Malaria illness mediated by anaemia lessens cognitive development in younger Ugandan children.

Michael J Boivin,Moses Kamya,Noeline Nakasujja,Itziar Familiar-Lopez,Judy K Bass,Victor Bigira,James Kapisi,Horacio Ruiseñor-Escudero,Grant Dorsey,Robert O Opoka,Mary Muhindo,Alla Sikorskii

doi:10.1186/s12936-016-1266-x

Abstract

BackgroundAsymptomatic falciparum malaria is associated with poorer cognitive performance in African schoolchildren and intermittent preventive treatment of malaria improves cognitive outcomes. However, the developmental benefits of chemoprevention in early childhood are unknown. Early child development was evaluated as a major outcome in an open-label, randomized, clinical trial of anti-malarial chemoprevention in an area of intense, year-round transmission in Uganda.MethodsInfants were randomized to one of four treatment arms: no chemoprevention, daily trimethoprim–sulfamethoxazole, monthly sulfadoxine–pyrimethamine, or monthly dihydroartemisinin–piperaquine (DP), to be given between enrollment (4–6 mos) and 24 months of age. Number of malaria episodes, anaemia (Hb < 10) and neurodevelopment [Mullen Scales of Early Learning (MSEL)] were assessed at 2 years (N = 469) and at 3 years of age (N = 453); at enrollment 70 % were HIV-unexposed uninfected (HUU) and 30 % were HIV-exposed uninfected (HEU).ResultsDP was highly protective against malaria and anaemia, although trial arm was not associated with MSEL outcomes. Across all treatment arms, episodes of malarial illness were negatively predictive of MSEL cognitive performance both at 2 and 3 years of age (P = 0.02). This relationship was mediated by episodes of anaemia. This regression model was stronger for the HEU than for the HUU cohort. Compared to HUU, HEU was significantly poorer on MSEL receptive language development irrespective of malaria and anaemia (P = 0.01).ConclusionsMalaria with anaemia and HIV exposure are significant risk factors for poor early childhood neurodevelopment in malaria-endemic areas in rural Africa. Because of this, comprehensive and cost/effective intervention is needed for malaria prevention in very young children in these settings.

Highlights

Asymptomatic falciparum malaria is associated with poorer cognitive performance in African school‐ children and intermittent preventive treatment of malaria improves cognitive outcomes
Intermittent prevention treatment (IPT) for malaria in schools and in communities has had cognitive and academic benefits in rural Gambia [8], western Kenya [9], Mali [10], and Zambia [11, 12], one negative outcome was reported in a Kenyan study [13]
Study site This observational study of neurodevelopmental outcomes was embedded within a malaria chemoprevention randomized controlled trial (RCT) study conducted at the Tororo District Hospital near the Kenyan border in eastern Uganda [14, 15] (ClinicalTrials.gov number NCT00948896)

Summary

Introduction

Asymptomatic falciparum malaria is associated with poorer cognitive performance in African school‐ children and intermittent preventive treatment of malaria improves cognitive outcomes. Intermittent prevention treatment (IPT) for malaria in schools and in communities has had cognitive and academic benefits in rural Gambia [8], western Kenya [9], Mali [10], and Zambia [11, 12], one negative outcome was reported in a Kenyan study [13]. All these IPT clinical trials involved school-age children randomized by classrooms, schools or villages.

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