Severe Malaria Pathogenesis and Neurodevelopmental Impairment after Malaria


Professor Chandy John’s lab group has demonstrated in prospective studies that cerebral malaria (CM) in children is associated with developmental, behavioral and mental health impairment. In addition, severe malarial anemia (SMA), which affects more children than CM, and has no neurologic manifestations, has been shown to be associated with neurodevelopmental and behavioral impairment. New preliminary data also suggests that malaria with repeated seizures is also associated with subsequent impairment in attention. The John Lab has demonstrated that these effects can remain as long as 2 years after the severe malaria episode.


In a study that completed follow-up in 2018, neurodevelopmental and behavioral outcomes were evaluated in children with five types of severe malaria (CM, SMA, malaria with repeated seizures, respiratory distress and prostration). The children with severe malaria were recruited from; 1) the Paediatric Acute Care Unit (ACU) at Mulago National Referral and Teaching Hospital, Kampala, Uganda; 2) the Pediatric Emergency ward at Jinja Regional Referral District Hospital, Jinja, Uganda.

The goal of the studies in Uganda included determining the factors impacting the:

  1. Pathogenesis of severe malaria
  2. Neurodevelopmental impairment (NDI) following severe malaria, in children with the five types of severe malaria treated with artesunate.

Results from this study provided new knowledge about neurodevelopmental impairment (NDI) in malaria and the mechanisms through which this occurs in each of the five types of severe malaria. Equipped with this new knowledge, the project intends to develop interventions to prevent NDI in the millions of children annually who become ill with severe malaria. The risk factors to be assessed are all potentially amenable to currently available medications or nutrients and it is therefore expected that the study conclusions will provide evidence to support clinical trials of adjunctive therapy in severe malaria specifically to prevent NDI.