title: Re-analysis of health and educational impacts of a school-based deworming programme in western Kenya: a statistical replication of a cluster quasi-randomized stepped-wedge trial Population deworming every 6 months with albendazole in 1 million pre-school children in north India: DEVTA, a cluster-randomised trial
abstract: Introduction : Helminth ( worm ) infections cause morbidity among poor communities worldwide . An influential study conducted in Kenya in 1998–99 reported that a school-based drug- and -educational intervention had benefits for worm infections and school attendance . Methods : In this statistical replication , we re-analysed data from this cluster quasi-r and omized stepped-wedge trial , specifying two co- primary outcomes : school attendance and examination performance . We estimated intention-to-treat effects using year-stratified cluster- summary analysis and observation-level r and om-effects regression , and combined both years with a r and om-effects model accounting for year . The participants were not blinded to allocation status , and other interventions were concurrently conducted in a sub-set of schools . A protocol guiding outcome data collection was not available . Results : Quasi-r and omization result ed in three similar groups of 25 schools . There was a substantial amount of missing data . In year-stratified cluster- summary analysis , there was no clear evidence for improvement in either school attendance or examination performance . In year-stratified regression models , there was some evidence of improvement in school attendance [ adjusted odds ratios ( aOR ) : year 1 : 1.48 , 95 % confidence interval ( CI ) 0.88–2.52 , P = 0.147 ; year 2 : 1.23 , 95 % CI 1.01–1.51 , P = 0.044 ] , but not examination performance ( adjusted differences : year 1 : −0.135 , 95 % CI −0.323–0.054 , P = 0.161 ; year 2 : −0.017 , 95 % CI −0.201–0.166 , P = 0.854 ) . When both years were combined , there was strong evidence of an effect on attendance ( aOR 1.82 , 95 % CI 1.74–1.91 , P < 0.001 ) , but not examination performance ( adjusted difference −0.121 , 95 % CI −0.293–0.052 , P = 0.169 ) . Conclusions : The evidence supporting an improvement in school attendance differed by analysis method . This , and various other important limitations of the data , caution against over-interpretation of the results . We find that the study provides some evidence , but with high risk of bias , that a school-based drug-treatment and health-education intervention  improved school attendance and no evidence of effect on examination performance Summary 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-r and omised 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-r and omly 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 r and omly 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 Clinical Trials.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 ( st and ardised 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 )
target: Interestingly , the pure replication shows very similar impacts of the intervention on children in the intervention schools irrespective of whether they took the deworming medicine or not.7 For Miguel and colleagues , they term this as ‘ indirect within-school effects ’ of deworming , but equally the effects could be due to the non-specific effects of the health promotion interventions in the intervention schools .
  In addition , the study shows that allocation to the deworming group does not influence student progress , as the re- analysis shows clearly no evidence of a difference in examination performance between deworming and control groups.7,8 In the context of the global evidence base , there is only one other study that has examined school attendance with no obvious effect shown.4 Given all these uncertainties , we simply do n’t know if there is truly an effect on school attendance from the data , in taking all these factors into account formally in a GRADE analysis .4 But what weakens the case of deworming still further is that there is now quite good evidence of no effect for most of the main outcomes ( Figure 1 ) , including nutritional status , haemoglobin , cognition and school performance .
  This is important because without these effects it seems implausible that deworming itself would have an independent effect on school attendance or economic development .
background: The World Bank , the Gates Foundation and the World Health Organization promote national child deworming programmes in developing countries.1 They assert these programmes will improve nutritional status , health and school performance , and hence contribute to economic growth .
  Indeed , the World Health Organization states that deworming contributed to Japan ’s economic boom in the 1950s,2 and Nobel Laureates meeting in Copenhagen ranked deworming as the fourth most important intervention to solve the health problems of the whole world.3 Surprisingly , the evidence base for these cl aims from controlled studies is limited .
  Another trial in India showed benefit , but subsequent trials in the same area failed to show an effect.4,9 So deworming may have helped in these exceptional , heavily infected , untreated population s from another decade , but this is scarcely a solid base for contemporary policy : public health nutrition has changed , worm burden has declined and this probably accounts for the lack of effect on biomedical outcomes in contemporary studies .10 We have been perplexed by the un question ing belief behind deworming in the advocates , and have found it is deep rooted in American history .