PMC

Incidence of malaria hospitalisations and deaths from malaria (a) and clinical malaria (b) according to time since the most recent SMC course. Incidence rates are presented per 1,000 person-years at risk. Vertical bars show 95% CIs. ‘No SMC this year’ indicates children who had not yet received their first course of SMC in that year of the study (but who subsequently received SMC). Malaria hospitalisations and deaths from malaria were defined as hospital admission with a diagnosis of malaria and blood-slide–or RDT-confirmed P. falciparum infection or deaths for which malaria was listed as the primary diagnosis. Clinical malaria was defined as attendance at study health facility with a history of fever or measured temperature ≥37.5 °C, with malaria infection confirmed by RDT. CI, confidence interval; RDT, rapid diagnostic test; SMC, seasonal malaria chemoprevention.

There are three potential pathogenetic routes to WHO-defined cerebral malaria (CM). The first, shown in red, is the classical pathway: a malaria infection evolves into retinopathy-positive (Ret+) CM. The second and third possibilities produce retinopathy-negative (Ret-) CM. In (a) the coma is entirely the result of another etiology and the malaria parasitemia is incidental. In (b), the coma is a product of the interaction between the malaria parasitemia and an additional cause (or causes) of coma. Sickle cell trait is underrepresented in patients with Ret+ and Ret- cerebral malaria (CM) because of the bottleneck at the transition between 'malaria infection' (asymptomatic malaria) and 'malaria disease' (uncomplicated malaria). Blood group O is underrepresented in patients with Ret+ CM, but not in those with Ret- CM. Taken together, the results for sickle cell trait and blood group O suggest that some Ret- CM cases occur through pathway (b) (because sickle cell trait is underrepresented in Ret- CM) and that malaria parasites contribute to the pathogenesis of these cases, and that sickle cell trait reduces the pathogenetic potential of malaria infection for Ret- CM but do not provide evidence that blood group O reduces the pathogenetic potential of malaria infection for Ret- CM.
DOI: http://dx.doi.org/10.7554/eLife.23699.004

CHEMAL, Chemotherapy of malaria; FIELDMAL, Epidemiology of malaria; IMMAL, Immunology of malaria; NETs, bednets; ACTs, artemisinin combination therapy; SM, severe malaria; HMM, home management of malaria.

Incidence of malaria hospitalisations and deaths from malaria (left panel) and uncomplicated clinical malaria (right panel) by age group over the study period. Malaria hospitalisations and deaths from malaria were defined as hospital admission with a diagnosis of malaria and blood-slide–or RDT-confirmed P. falciparum infection or deaths for which malaria was listed as the primary diagnosis. Clinical malaria was defined as attendance at study health facility with a history of fever or measured temperature ≥37.5 °C, with malaria infection confirmed by RDT. Incidence rates are presented per 1,000 person-years and include repeat events in the same child, provided the healthcare contact occurred more than 7 days apart. Vertical bars show 95% CIs. CI, confidence interval; RDT, rapid diagnostic test.