Deworming and adjuvant interventions for improving the developmental health and well‐being of children in low‐ and middle‐income countries: a systematic review and network meta‐analysis

Abstract

This review evaluates the effects of mass deworming for soil‐transmitted helminths on growth, educational achievement, cognition, school attendance, quality of life and adverse effects in children in endemic helminth areas. Mass deworming for soil‐transmitted helminths probably has little to no effect on weight, height, school attendance, cognition measured by short‐term attention, or mortality. There are no data on short‐term quality of life and little evidence of adverse effects. Mass deworming for schistosomiasis alone may slightly increase weight but probably has little to no effect on height and cognition. The evidence does not support indirect benefits for untreated children from being exposed to treated children. One moderate quality long term study showed an increase in economic productivity (hours worked) and increase in educational enrollment 10 years later of mass deworming and hygiene promotion. But, it is uncertain whether these effects are due to the deworming or the combined hygiene intervention. Findings are consistent for various groups of the population by age, gender, worm prevalence, baseline nutritional status, compliance, impact on worms, infection intensity, types of worms, risk of bias, and study characteristics. Deworming for children who screened positive for schistosomiasis or soil‐transmitted helminths results in larger gains in weight but no difference in effect on height, cognition or school attendance. Also, one low to moderate quality study showed long‐term benefit on school enrolment of sanitation improvement combined with screening and treating people for hookworm infection. Abstract Background Soil‐transmitted helminthiasis and schistosomiasis, considered among the neglected tropical diseases by the World Health Organization (WHO), affect more than a third of the world's population, with varying intensity of infection. There is debate about the effectiveness and cost‐effectiveness of mass deworming of children as a strategy to improve child health in endemic areas. Objectives The objective of this review was to evaluate the effects of mass deworming for soil‐transmitted helminths with or without deworming for schistosomiasis or co‐interventions on growth, educational achievement, cognition, school attendance, quality of life and adverse effects in children inendemic helminth areas. We also aimed to assess possible effect modifiers using pre‐planned subgroup analysis of age, sex, prevalence of worms and baseline nutritional status. Search strategy Our librarian scientist designed a search strategy that was reviewed by the Campbell Collaboration librarian for the following 11 electronic databases: MEDLINE, CINAHL, LILACS, EMBASE, the Cochrane Library, Econlit, Internet Documents in Economics Access Service (IDEAS), Public Affairs Information Service (PAIS), Social Services Abstracts, Global Health CABI and CAB Abstracts, up to May 13, 2015. We also searched websites and clinical trial registers, other systematic reviews, and contacted authors and experts in the field. Study selection criteria We included studies if they included children aged six months to 16 years, carried out mass deworming for soil‐transmitted helminths (alone or in combination with other drugs or child health interventions), reported one of our primary outcomes of growth, school attendance, school performance, cognitive processing or development, well‐being, or adverse events, and included a comparator to a control or active comparator. We included randomized trials, quasi‐randomized trials, controlled before after studies, interrupted time series and quasi‐experimental studies that used statistical methods of analysis to match participants with non‐participants, or statistical methods to account for confounding and sample selection bias. Data collection and analysis We screened titles and abstracts in duplicate, as well as the full texts of those considered eligible at level 1. We used a pre‐tested data extraction form to collect details on participants, interventions, outcomes, study methods and setting, and extracted data in duplicate. We conducted random effects pairwise meta‐analysis for all primary outcomes. If heterogeneity was acceptable (I²<75%), we conducted random effects, Bayesian network meta‐analysis to compare different drugs and combinations of interventions, using WinBugs. We assessed risk of bias with the Cochrane risk of bias tool or the Campbell International Development review group tool, as appropriate. We assessed GRADE certainty of evidence for each outcome using the GRADE Working Group methods. Results We analysed 65 studies with a duration from four months to five years (median 12 months) with 1,092,120 children and five long‐term studies eight to 10 years after mass deworming programmes with >90,000 children. These studies were conducted in 23 low and middle income countries (L&MICs), in areas where prevalence of worms ranged from 0.5 per cent to 99 per cent infected. Most of the studies consisted of deworming twice per year or more frequently, with only two studies deworming once per year. Overall risk of bias was moderate. Mass deworming for soil‐transmitted helminths compared to controls probably has little to no improvement in weight (0.09 kg, 95%CI: ‐0·04 to 0·2; 35,430 participants, 11 trials), height (0.07 cm, 95% CI:‐0.1 cm to 0.24 cm); 6,839 participants, nine trials) or attendance (1% higher, 95% CI: ‐1% to 3%; >30,000 participants, seven trials) (moderate certainty evidence). Mass deworming for soil transmitted helminths leads to little to no difference in proportion stunted (eight per 1000 fewer‐from 48 fewer to 32 more; 4,286 participants, four trials), cognition measured by short‐term attention (‐0·23 points on 100 point scale, 95%CI ‐0·6, 0·14; 4,078 participants, three trials), or mortality (1 per 1000 fewer, 95%CI: ‐3 to 1 per 1000; >1 million participants, six trials) (high certainty evidence). We found no data on short‐term quality of life and little evidence of adverse effects. Mass deworming for schistosomiasis alone may slightly increase weight (0·4 kg, 95%CI: ‐0·2, 1·0) and has little to no effect on height (low certainty evidence) and cognition (moderate certainty evidence). Our analyses do not support indirect benefits for untreated children, from being exposed to treated children in the community (low certainty evidence). There may be increase in long‐term economic productivity (1.58 hours more per week, 95%CI: ‐0.46 to 3.62) and school enrolment (0.29 years, 95%CI 0.01 to 0.58), little to no effect on height (‐0.11 cm, 95%CI: ‐0.64 to 0.42) and self‐reported health (0.04 units, 95%CI: 0.0 to 0.08) of mass deworming when combined with hygiene education, however, it is uncertain whether these effects are due to deworming alone or hygiene or the combination (very low certainty). We are uncertain about long‐term effects on math or English at school and cognitive development due to very low certainty evidence.. Results were congruentacross sensitivity and subgroup analyses by age, sex, worm prevalence, baseline nutritional status, impact on worms, infection intensity, types of worms (ascaris, hookworm or trichuris), risk of bias, cluster vs. individual trials, high compliance and low attrition bias. Deworming for children who screened positive for schistosomiasis or soil‐transmitted helminths resulted in larger gains in weight and no difference in effect on height, cognition or school attendance. Implications for policy and programmes This independent analysis reinforces the case against mass deworming. These findings suggest that in addition to a reconsideration of mass deworming programmes in their current form, additional policy options need to be explored to improve child health and nutrition in worm‐endemic areas. These include the needs for investing in interventions to address basic determinants of worm infestations such as poverty, living conditions, sanitation and inequities. Decisions on public health approaches in such settings need to be taken on the basis of human rights, ethics and evidence‐based, sustainable cost‐effective approaches. For schistosomiasis, the policy implication is that mass deworming may be effective at improving weight. Implications for research Since all analyses of effect modification are limited by aggregate level data which may hide individual level differences, we propose that future research should assess which subset of children does benefit from mass deworming, if any, using individual patient data meta‐analysis. This analysis and other work could focus on whether it is feasible to develop a case‐finding tool with clinical data that could identify children and settings that would benefit from treatment. Plain Language Summary Mass deworming programmes have little or no effect on most welfare outcomes. The Campbell review in brief The effectiveness and cost‐effectiveness of mass deworming of children to improve child health and other outcomes is debated. This independent analysis reinforces the case against mass deworming, finding little or no effect on most welfare outcomes. What is this review about? Soil‐transmitted helminthiasis and schistosomiasis affect more than a third of the world's population. There is debate about the effectiveness and cost‐effectiveness of mass deworming of children to improve child health and other outcomes in endemic areas. This review evaluates the effects of mass deworming for soil‐transmitted helminths on growth, educational achievement, cognition, school attendance, quality of life and adverse effects in children in endemic helminth areas. What studies were included? Included studies examine out mass deworming for soil‐transmitted helminths (alone or in combination with other drugs or child health interventions) for children aged 6 months to 16 years, and report at least one of the following outcomes: growth, school attendance, school performance, cognitive processing or development, well‐being, or adverse events. Included study designs are randomized trials, interrupted time series and non‐experimental studies that used statistical methods of analysis to match participants with non‐participants, or statistical methods to account for confounding and sample selection bias. Sixty‐five studies are analyzed in the review, with a treatment duration from 4 months to 5 years, covering 1,092,120 children, including five long‐term studies 8‐10 years after mass deworming programs with over 90,000 children. These studies were conducted in 23 low and middle income countries. Most programmes studied conduct deworming twice per year or more frequently, with only two studies of programmes deworming just once per year. Does deworming improve child health and other welfare outcomes? Mass deworming for soil‐transmitted helminths probably has little to no effect on weight, height, school attendance, cognition measured by short‐term attention, or mortality. There are no data on short‐term quality of life and little evidence of adverse effects. Mass deworming for schistosomiasis alone may slightly increase weight but probably has little to no effect on height and cognition. The evidence does not support indirect benefits for untreated children from being exposed to treated children. One moderate quality long term study showed an increase in economic productivity (hours worked) and increase in educational enrollment 10 years later of mass deworming and hygiene promotion. But, it is uncertain whether these effects are due to the deworming or the combined hygiene intervention. Findings are consistent for various groups of the population by age, gender, worm prevalence, baseline nutritional status, compliance, impact on worms, infection intensity, types of worms, risk of bias, and study characteristics. Deworming for children who screened positive for schistosomiasis or soil‐transmitted helminths results in larger gains in weight but no difference in effect on height, cognition or school attendance. Also, one low to moderate quality study showed long‐term benefit on school enrolment of sanitation improvement combined with screening and treating people for hookworm infection. What are the implications of this review for policy makers and decision makers? This independent analysis reinforces the case against mass deworming. In addition to a reconsideration of mass deworming programs in their current form, additional policy options need to be explored to improve child health and nutrition in worm‐endemic areas. For schistosomiasis, policy implications are that mass deworming may be effective at improving weight. What are the research implications of this review? Future research should assess which subset of children benefit from mass deworming using individual‐level meta‐analysis. This analysis could explore whether it is feasible to develop a case‐finding tool to identify children and settings which will benefit from treatment.