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

Abstract

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.

Funding: UK Medical Research Council, USAID, World Bank (albendazole donated by GlaxoSmithKline).

Figure 1

Location of the seven DEVTA study districts in the state of Uttar Pradesh in north India 1 Lucknow (study centre: Lucknow city), 2 Rae Bareli, 3 Unnao, 4 Kanpur, 5 Hardoi, 6 Lakhimpur, 7 Sitapur. Within the districts, the study areas were largely rural.

Figure 2

Flow diagram for the 72 mainly rural administrative blocks randomly allocated five years of six-monthly albendazole or open control AWC: anganwadi (ie, courtyard) child-care centre. In these 72 blocks, 8338 child-care centres were followed up, with a total population at ages 1·0–6·0 years of 1 million at any one time (hence 2 million ever in the study, May, 1999–April, 2004). *AWC catchment areas correspond approximately to villages; it was determined before randomisation which AWCs were then functional, and hence potential study areas; loss of an AWC to follow-up was defined by having only 1–6 follow-up visits (mean only 3, as against 12 in included AWCs), and was generally because the AWC had ceased to function.

Figure 3

Correlation between 72 block-specific average numbers of infant and child deaths per child-care centre (AWC) during the entire study The inter-block correlation (illustrated here) between numbers of infant and child deaths per AWC was 68·7% ignoring trial treatment allocation (or 68·4% given the four-way allocation to albendazole, retinol, both, or neither), and ranged from 66–71% within the four treatment groups. Mortality at ages 0–6 months had correlation 99·3% with infant and 68·2% with child mortality.