Burden of <i>Shigella</i> and enterotoxigenic <i>Escherichia coli</i> infections among children under 5 years in Ethiopia, Kenya and Malawi: a systematic review and meta-analysis

Diarrhoea remains a major problem among children in low- and middle-income countries, driven by multiple pathogens including rotavirus, <i>Shigella</i> and enterotoxigenic <i>Escherichia coli</i> (ETEC). Rotavirus vaccines have notably reduced diarrhoea deaths. However, the health consequences associated with <i>Shigella</i> and ETEC, along with rising antimicrobial resistance (AMR), have prompted the WHO to prioritise vaccine development against these two pathogens. Understanding their disease burden is crucial for guiding this effort and informing preparedness for vaccine adoption.We conducted a systematic review and meta-analysis of primary peer-reviewed literature to establish the prevalence, subtypes and AMR patterns of <i>Shigella</i> and ETEC-associated diarrhoea in Ethiopia, Kenya and Malawi, where the authors have established a multidisciplinary research programme addressing gastrointestinal infections. We searched in PubMed, among other databases, for English-language publications from 1 January 2000 to 28 July 2023. The meta-analysis used a random effects model to estimate pooled prevalence.43 studies were included. Malawi exhibited a higher estimated prevalence of <i>Shigella</i> (24% (95% CI 10% to 39%)) than Ethiopia and Kenya (both with an estimated prevalence of 6%), most likely explained by the application of sensitive, molecular detection methods in Malawi. The overall pooled prevalence of <i>Shigella</i> was 8% (95% CI 6% to 9%). Malawi again displayed higher ETEC prevalence (24% (95% CI 14% to 33%)) compared with Kenya (7% (95% CI 5% to 10%)), with no studies of ETEC identified from Ethiopia. The overall pooled prevalence of ETEC was 11% (95% CI 6% to 15%). <i>Shigella flexneri</i> was the major species of <i>Shigella,</i> and heat-stable ETEC was highly prevalent. <i>Shigella</i> species displayed resistance to several classes of antibiotics, including penicillins, tetracyclines, macrolides and sulphonamides, but susceptibility to fluoroquinolones and cephalosporins.These findings underscore the need for countries to generate updated disease burden estimates for <i>Shigella</i> and ETEC through epidemiologically robust studies that use sensitive diagnostic methods in preparation for vaccine introduction.