Abstract

BackgroundConcurrent 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.MethodsIndividuals 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.ResultsIndividuals 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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0835-8) contains supplementary material, which is available to authorized users.

Highlights

  • Concurrent malaria and dengue infection is frequently diagnosed in endemic countries, but its immunopathology remains largely unknown

  • The majority of individuals infected with dengue had DENV2 serotype with no differences in distribution of virus serotypes in the groups of individuals with dengue or dengue and malaria co-infection (Table 1)

  • It was observed that P. vivax parasitaemia displayed positive significant interactions with IL-6, chemokine C–C motif ligand 4 (CCL4) and IL-10 in the group of patients co-infected with malaria and dengue, while this parameter exhibited several positive correlations with many immune markers (GCSF, chemokine C–C motif ligand 2 (CCL2), CCL4, tumour necrosis factor (TNF), IL-12p70, IL-10, IL-6, and IL-4) in the group of malaria mono-infected subjects, suggesting a major role for parasitaemia in the immune profile in this clinical condition (Fig. 3b)

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Summary

Introduction

Concurrent malaria and dengue infection is frequently diagnosed in endemic countries, but its immunopathology remains largely unknown. 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 individu‐ als with malaria or dengue mono-infections in order to identify biosignatures of each clinical condition. It is estimated that two-fifths of the world population are at risk of dengue fever with 50–100 million cases each year worldwide [2, 3]. Both malaria and dengue fever exhibit dramatically similar. Observations from a case series of patients with dual malaria and dengue infections performed at the Brazilian Amazon indicated that coinfection can potentially result in a more severe disease presentation [10].

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