New perspectives on the likely mechanisms of severe malaria

By David Conway

Gene expression patterns in humans and malaria parasites give new perspectives on the likely pathogenic mechanisms of severe malaria.

By using human and parasite dual RNA-sequencing, the research provides insight into interactions associated with severity of infection.

Most studies of infectious disease pathogenesis focus on either host or pathogen, despite the fact that clinical outcome is determined by their interaction. Dual RNA-sequencing has been developed as a method for transcriptomic assessment of such interactions. Here we performed dual transcriptome analyses on samples from malaria-infected Gambian children to reveal mechanisms driving the systemic pathophysiology of severe malaria.

We report hundreds of human and parasite genes differentially expressed between severe and uncomplicated malaria, with distinct profiles associated with coma, hyperlactatemia, and thrombocytopenia. These findings provide a framework for understanding the contributions of host and parasite to the pathogenesis of severe malaria and identifying targets for adjunctive therapy.

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