Abstract
BackgroundImmunological Human African Trypanosomiasis (HAT) studies often exclude malaria, although both infections overlap in specific endemic areas. During this co-infection, it is not known whether this parasitic interaction induces synergistic or antagonistic cytokine response among humans. This study determined prevalence of Plasmodium falciparum malaria among Trypanosoma brucei rhodesiense HAT and plasma cytokine profile levels associated with HAT and/or malaria infections.MethodsParticipants were recruited at Lwala hospital in north eastern Uganda: healthy controls (30), malaria (28), HAT (17), HAT and malaria (15) diagnosed by microscopy and PCR was carried out for parasite species identification. Plasma cytokine levels of Interferon-gamma (IFN-γ), Tumour Necrosis Factor-alpha (TNF-α), Interleukin (IL)-6, IL-10 and Transforming Growth Factor-beta (TGF-β) were measured by sandwich Enzyme-Linked Immuno Sorbent Assay and data statistically analysed using Graphpad Prism 6.0.ResultsThe prevalence of P. falciparum malaria among T. rhodesiense HAT cases was high (46.8%). Malaria and/or HAT cases presented significant higher plasma cytokine levels of IFN-γ, TNF-α, IL-6, IL-10 and TGF-β than healthy controls (P < 0.05). Levels of IFN-γ, IL-6 and IL-10 were significantly elevated in HAT over malaria (P < 0.05) but no significant difference in TNF-α and TGF-β between HAT and malaria (P > 0.05). Co-infection expressed significantly higher plasma IFN-γ, IL-6, and IL-10 levels than malaria (P < 0.05) but no significant difference with HAT mono-infection (P > 0.05). The TNF-α level was significantly elevated in co-infection over HAT or malaria mono-infections (P < 0.05) unlike TGF-β level. Significant positive correlations were identified between IFN-γ verses TNF-α and IL-6 verses IL-10 in co-infection (Spearman’s P < 0.05).ConclusionsThe T. b. rhodesiense significantly induced the cytokine response more than P. falciparum infections. Co-infection led to synergistic stimulation of pro-inflammatory (IFN-γ, TNF-α), and anti-inflammatory (IL-6, and IL-10) cytokine responses relative to malaria mono-infection. Level of TNF-α partially indicates the effect induced by T. b. rhodesiense and P. falciparum mono-infections or a synergistic interaction of co-infections which may have adverse effects on pathogenesis, prognosis and resolution of the infections.Trial registration VCD-IRC/021, 26/08/2011; HS 1089, 16/01/2012
Highlights
Immunological Human African Trypanosomiasis (HAT) studies often exclude malaria, both infections overlap in specific endemic areas
Since 2004, this area has been affected by T. b. rhodesiense HAT which extended from the historical foci in the eastern part of the country [21]
Malaria is prevalent in north eastern Uganda that coincides with HAT [2]
Summary
Immunological Human African Trypanosomiasis (HAT) studies often exclude malaria, both infections overlap in specific endemic areas. Plasmodium and trypanosome infection may exist within a host concurrently [1, 2] This is because tsetse flies and mosquitoes that transmit HAT and malaria parasites respectively, share these specific co-endemic habitats [3]. This co-infection is of epidemiological and immunological importance, most studies focus on single-pathogen infections. HAT cases present clinical symptoms similar to those of malaria [4] This makes diagnosis and management of both diseases difficult in overlapping areas. HAT clinical symptoms and fatality are not significantly affected by malaria [1, 2]
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