World Health Organization Expert Working Group: Recommendations for assessing morbidity associated with enteric pathogens.

Abstract Background Diarrhoeal infections are one of the leading causes of child’s mortality and morbidity. Vaccines against Shigella, enterotoxigenic E. coli (ETEC), norovirus and invasive non-typhoidal Salmonella are in clinical development, however, their full value in terms of short and long-term health and socio-economic burden needs to be evaluated and communicated, to rationalise investment in vaccine development, and deployment. While estimates of mortality of enteric infections exist, the long-term morbidity estimates are scarce and have not been systematically collected. Methods The World Health Organization (WHO) has convened a Burden of Enteric Diseases Morbidity Working Group (BoED MWG) who identified key workstreams needed to characterise the morbidity burden of enteric infections. The group also identified four criteria for the prioritisation of pathogens of which impact on long-term morbidity needs to be assessed. Results The BoED MWG suggested to identify and analyse the individual level data from historical datasets to estimate the impact of enteric infections and confounders on long-term morbidity, including growth faltering and cognitive impairment in children (workstream 1); to conduct a systematic review of evidence on the association of aetiology specific diarrhoea with short- and long- term impact on growth, including stunting, and possibly cognitive impairment in children, while accounting for potential confounders (workstream 2); and to conduct a systematic review of evidence on the association of aetiology specific diarrhoea with short- and long- term impact on health outcomes in adults. The experts prioritised four pathogens for this work: Campylobacter jejuni, ETEC (LT or ST), norovirus (G1 or G2), and Shigella (dysenteriae, flexneri, sonnei). Conclusions The proposed work will contribute to improving the understanding of the impact of enteric pathogens on long-term morbidity. The timing of this work is critical as all four pathogens have vaccine candidates in the clinical pipeline and decisions about investments in development, manufacturing or vaccine procurement and use are expected to be made soon.