PRoRota · SAFETY, EFFECTIVENESS AND COST-EFFECTIVENESS OF PROBIOTICS AS ADJUNCT PREVENTIVE THERAPY FOR CHILDHOOD DIARRHOEA AND ANTIMICROBIAL RESISTANCE IN AFRICA: A DOUBLE BLINDED RANDOMIZED CONTROLLED TRIAL

While rotavirus vaccines have reduced the incidence of childhood diarrhoea, their efficacies remain significantly lower in developing countries compared to high-income countries. One plausible factor is the disrupted gut microbiome among children in low-medium income countries (LMIC) settings. Our hypothesis is that probiotics can improve a destabilized gut microbiome, thereby improving vaccine immune responses, particularly oral vaccines such as rotavirus vaccines and treatment outcomes. We hypothesize that the provision of probiotics to infants from birth to one month and 4-weekly booster doses of probiotics, given as an adjunct to rotavirus vaccination and Water, Sanitation, and Hygiene (WASH) education, can reduce all-cause diarrhoea in infants. We will conduct a double-blind, placebo-controlled trial in 4000 newborns across Tanzania, Malawi, and Côte d'Ivoire. Infants will be randomized to receive probiotic or placebo boosters at 6, 10, and 14 weeks of age and followed until 6 months to measure diarrhoea incidence (primary outcome), immune response to the rotavirus vaccine, and risk of multidrug-resistant bacterial gut colonization (secondary outcomes). The intervention's safety, cost-effectiveness, and acceptability will also be evaluated. We shall also embed formative research that will assist us in designing enhanced WASH programs and use climate and diarrhoea disease burden to model predictive early warning systems. We anticipate that the findings from this 4-year project will directly inform global health policy, leading to improved rotavirus vaccine efficacy in LMICs. This will contribute to a significant reduction in diarrhoeal diseases and the risk of antimicrobial resistance (AMR), while also enabling the creation of early-warning systems for outbreak prediction. Additionally, the initiative will foster interdisciplinary research capacity and strengthening collaboration among partners.