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Authors:
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Danny A Milner, Jr, Jimmy Vareta, Clarissa Valim, Jacqui Montgomery, Rachel F Daniels, Sarah K Volkman, Daniel E Neafsey, Daniel J Park, Stephen F Schaffner, Nira C Mahesh, Kayla G Barnes, David M Rosen, Amanda K Lukens, Daria Van-Tyne, Roger C Wiegand, Pardis C Sabeti, Karl B Seydel, Simon J Glover, Steve Kamiza, Malcolm E Molyneux, Terrie E Taylor, Dyann F Wirth
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Abstract:
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Background
Cerebral malaria, a severe form of Plasmodium falciparuminfection, is an important cause of mortality in sub-Saharan African children. A Taqman 24 Single Nucleotide Polymorphisms (SNP) molecular barcode assay was developed for use in laboratory parasites which estimates genotype number and identifies the predominant genotype.
Methods
The 24 SNP assay was used to determine predominant genotypes in blood and tissues from autopsy and clinical patients with cerebral malaria.
Results
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.
Conclusions
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.
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