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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 pro

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 pro

Background: The home environment is reported to contribute significantly to children's developing cognitive skills. However, it is not yet evident whether this role prevails in the context of extreme poverty and frequent ill-health. We therefore investigated the role of the home environment in Ugandan children taking into account the frequent infections and extreme poverty in which they lived. Methods: Cognitive abilities of 163 5-year-old children were assessed. Home environments of these children, their health status and family socioeconomic status (SES) were assessed respectively using the EC-HOME, anthropometry and illnesses, and traditional SES measures. Structural equation analyses compared five models on the influence of the home environment, SES, and child health on the cognitive scores. Results: The model in which the home environment mediates the combined influence of SES and child health on cognitive performance showed a particularly good fit to the data compared with the four alternative models, i.e. those in which the HOME, SES and health independently influence cognitive performance. Conclusions: Home environments providing cognitive stimulation can enable children to overcome effects of major adverse life experiences on cognitive development.

Background. Helminth and malaria coinfections are common in the tropics. We investigated the hypothesis that prenatal exposure to these parasites might influence susceptibility to infections such as malaria in childhood.Methods. In a birth cohort of 2,345 mother-child pairs in Uganda, maternal helminth and malaria infection status was determined during pregnancy, and childhood malaria episodes recorded from birth to age five years. We examined associations between maternal infections and malaria in the offspring.Results. Common maternal infections were hookworm (45%), Mansonella perstans (21%), Schistosoma mansoni (18%), and Plasmodium falciparum (11%). At age 5 years, 69% of the children were still under follow-up. The incidence of malaria was 34 episodes per 100 child-years, and the mean prevalence of asymptomatic malaria at annual visits was 5.4%. Maternal hookworm and M. perstans infections were associated with an increased rate of childhood clinical malaria (adjusted hazard ratio [aHR], 1.24 [95% confidence interval (CI), 1.10-1.41] and 1.20 [95% CI, 1.05-1.38], respectively). S. mansoni infection had no consistent association with childhood malaria.Conclusion. This is the first report of an association between helminth infections in pregnancy and malaria in the offspring, and indicates that helminth infections in pregnancy may increase the burden of childhood malaria morbidity.

Background. Helminth and malaria coinfections are common in the tropics. We investigated the hypothesis that prenatal exposure to these parasites might influence susceptibility to infections such as malaria in childhood.Methods. In a birth cohort of 2,345 mother-child pairs in Uganda, maternal helminth and malaria infection status was determined during pregnancy, and childhood malaria episodes recorded from birth to age five years. We examined associations between maternal infections and malaria in the offspring.Results. Common maternal infections were hookworm (45%), Mansonella perstans (21%), Schistosoma mansoni (18%), and Plasmodium falciparum (11%). At age 5 years, 69% of the children were still under follow-up. The incidence of malaria was 34 episodes per 100 child-years, and the mean prevalence of asymptomatic malaria at annual visits was 5.4%. Maternal hookworm and M. perstans infections were associated with an increased rate of childhood clinical malaria (adjusted hazard ratio [aHR], 1.24 [95% confidence interval (CI), 1.10-1.41] and 1.20 [95% CI, 1.05-1.38], respectively). S. mansoni infection had no consistent association with childhood malaria.Conclusion. This is the first report of an association between helminth infections in pregnancy and malaria in the offspring, and indicates that helminth infections in pregnancy may increase the burden of childhood malaria morbidity.

We tested the hypothesis that maternal worm infections in pregnancy affect infant motor and neurocognitive development, and that anthelminthic treatment during pregnancy can reverse these effects. We used measures which examine infant motor, cognitive and executive function, including inhibition. We assessed 983 Ugandan infants aged 15 months, using locally appropriate measures within the Entebbe Mother and Baby Study, a trial of anthelminthic treatment during pregnancy. Key exposures were maternal worm infections and anthelminthic treatment during pregnancy. Effects of other health and social factors were controlled for statistically. Of the five major worm species found in the pregnant women, two had influences on the developmental measures: Maternal Mansonella perstans and Strongyloides stercoralis infections showed negative associations with the A-not B-task, and Language, respectively. Performance on other psychomotor and cognitive measures was associated with illnesses during infancy and infants' behavior during assessment, but not with maternal worm infections. There were no positive effects of maternal anthelminthic treatment on infant abilities. Mansonella perstans and Strongyloides stercoralis infection during pregnancy seem associated with impaired early executive function and language, respectively, but single-dose anthelminthic treatment during pregnancy was not beneficial. The biological mechanisms that could underlie these neurocognitive effects are discussed. (JINS, 2012, 18, 1019-1030).

Helminth infections may modulate immune responses to unrelated pathogens and allergens; these effects may commence prenatally. We addressed the hypothesis that anthelminthic treatment in pregnancy and early childhood would improve responses to immunisation and modulate disease incidence in early childhood with both beneficial and detrimental effects.A randomised, double-blind, placebo-controlled trial was conducted in Entebbe, Uganda [ISRCTN32849447]. In three independent randomisations, 2507 pregnant women were allocated to receive single-dose albendazole or placebo, and praziquantel or placebo; 2016 of their offspring were randomised to receive quarterly single-dose albendazole or placebo from age 15 months to 5 years. Primary outcomes were post-immunisation recall responses to BCG and tetanus antigens, and incidence of malaria, diarrhoea, and pneumonia; incidence of eczema was an important secondary outcome. Analysis was by intention-to-treat. Of 2345 live births, 1622 (69%) children remained in follow-up at age 5 years. 68% of mothers at enrolment, and 11% of five-year-olds, had helminth infections. Maternal hookworm and Schistosoma mansoni were effectively treated by albendazole and praziquantel, respectively; and childhood hookworm and Ascaris by quarterly albendazole. Incidence rates of malaria, diarrhoea, pneumonia, and eczema were 34, 65, 10 and 5 per 100 py, respectively. Albendazole during pregnancy caused an increased rate of eczema in the children (HR 1.58 (95% CI 1.15–2.17), p = 0.005). Quarterly albendazole during childhood was associated with reduced incidence of clinical malaria (HR 0.85 (95% CI 0.73–0.98), p = 0.03). There were no consistent effects of the interventions on any other outcome.Routine use of albendazole in pregnancy may not always be beneficial, even in tropical developing countries. By contrast, regular albendazole treatment in preschool children may have an additional benefit for malaria control where helminths and malar

Helminth infections may modulate immune responses to unrelated pathogens and allergens; these effects may commence prenatally. We addressed the hypothesis that anthelminthic treatment in pregnancy and early childhood would improve responses to immunisation and modulate disease incidence in early childhood with both beneficial and detrimental effects.A randomised, double-blind, placebo-controlled trial was conducted in Entebbe, Uganda [ISRCTN32849447]. In three independent randomisations, 2507 pregnant women were allocated to receive single-dose albendazole or placebo, and praziquantel or placebo; 2016 of their offspring were randomised to receive quarterly single-dose albendazole or placebo from age 15 months to 5 years. Primary outcomes were post-immunisation recall responses to BCG and tetanus antigens, and incidence of malaria, diarrhoea, and pneumonia; incidence of eczema was an important secondary outcome. Analysis was by intention-to-treat. Of 2345 live births, 1622 (69%) children remained in follow-up at age 5 years. 68% of mothers at enrolment, and 11% of five-year-olds, had helminth infections. Maternal hookworm and Schistosoma mansoni were effectively treated by albendazole and praziquantel, respectively; and childhood hookworm and Ascaris by quarterly albendazole. Incidence rates of malaria, diarrhoea, pneumonia, and eczema were 34, 65, 10 and 5 per 100 py, respectively. Albendazole during pregnancy caused an increased rate of eczema in the children (HR 1.58 (95% CI 1.15–2.17), p = 0.005). Quarterly albendazole during childhood was associated with reduced incidence of clinical malaria (HR 0.85 (95% CI 0.73–0.98), p = 0.03). There were no consistent effects of the interventions on any other outcome.Routine use of albendazole in pregnancy may not always be beneficial, even in tropical developing countries. By contrast, regular albendazole treatment in preschool children may have an additional benefit for malaria control where helminths and malar