Human cerebral malaria and Plasmodium falciparum genotypes in Malawi

The 24 SNP assay was used to determine predominant genotypes in blood and tissues from autopsy and clinical patients with cerebral malaria.Single genotypes were shared between the peripheral blood, the brain, and other tissues of cerebral malaria patients, while malaria-infected patients who died of non-malarial causes had mixed genetic signatures in tissues examined. Children with retinopathy-positive cerebral malaria had significantly less complex infections than those without retinopathy (OR = 3.7, 95% CI [1.51-9.10]).The complexity of infections significantly decreased over the malaria season in retinopathy-positive patients compared to retinopathy-negative patients.Cerebral malaria patients harbour a single or small set of predominant parasites; patients with incidental parasitaemia sustain infections involving diverse genotypes. Limited diversity in the peripheral blood of cerebral malaria patients and correlation with tissues supports peripheral blood samples as appropriate for genome-wide association studies of parasite determinants of pathogenicity.The global Plasmodium falciparum parasite population is highly diverse, especially in antigens transported to the erythrocyte surface where they can interact with the human immune system [1,2]. The major question being addressed, "Are there parasite genetic determinants of cerebral malaria and can we identify them?" requires careful step-wise considerations. Background multiplicity of Plasmodium falciparum infection in both asymptomatic and symptomatic individuals is high in Malawi due to intense transmission. Several sequencing approaches using material directly from tissue or peripheral blood have been useful for SNP discovery at the population level. Understanding sequencing data from mixed infections however has been difficult to interpret and quantify for an individual parasite genotype within a single patient. Previously, attempts to evaluate individual var gene transcripts from patients by sequencing showe