Population deworming every 6 months with albendazole in 1 million pre-school children in north India: DEVTA, a cluster-randomised trial

Background In north India many pre-school children are underweight, many have intestinal worms, and 2-3% die at ages 1.0-6.0 years. We used the state-wide Integrated Child Development Service (ICDS) infrastructure to help to assess any effects of regular deworming on mortality. Methods Participants in this cluster-randomised study were children in catchment areas of 8338 ICDS-staffed village child-care centres (under-5 population 1 million) in 72 administrative blocks. Groups of four neighbouring blocks were cluster-randomly allocated in Oxford between 6-monthly vitamin A (retinol capsule of 200 000 IU retinyl acetate in oil, to be cut and dripped into the child's mouth every 6 months), albendazole (400 mg tablet every 6 months), both, or neither (open control). Analyses of albendazole effects are by block (36 vs 36 clusters). The study spanned 5 calendar years, with 11 6-monthly mass-treatment days for all children then aged 6-72 months. Annually, one centre per block was randomly selected and visited by a study team 1-5 months after any trial deworming to sample faeces (for presence of worm eggs, reliably assessed only after mid-study), weigh children, and interview caregivers. Separately, all 8338 centres were visited every 6 months to monitor pre-school deaths (100 000 visits, 25 000 deaths at age 1.0-6.0 years [the primary outcome]). This trial is registered at ClinicalTrials.gov, NCT00222547. Findings Estimated compliance with 6-monthly albendazole was 86%. Among 2589 versus 2576 children surveyed during the second half of the study, nematode egg prevalence was 16% versus 36%, and most infection was light. After at least 2 years of treatment, weight at ages 3.0-6.0 years (standardised to age 4.0 years, 50% male) was 12.72 kg albendazole versus 12.68 kg control (difference 0.04 kg, 95% CI -0.14 to 0.21, p=0.66). Comparing the 36 albendazole-allocated versus 36 control blocks in analyses of the primary outcome, deaths per child-care centre at ages 1.0-6.0 years during the 5-year study were 3.00 (SE 0.07) albendazole versus 3.16 (SE 0.09) control, difference 0.16 (SE 0.11, mortality ratio 0.95, 95% CI 0.89 to 1.02, p=0.16), suggesting absolute risks of dying between ages 1.0 and 6.0 years of roughly 2.5% albendazole versus 2.6% control. No specific cause of death was significantly affected. Interpretation Existing ICDS village staff can be organised to deliver simple pre-school interventions sustainably for many years at low cost, but regular deworming had little effect on mortality in this lightly infected pre-school population.