The Typhoid Vaccine Acceleration Consortium (TyVAC): Vaccine effectiveness study designs: Accelerating the introduction of typhoid conjugate vaccines and reducing the global burden of enteric fever. Report from a meeting held on 26-27 October 2016, Oxford, UK

Typhoid fever is estimated to cause between 11.9–26.9 million infections globally each year with 129,000–216,510 deaths. Access to improved water sources have reduced disease incidence in parts of the world but the use of efficacious vaccines is seen as an important public health tool for countries with a high disease burden. A new generation of Vi typhoid conjugate vaccines (TCVs), licensed for use in young children and expected to provide longer lasting protection than previous vaccines, are now available. The WHO Strategic Advisory Group of Experts on Immunization (SAGE) has convened a working group to review the evidence on TCVs and produce an updated WHO position paper for all typhoid vaccines in 2018 that will inform Gavi, the Vaccine Alliance's future vaccine investment strategies for TCVs. The Typhoid Vaccine Acceleration Consortium (TyVAC) has been formed through a $36.9 million funding program from the Bill & Melinda Gates Foundation to accelerate the introduction of TCVs into Gavi-eligible countries. In October 2016, a meeting was held to initiate planning of TCV effectiveness studies that will provide the data required by policy makers and stakeholders to support decisions on TCV use in countries with a high typhoid burden. Discussion topics included (1) the latest evidence and data gaps in typhoid epidemiology; (2) WHO and Gavi methods and data requirements; (3) data on TCV efficacy; (4) cost effectiveness analysis for TCVs from mathematical models; (5) TCV delivery and effectiveness study design. Specifically, participants were asked to comment on study design in 3 sites for which population-based typhoid surveillance is underway. The conclusion of the meeting was that country-level decision making would best be informed by the respective selected sites in Africa and Asia vaccinating children aged from 9-months to 15-years-old, employing either an individual or cluster randomized design with design influenced by population characteristics, transmission dynamics, and statistical considerations

Genomic analysis of clinical Aeromonas isolates reveals genetic diversity but little evidence of genetic determinants for diarrhoeal disease

Aeromonas spp. are associated with a number of infectious syndromes in humans including gastroenteritis and dysentery. Our understanding of the genetic diversity, population structure, virulence determinants and antimicrobial resistance of the genus has been limited by a lack of sequenced genomes linked to metadata. We performed a comprehensive analysis of the whole genome sequences of 447 Aeromonas isolates from children in Karachi, Pakistan, with moderate-to-severe diarrhoea (MSD) and from matched controls without diarrhoea that were collected as part of the Global Enteric Multicenter Study (GEMS). Human-associated Aeromonas isolates exhibited high species diversity and extensive antimicrobial and virulence gene content. Aeromonas caviae, A. dhankensis, A. veronii and A. enteropelogenes were all significantly associated with MSD in at least one cohort group. The maf2 and lafT genes that encode components of polar and lateral flagella, respectively, exhibited a weak association with isolates originating from cases of gastroenteritis