Abstract
BackgroundThe host response to infection by Plasmodium falciparum, the parasite most often responsible for severe malaria, ranges from asymptomatic parasitaemia to death. The clinical trajectory of malaria is influenced by host genetics and parasite load, but the factors determining why some infections produce uncomplicated malaria and some proceed to severe disease remain incompletely understood.MethodsTo identify molecular markers of severe falciparum malaria, human gene expression patterns were compared between children aged 6 months to 5 years with severe and uncomplicated malaria who were enrolled in a case–control study in Bandiagara, Mali. Microarrays were used to obtain expression data on severe cases and uncomplicated controls at the time of acute disease presentation (five uncomplicated and five severe), 1 week after presentation (three uncomplicated and three severe) and treatment initiation, and in the subsequent dry season (late convalescence, four uncomplicated and four severe). This is a pilot study for the first use of microarray technology in Mali.ResultsComplement and toll-like receptor (TLR) pathways were differentially expressed, with severe cases showing higher expression of the C1q, TLR2, TLR4, TLR8, and CR1 genes. Other genes previously associated with malaria pathogenesis, GZMB, FOS and HSPA6, were also higher among severe cases. TLR2, TLR4, TLR8, CR1, GZMB, FOS, and HSPA6 genes were expressed at lower levels in severe cases at late convalescence.ConclusionsOverexpression of genes previously associated with uncomplicated malaria was associated with severe disease. Low baseline expression of these genes may represent candidate markers for severe malaria. Despite the small sample size, results of this pilot study offer promising targets for follow-up analyses.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1189-6) contains supplementary material, which is available to authorized users.
Highlights
The host response to infection by Plasmodium falciparum, the parasite most often responsible for severe malaria, ranges from asymptomatic parasitaemia to death
Five severe cases with cerebral symptoms and five uncomplicated malaria controls were chosen for pilot microarray studies of gene expression on the day of presentation at the clinic
This study suggests that overexpression of genes previously associated with uncomplicated malaria may be associated with severe disease
Summary
The host response to infection by Plasmodium falciparum, the parasite most often responsible for severe malaria, ranges from asymptomatic parasitaemia to death. The clinical trajectory of malaria is influenced by host genetics and parasite load, but the factors determining why some infections produce uncomplicated malaria and some proceed to severe disease remain incompletely understood. The response to infection by Plasmodium falciparum, the parasite responsible for most severe malaria, is varied and complex, ranging from asymptomatic parasitaemia to death. Numerous factors affect the clinical manifestation of malaria, including a patient’s age [3], level of P. falciparum transmission [4], parasite virulence [5], and gene expression levels in both the host and the parasite [6, 7], among others [8]. The biological bases for differences in clinical manifestations remain largely unexplained
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