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  • In response to the lack of

    2019-05-06

    In response to the lack of epidemiological information on typhoid in Africa, the Typhoid Fever Surveillance in Africa Programme (TSAP), funded by the Bill & Melinda Gates Foundation and covering ten countries and 13 sites across Africa, was established between 2010 and 2014. In this buy LJI308 issue of , Florian Marks and colleagues present the results of a multicentre population-based surveillance study implemented by TSAP that uses standardised approaches based around blood culture, to provide an estimate of typhoid disease burden. Typhi, together with isolates of other non-typhoidal serovars (eg, Typhimurium, Enteritidis, Dublin) were the most common bacteria found in the blood at many of the sites, outstripping and A large variation existed in the adjusted incidence rates (AIR) of Typhi between the different sites, with no isolates at all in Sudan and Ethiopia but with estimated levels of 383 per 100 000 at one site in Burkina Faso. Typhoid was found in both young infants and in school age children, with higher AIR in children younger than 15 years old. Thus, the incidence of typhoid varied significantly between the sites, suggesting that the epidemiology is complex and potentially a highly variable patchwork exists across the region. Worryingly, significant levels of multidrug resistance were found in Typhi and in non-typhoidal at some of the sites. The establishment of these linked sites across Africa has the added bonus of providing an infrastructure for further studies on typhoid, but this system can also be potentially exploited for other studies on infectious diseases, antimicrobial resistance, or even non-communicable diseases. For example, the epidemiology of many of the non- bacteria isolated in the study (eg, Klebsiella) is poorly understood in the region. These data indicate that typhoid is a substantial disease burden in many parts of Africa, with the incidence levels likely to be an underestimate because of the difficulty of estimating true levels on the basis of microbial buy LJI308 culture. The report has encouraged the funding of TSAP to be continued for a further 2 years to gather more information, and these data, together with information from other sites, have prompted further funding into typhoid vaccine development and deployment. A key challenge is to determine how useful an efficacious vaccine might be in LMICs, where the levels of disease vary so greatly between different regions. Such studies might be pivotal to facilitate the deployment of such vaccines. In this regard, a need exists to develop economic models that provide governments and agencies with information that will inform decision making. The changing epidemiological pattern, the emergence of a potentially more aggressive multidrug resistant clade, and the likelihood of increased antibiotic usage in communities affected by the disease are creating a sense of urgency. Indeed, typhoid might prove to be a useful model of how to measure any benefit of vaccination on controlling the indiscriminate use of antibiotics. Other areas of interest will be the development of better diagnostics for the disease and the provision of proof that typhoid conjugate vaccines are as efficacious in different settings as the single efficacy study performed to date suggested.
    The recent devastating outbreak of Ebola virus disease led to the accelerated development of multiple candidate vaccines against this virus, with at least eight entering clinical trials in 2014–16. Direct evidence of 100% effectiveness against disease has been demonstrated for VSV-EBOV, a vaccine based on a replicating vesicular stomatitis virus genetically modified to express Ebola virus glycoprotein. This vaccine has been granted Breakthrough Therapy Designation status by the US Food and Drug Administration and PRIME status by the European Medicines Agency, and its single-dose regimen and proof of effectiveness from 10 days post-immunisation make it an attractive candidate for use in a responsive campaign (whether it be through ring immunisation around identified cases or as a whole-population intervention).