The impact of improved water, sanitation and hygiene on oral rotavirus vaccine immunogenicity in Zimbabwean infants: sub-study of a cluster-randomized trial.

BACKGROUND: Oral vaccines have lower efficacy in developing compared to developed countries. Poor water, sanitation and hygiene (WASH) may contribute to reduced oral vaccine immunogenicity. METHODS: We conducted a cluster-randomized 2x2 factorial trial in rural Zimbabwe (NCT01824940). Pregnant women and their infants were eligible if they lived in clusters randomized to: 1) Standard-of-care (52 clusters); 2) Improved infant feeding (53 clusters); 3) WASH: ventilated improved pit latrine, two hand-washing stations, liquid soap, chlorine, infant play space, hygiene counseling (53 clusters); or 4) Feeding+WASH (53 clusters). This sub-study compared oral rotavirus vaccine seroconversion (primary outcome), and seropositivity and geometric mean titre (GMT) (secondary outcomes), in WASH versus non-WASH infants by intention-to-treat analysis. RESULTS: We included 801 infants with documented rotavirus vaccine receipt and post-vaccine titre measurements (329 from 84 WASH clusters; 472 from 102 non-WASH clusters); 328 infants with pre-vaccination titres were included in the primary outcome. 33/109 (30.3%) infants in the WASH group seroconverted following rotavirus vaccination, compared to 43/219 (19.6%) in the non-WASH group (absolute difference 10.6% (95%CI 0.54, 20.7); p=0.031). In the WASH versus non-WASH groups, 90/329 (27.4%) versus 107/472 (22.7%) were seropositive post-vaccination (absolute difference 4.7% (95%CI -1.4, 10.8; p=0.130) and anti-rotavirus GMT was 18.4U/mL (95% CI 15.6, 21.7) versus 14.9U/mL (95% CI 13.2, 16.8); p=0.072. After restricting analyses to infants who received both doses of rotavirus vaccine, the effect of WASH on seroconversion was greater (absolute difference 13.7% (95%CI 2.0, 25.4); p=0.016). CONCLUSIONS: Improvements in household WASH led to modest but significant increases in seroconversion to oral rotavirus vaccine in rural Zimbabwean infants.Wellcome Trust [203905/Z/16/Z, 093768/Z/10/Z and 108065/Z/15/Z )Bill and Melinda Gates Foundation [OPP1021542 and OPP113707]UK Department for International Development (UK Aid)Swiss Agency for Development and CooperationUS National Institutes of Health [2R01HD060338-06