Mass deworming for improving health and cognition of children in endemic helminth areas: A systematic review and individual participant data network meta‐analysis

BackgroundSoil transmitted (or intestinal) helminths and schistosomes affect millions of children worldwide.ObjectivesTo use individual participant data network meta‐analysis (NMA) to explore the effects of different types and frequency of deworming drugs on anaemia, cognition and growth across potential effect modifiers.Search MethodsWe developed a search strategy with an information scientist to search 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 March 27, 2018. We also searched grey literature, websites, contacted authors and screened references of relevant systematic reviews.Selection CriteriaWe included randomised and quasirandomised deworming trials in children for deworming compared to placebo or other interventions with data on baseline infection.Data Collection and AnalysisWe conducted NMA with individual participant data (IPD), using a frequentist approach for random‐effects NMA. The covariates were: age, sex, weight, height, haemoglobin and infection intensity. The effect estimate chosen was the mean difference for the continuous outcome of interest.ResultsWe received data from 19 randomized controlled trials with 31,945 participants. Overall risk of bias was low. There were no statistically significant subgroup effects across any of the potential effect modifiers. However, analyses showed that there may be greater effects on weight for moderate to heavily infected children (very low certainty evidence).Authors' ConclusionsThis analysis reinforces the case against mass deworming at a population‐level, finding little effect on nutritional status or cognition. However, children with heavier intensity infections may benefit more. We urge the global community to adopt calls to make data available in open repositories to facilitate IPD analyses such as this, which aim to assess effects for the most vulnerable individuals.</div

Countries without previous rounds of MDA for LF.

<p>*Treatment durations for <i>Culex</i> spp. were used for countries in which primary vector species was unknown.</p><p>^<b>α</b>Treatment assumed to occur once annually using diethylcarbamazine citrate (DEC) and albendazole (ALB), or in areas co-endemic with onchocerciasis, ivermectin (IVM) and albendazole (ALB)</p><p>^<b>¤</b> Preventive Chemotherapy Databank Lymphatic Filariasis [Internet]. WHO. 2015 [cited 2015 January 20]. Available from: <a href="http://www.who.int/neglected_diseases/preventive_chemotherapy/lf/en/" target="_blank">http://www.who.int/neglected_diseases/preventive_chemotherapy/lf/en/</a>.</p><p>^<b>¥</b> United Nations, Department of Economic and Social Affairs, Population Division (2013). World Population Prospects: The 2012 Revision, Key Findings and Advance Tables. Working Paper No. ESA/P/WP.227.</p><p>^± Refers to MDA schedules assumed to be used by these countries for the purposes of our analysis for the global elimination scenario, eradication I, eradication II, and eradication III scenarios, respectively. In schedule I, two deciles (20%) of the at-risk population are added to the MDA schedule annually. In schedule II, one decile is added annually. In schedule III, one decile is added every 2 years, and in schedule IV, one decile is added every 3rd year (see: Rate of Scale-Up and History of Control). ‘-‘ refers to a continued absence of an MDA program. ‘0’ refers to instantaneous scale-up.</p><p>^§A 4-year delay was assumed for countries that have not completed LF mapping, while a 1-year delay was assumed for those that have completed mapping but have not previously carried out MDA.</p><p>Countries without previous rounds of MDA for LF.</p

Projected treatment needs (in millions) by WHO region with 95% credible intervals.

<p>Projected treatment needs (in millions) by WHO region with 95% credible intervals.</p

Cumulative number of treatments by year.

<p>The line with circular markers represents the global elimination (comparator) scenario. As highlighted in the text boxes, both the global elimination and eradication I scenario are estimated to conclude MDA after 37 years of MDA. Eradication II, the intensified scale-up scenario, sees the last round of MDA to occur by 2032, after 19 years of MDA. Eradication III is estimated to require 15 years of MDA, concluding in 2028.</p

Incremental treatment projections by year (global elimination scenario as comparator).

<p>All eradication scenarios see an increase in the number of treatments after 4 years as the result of the imposed delay for countries that have not previously finished mapping or begun MDA. By 2024, the eradication III scenario requires less treatments than the global elimination (comparator) scenario, and from 2028, the eradication II scenario is also projected to require fewer treatments than global elimination.</p

Estimates of the number of annual MDA rounds needed to reach local LF elimination by transmission archetypes, based on sets of 500 simulations using EpiFil and assuming 85% coverage.

<p>^<b>α</b>Treatment assumed to occur once annually using diethylcarbamazine citrate (DEC) and albendazole (ALB), or in areas co-endemic with onchocerciasis, ivermectin (IVM) and albendazole (ALB)</p><p>Estimates of the number of annual MDA rounds needed to reach local LF elimination by transmission archetypes, based on sets of 500 simulations using EpiFil and assuming 85% coverage.</p

Key features of the proposed scenarios for global elimination and eradication of LF.

<p>^¥Assuming country requires MDA</p><p>Key features of the proposed scenarios for global elimination and eradication of LF.</p

Dose responses for eggs recovered from 4 individual study subjects.

<p>Parts <b>A–D</b> show data from individual subjects (ID numbers shown above each graph) either uncorrected (□, dotted lines), or corrected (•, solid lines) for embryonation. Each data point represents mean ± SE, n = 2.</p

Countries that previously carried out MDA for LF.

<p>*Treatment durations for <i>Culex</i> spp. were used for countries in which primary vector species was unknown.</p><p>^<b>α</b>Treatment assumed to occur once annually using diethylcarbamazine citrate (DEC) and albendazole (ALB), or in areas co-endemic with onchocerciasis, ivermectin (IVM) and albendazole (ALB)</p><p>^<b>¤</b> Preventive Chemotherapy Databank Lymphatic Filariasis [Internet]. WHO. 2015 [cited 2015 January 20]. Available from: <a href="http://www.who.int/neglected_diseases/preventive_chemotherapy/lf/en/" target="_blank">http://www.who.int/neglected_diseases/preventive_chemotherapy/lf/en/</a>.</p><p>^<b>¥</b> United Nations, Department of Economic and Social Affairs, Population Division (2013). World Population Prospects: The 2012 Revision, Key Findings and Advance Tables. Working Paper No. ESA/P/WP.227.</p><p>^± Refers to MDA schedules assumed to be used by these countries for the purposes of our analysis for the global elimination scenario, eradication I, eradication II, and eradication III scenarios, respectively. In schedule I, two deciles (20%) of the at-risk population are added to the MDA schedule annually. In schedule II, one decile is added annually. In schedule III, one decile is added every 2 years, and in schedule IV, one decile is added every 3rd year (see: Rate of Scale-Up and History of Control). ‘0’ refers to instantaneous scale-up.</p><p>Countries that previously carried out MDA for LF.</p

Maps depicting the final year of MDA per country for the four scenarios.

<p>The global elimination scenario does not include countries that have not yet begun MDA.</p