Suchergebnisse

Typhoid fever illnesses are responsible for more than 100 000 deaths worldwide each year. In Bangladesh, typhoid fever is endemic, with incidence rates between 292-395 per 100 000 people annually. While considerable effort has been made to improve access to clean water and sanitation services in the country, there is still a significant annual typhoid burden, which particularly affects children. A typhoid conjugate vaccine (Vi-TCV) was recently prequalified by the World Health Organization and recommended for use, and offers the potential to greatly reduce the typhoid burden in Bangladesh. This study is a double-blind, cluster-randomized, controlled trial of Vi-TCV in a geographically defined area in Dhaka, Bangladesh. At least 32 500 children from 9 months to <16 years of age will be vaccinated and followed for 2 years to assess the effectiveness and safety of Vi-TCV in a real-world setting. All cluster residents will also be followed to measure the indirect effect of Vi-TCV in this community. This protocol has been approved by the International Centre for Diarrhoeal Disease Research, Bangladesh; a University of Oxford research review; and both ethical review committees. Informed written consent and assent will be obtained before enrollment. Vi-TCV has been shown to be safe and effective in previous, smaller-scale studies. The results of this study will be shared through a series of peer-reviewed journal articles. The findings will also be disseminated to the local government, stakeholders within the community, and the population within which the study was conducted. This trial is the largest and only cluster-randomized control trial of Vi-TCV ever conducted, and will describe the effectiveness of Vi-TCV in an endemic population. The results of this trial may provide important evidence to support the introduction of TCVs in countries with a high burden of typhoid. ISRCTN11643110.

Genomics, combined with population mobility data, used to map importation and spatial spread of SARS-CoV-2 in high-income countries has enabled the implementation of local control measures. Here, to track the spread of SARS-CoV-2 lineages in Bangladesh at the national level, we analysed outbreak trajectory and variant emergence using genomics, Facebook 'Data for Good' and data from three mobile phone operators. We sequenced the complete genomes of 67 SARS-CoV-2 samples (collected by the IEDCR in Bangladesh between March and July 2020) and combined these data with 324 publicly available Global Initiative on Sharing All Influenza Data (GISAID) SARS-CoV-2 genomes from Bangladesh at that time. We found that most (85%) of the sequenced isolates were Pango lineage B.1.1.25 (58%), B.1.1 (19%) or B.1.36 (8%) in early-mid 2020. Bayesian time-scaled phylogenetic analysis predicted that SARS-CoV-2 first emerged during mid-February in Bangladesh, from abroad, with the first case of coronavirus disease 2019 (COVID-19) reported on 8 March 2020. At the end of March 2020, three discrete lineages expanded and spread clonally across Bangladesh. The shifting pattern of viral diversity in Bangladesh, combined with the mobility data, revealed that the mass migration of people from cities to rural areas at the end of March, followed by frequent travel between Dhaka (the capital of Bangladesh) and the rest of the country, disseminated three dominant viral lineages. Further analysis of an additional 85 genomes (November 2020 to April 2021) found that importation of variant of concern Beta (B.1.351) had occurred and that Beta had become dominant in Dhaka. Our interpretation that population mobility out of Dhaka, and travel from urban hotspots to rural areas, disseminated lineages in Bangladesh in the first wave continues to inform government policies to control national case numbers by limiting within-country travel.

Typhoid fever remains a significant health problem in sub‐Saharan Africa, with incidence rates of >100 cases per 100,000 person‐years of observation. Despite the prequalification of safe and effective typhoid conjugate vaccines (TCV), some uncertainties remain around future demand. Real‐life effectiveness data, which inform public health programs on the impact of TCVs in reducing typhoid‐related mortality and morbidity, from an African setting may help encourage the introduction of TCVs in high‐burden settings. Here, we describe a cluster‐randomized trial to investigate population‐level protection of TYPBAR‐TCV®, a Vi‐polysaccharide conjugated to a tetanus‐toxoid protein carrier (Vi‐TT) against blood‐culture‐confirmed typhoid fever, and the synthesis of health economic evidence to inform policy decisions. A total of 80 geographically distinct clusters are delineated within the Agogo district of the Asante Akim region in Ghana. Clusters are randomized to the intervention arm receiving Vi‐TT or a control arm receiving the meningococcal A conjugate vaccine. The primary study endpoint is the total protection of Vi‐TT against blood‐culture‐confirmed typhoid fever. Total, direct, and indirect protection are measured as secondary outcomes. Blood‐culture‐based enhanced surveillance enables the estimation of incidence rates in the intervention and control clusters. Evaluation of the real‐world impact of TCVs and evidence synthesis improve the uptake of prequalified/licensed safe and effective typhoid vaccines in public health programs of high burden settings. This trial is registered at the Pan African Clinical Trial Registry, accessible at Pan African Clinical Trials Registry (ID: PACTR202011804563392). © 2021 by the authors. ; Funding: This research funded as part of the EDCTP2 programme supported by the European Union (RIA2017S-2027) and as a grant from the Bill & Melinda Gates Foundation (OPP1205877). Disclaimer: This manuscript reflects only the authors' view and does not necessarily represent the official ...