Related Experiment Video
Updated: Mar 22, 2026
In Vivo Tracking of Edema Development and Microvascular Pathology in a Model of Experimental Cerebral Malaria Using Magnetic Resonance Imaging
Published on: June 8, 2017
Malaria illness mediated by anaemia lessens cognitive development in younger Ugandan children
Michael J Boivin1, Alla Sikorskii2, Itziar Familiar-Lopez3
1Department of Psychiatry, Michigan State University, 965 Fee Road, Room A227, East Fee Hall, East Lansing, MI, 48824, USA. boivin@msu.edu.
Insights
Preventing malaria and anemia in young children in Africa is crucial for cognitive development. HIV exposure also negatively impacts neurodevelopment, highlighting the need for comprehensive interventions.
Area of Science:
- Global Health
- Pediatric Neurodevelopment
- Infectious Disease Epidemiology
Background:
- Asymptomatic Plasmodium falciparum malaria negatively impacts cognitive function in schoolchildren.
- Intermittent preventive treatment for malaria improves cognitive outcomes.
- The impact of early childhood chemoprevention on neurodevelopment remains unknown.
Purpose of the Study:
- To evaluate early child development as a primary outcome in a randomized clinical trial of antimalarial chemoprevention.
- To assess the benefits of different antimalarial chemoprevention strategies in infancy.
- To investigate the influence of malaria, anemia, and HIV exposure on neurodevelopment.
Main Methods:
- An open-label, randomized trial involving infants aged 4-6 months to 24 months in Uganda.
- Four treatment arms: no chemoprevention, daily trimethoprim-sulfamethoxazole, monthly sulfadoxine-pyrimethamine, or monthly dihydroartemisinin-piperaquine (DP).
- Neurodevelopment assessed using the Mullen Scales of Early Learning (MSEL) at 2 and 3 years; malaria and anemia also monitored. Participants were HIV-unexposed uninfected (HUU) or HIV-exposed uninfected (HEU).
Main Results:
- Dihydroartemisinin-piperaquine (DP) demonstrated high efficacy against malaria and anemia.
- No significant difference in MSEL outcomes was observed between treatment arms.
- Malaria episodes negatively predicted cognitive performance (MSEL) at 2 and 3 years, mediated by anemia.
- HIV-exposed uninfected (HEU) children performed significantly poorer on receptive language development compared to HUU children, irrespective of malaria and anemia.
Conclusions:
- Malaria with anemia and HIV exposure are significant risk factors for impaired early childhood neurodevelopment in malaria-endemic regions.
- Effective and cost-efficient interventions are essential for malaria prevention in very young children.
- Targeted strategies addressing malaria, anemia, and HIV exposure are needed to improve neurodevelopmental outcomes.
Background:
Asymptomatic 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.
Methods:
Infants 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).
Results:
DP 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).
Conclusions:
Malaria 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.
