Host immune response in returning travellers infected with malaria

Clinical observations suggest that Canadian-born (CB) travellers are prone to more severe malaria, characterized by higher parasite density in the blood, and severe symptoms, such as cerebral malaria and renal failure, than foreign-born travellers (FB) from areas of malaria endemicity. It was hypothesized that host cytokine and chemokine responses differ significantly in CB versus FB patients returning with malaria, contributing to the courses of severity. A more detailed understanding of the profiles of cytokines, chemokines, and endothelial activation may be useful in developing biomarkers and novel therapeutic approaches for malaria.

The patient population for the study (n = 186) was comprised of travellers returning to Toronto, Canada between 2007 and 2011. The patient blood samples' cytokine, chemokine and angiopoietin concentrations were determined using cytokine multiplex assays, and ELISA assays.

Significantly higher plasma cytokine levels of IL-12 (p40) were observed in CB compared to FB travellers, while epidermal growth factor (EGF) was observed to be higher in FB than CB travellers. Older travellers (55 years old or greater) with Plasmodium vivax infections had significantly higher mean cytokine levels for IL-6 and macrophage colony-stimulating factor (M-CSF) than other adults with P. vivax (ages 18-55). Patients with P. vivax infections had significantly higher mean cytokine levels for monocyte chemotactic protein-1 (MCP-1), and M-CSF than patients with Plasmodium falciparum. Angiopoietin 2 (Ang-2) was higher for patients infected with P. falciparum than P. vivax, especially when comparing just the FB groups. IL-12 (p40) was higher in FB patients with P. vivax compared to P. falciparum. Il-12 (p40) was also higher in patients infected with P. vivax than those infected with Plasmodium ovale. For patients travelling to West Africa, IFN-γ and IL-6 was lower than for patients who were in other regions of Africa.

Significantly higher levels of IL-12 (p40) and lower levels of EGF in CB travellers may serve as useful prognostic markers of disease severity and help guide clinical management upon return. IL-6 and M-CSF in older adults and MCP-1, IL-12 (p40) and M-CSF for P. vivax infected patients may also prove useful in understanding age-associated and species-specific host immune responses, as could the species-specific differences in Ang-2. Regional differences in host immune response to malaria infection within the same species may speak to unique strains circulating in parts of West Africa.