Vibrio cholerae O1 transmission in Bangladesh: insights from a nationally representative serosurvey

Background: Pandemic Vibrio cholerae from cholera-endemic countries around the Bay of Bengal regularly seed epidemics globally. Without reducing cholera in these countries, including Bangladesh, global cholera control might never be achieved. Little is known about the geographical distribution and magnitude of V cholerae O1 transmission nationally. We aimed to describe infection risk across Bangladesh, making use of advances in cholera seroepidemiology, therefore overcoming many of the limitations of current clinic-based surveillance. Methods: We tested serum samples from a nationally representative serosurvey in Bangladesh with eight V cholerae-specific assays. Using these data with a machine-learning model previously validated within a cohort of confirmed cholera cases and their household contacts, we estimated the proportion of the population with evidence of infection by V cholerae O1 in the previous year (annual seroincidence) and used Bayesian geostatistical models to create high-resolution national maps of infection risk. Findings: Between Oct 16, 2015, and Jan 24, 2016, we obtained and tested serum samples from 2930 participants (707 households) in 70 communities across Bangladesh. We estimated national annual seroincidence of V cholerae O1 infection of 17·3% (95% CI 10·5–24·1). Our high-resolution maps showed large heterogeneity of infection risk, with community-level annual infection risk within the sampled population ranging from 4·3% to 62·9%. Across Bangladesh, we estimated that 28·1 (95% CI 17·1–39·2) million infections occurred in the year before the survey. Despite having an annual seroincidence of V cholerae O1 infection lower than much of Bangladesh, Dhaka (the capital of Bangladesh and largest city in the country) had 2·0 (95% CI 0·6–3·9) million infections during the same year, primarily because of its large population. Interpretation: Serosurveillance provides an avenue for identifying areas with high V cholerae O1 transmission and investigating key risk factors for infection across geographical scales. Serosurveillance could serve as an important method for countries to plan and monitor progress towards 2030 cholera elimination goals. Funding: The Bill & Melinda Gates Foundation, National Institutes of Health, and US Centers for Disease Control and Prevention

Simulations to Validate ATM Security Requirements and Concepts

Simulation zur Validierung von Anforderungen bzw. Konzepten mit Beispiel GAMMA-Projek

Different Transmembrane Domains Associate with Distinct Endoplasmic Reticulum Components during Membrane Integration of a Polytopic Protein

We have been studying the insertion of the seven transmembrane domain (TM) protein opsin to gain insights into how the multiple TMs of polytopic proteins are integrated at the endoplasmic reticulum (ER). We find that the ER components associated with the first and second TMs of the nascent opsin polypeptide chain are clearly distinct. The first TM (TM1) is adjacent to the α and β subunits of the Sec61 complex, and a novel component, a protein associated with the ER translocon of 10 kDa (PAT-10). The most striking characteristic of PAT-10 is that it remains adjacent to TM1 throughout the biogenesis and membrane integration of the full-length opsin polypeptide. TM2 is also found to be adjacent to Sec61α and Sec61β during its membrane integration. However, TM2 does not form any adducts with PAT-10; rather, a transient association with the TRAM protein is observed. We show that the association of PAT-10 with opsin TM1 does not require the N-glycosylation of the nascent chain and occurs irrespective of the amino acid sequence and transmembrane topology of TM1. We conclude that the precise makeup of the ER membrane insertion site can be distinct for the different transmembrane domains of a polytopic protein. We find that the environment of a particular TM can be influenced by both the “stage” of nascent chain biosynthesis reached, and the TM's relative location within the polypeptide

HIT-COVID, a global database tracking public health interventions to COVID-19

The COVID-19 pandemic has sparked unprecedented public health and social measures (PHSM) by national and local governments, including border restrictions, school closures, mandatory facemask use and stay at home orders. Quantifying the effectiveness of these interventions in reducing disease transmission is key to rational policy making in response to the current and future pandemics. In order to estimate the effectiveness of these interventions, detailed descriptions of their timelines, scale and scope are needed. The Health Intervention Tracking for COVID-19 (HIT-COVID) is a curated and standardized global database that catalogues the implementation and relaxation of COVID-19 related PHSM. With a team of over 200 volunteer contributors, we assembled policy timelines for a range of key PHSM aimed at reducing COVID-19 risk for the national and first administrative levels (e.g. provinces and states) globally, including details such as the degree of implementation and targeted populations. We continue to maintain and adapt this database to the changing COVID-19 landscape so it can serve as a resource for researchers and policymakers alike