymatic loop is governed by the circadian clock to control acetyl-CoA levels and fatty acid synthesis.

Isolation and quantification of chitin-binding mistletoe lectin from mistletoe extracts and validation of this method.

A method was established to isolate and quantify small amounts of chitin-binding mistletoe lectin (cbML) from extracts of the mistletoe (Viscum album L.) by affinity and reverse phase high performance liquid chromatography. A validation, according to ICH guidelines, of this analytical method was carried out and showed that specificity, robustness and precision are guaranteed. In addition, linearity is ensured for a content between 0.6 and 4.1 microg/ml of cbML in the extracts and recovery was calculated to be in the range of 94 to 100%. So, accuracy of the method is guaranteed as well. As far as the range of the analytical method is concerned, a minimum of 1.2 microg and a maximum of 8.2 microg cbML can be incubated with the affinity material. Detection and quantitation limits were calculated to be 0.13 and 0.46 microg/ml cbML, respectively.