Distinct transcriptomic signatures define febrile malaria depending on initial infective states, asymptomatic or uninfected

Cumulative malaria parasite exposure in endemic regions often results in the acquisition of partial immunity and asymptomatic infections. However, there is limited information on how host-parasite interactions mediate maintenance of chronic symptomless infections that sustain malaria transmission. In this study, we identified uninfected and asymptomatic individuals and followed them until they manifested with symptoms of fever in the presence of malaria parasites and compared the gene expression profiles of peripheral blood mononuclear cells (PBMCs). The host response of asymptomatic children was characterized by downregulation of genes associated with inflammatory responses, compared to uninfected children and children with febrile malaria. They did show greater expression of some genes associated with the humoral response compared to uninfected children. Interestingly, the host responses during febrile infections that followed an asymptomatic infection featured stronger inflammatory responses, whereas the febrile host responses from previously uninfected children featured increased humoral immune responses. Overall design: Peripheral blood monocytes were taken from a longitudinal cohort of individuals in a malaria endemic region to examine the immune response to infection. In the earliest sample, individuals were classed as either asymptomatically infected with malaria or uninfected. Individuals then received monitoring until they developed a febrile infection, whereupon a second sample was taken. Both paired samples (before and during febrile infection) and single samples from individuals seen in just one of the three states (asymptomatic, uninfected, febrile) are included here.