Unravelling the patterns of host immune responses in Plasmodium vivax malaria and dengue co-infection

Abstract

Background: Concurrent malaria and dengue infection is frequently diagnosed in endemic countries, but its immunopathology remains largely unknown. In the present study, a large panel of cytokines/chemokines and clinical laboratory markers were measured in patients with Plasmodium vivax and dengue co-infection as well as in individuals with malaria or dengue mono-infections in order to identify biosignatures of each clinical condition. Methods: Individuals from the Brazilian Amazon were recruited between 2009 and 2013 and classified in three groups: vivax malaria (n = 52), dengue (n = 30) and vivax malaria and dengue co-infection (n = 30). P. vivax malaria was diagnosed by thick blood smear and confirmed by PCR; dengue cases were detected by IgM ELISA or NS1 protein. The plasma levels of cytokines and chemokines were determined by multiplex assay. Results: Individuals with malaria and dengue co-infection displayed lower levels of platelets and haemoglobin than those with malaria or dengue mono-infections (p = 0.0047 and p = 0.0001, respectively). The group of individuals co-infected exhibited the highest median concentrations of IFN-γ, IL-6, CCL4 than the mono-infected groups. Network analyses of plasma cytokines/chemokines revealed that malaria and dengue co-infection exhibits a distinct immune profile with critical roles for TNF, IL-6 and IFN-γ. Further, parasitaemia levels displayed positive significant interactions with IL-6, CCL4 and IL-10 in the group of patients co-infected with malaria and dengue. No differences were observed in distribution of dengue virus serotypes and Plasmodium parasitaemia levels between the groups. Conclusions: The findings described here identify unique patterns of circulating immunological markers in cases of malaria and dengue co-infection and provide insights on the immunopathology of this co-morbid condition.