TARGET · TARGET: Targeted antibiotic therapy for high-risk children with watery diarrhoea and malnutrition

BACKGROUND: Diarrhoea is an important cause of morbidity and mortality in children under 5, especially in SSA. WHO guidelines do not recommend antibiotics for acute watery diarrhoea, while 25-50% of watery diarrhoea episodes are caused by bacteria. Children with co-morbid malnutrition and watery diarrhoea are more likely to have bacterial aetiology and poor outcomes. We hypothesize that the benefits of appropriate antibiotic treatment for these children are greater than the associated risks.AIM: TARGET aims to generate evidence on how improved management and treatment of watery diarrhoea in children with malnutrition can reduce childhood morbidity and mortality, and support implementation of this evidence across SSA, now and in a climate-uncertain future.APPROACH: Central to our approach is a clinical trial evaluating the benefit of two antibiotic treatments for watery diarrhoea in children with malnutrition in Kenya and Tanzania. We will assess the characteristics of children who most benefit from therapy and estimate generalizability of the observed effects to other vulnerable populations and under future climate scenarios. We will evaluate the risk-benefit trade-off with the development of antimicrobial resistance and assess provider perspectives on antibiotic use and clinical guidelines. In our dissemination, we focus on uptake in WHO guidelines and policy translation. A critical focus of the project is the development of capacity for leadership of multisite clinical trials focused on enteric infections at KEMRI (Kenya) and HGHRI (Tanzania).IMPACT: Our late-stage clinical data will directly inform guidelines for treating children with watery diarrhoea and malnutrition and contribute to timely identification of vulnerable children. This has potential to reduce childhood deaths and repeat hospitalization. Importantly, TARGET will contribute to leadership of our SSA partners in future clinical trials, funding applications, impactful research, and publications.