Effect of intensive versus standard anthelminthic treatment on growth and cognition among children living in a high Schistosoma mansoni transmission setting: a study nested within a cluster-randomised trial

Abstract

Background: Schistosomiasis and other worm infections have been associated with growth and cognitive impairments; however, whether treatment reverses these effects is uncertain. Moreover, mechanisms linking these infections to cognition are not clear. We aimed to compare growth and cognitive benefits of intensive versus standard anthelminthic treatment in school-aged-children and explore processes that might be involved. We hypothesised that intensive treatment would have greater benefits than standard treatment. Methods: The study was nested within a cluster-randomised trial of either quarterly single-dose praziquantel of 40mg/kg to treat Schistosoma mansoni plus triple dose albendazole of 400mg (intensive treatment) to treat soil-transmitted worms including Ascaris lumbricoides, hookworm and Trichuris trichiura, or annual single-dose praziquantel 40mg/kg plus six-monthly single-dose albendazole 400mg (standard treatment) conducted in the Koome islands in Lake Victoria, Uganda (ISRCTN47196031). Children aged 5-9 years (N=384) were assessed on primary outcomes (height, weight and eight measures of cognitive ability), worm infection, and proposed mediators of worm effects (cytokines, iron status, physical activity) at one year (intensive n=85; standard n=64) and at two years (intensive n=158; standard n=128) of the intervention. Linear regression was used to examine intervention effects on height, weight and cognitive performance. Linear mixed effects models were used to study changes in growth and cognitive performance between the two arms across the two time-points. Results: Intensive treatment resulted in lower Schistosoma mansoni prevalence than standard treatment (at one year, 41% versus 70%; adjusted odds ratio (aOR)=0.24, 95% CI: 0.12, 0.49; at two years, 39% versus 69%; aOR=0.27; 95% CI: 0.16, 0.43) but there were no significant differences in growth and cognitive outcomes at either time-point. Worms and treatment showed no consistent association with the proposed mediators of worm effects. Conclusion: Reduction in worm burden may not improve growth and cognitive outcomes in high S. mansoni transmission settings. Possible implications are discussed.