Abstract
BackgroundPlasmodium vivax is the causative agent of human malaria of large geographic distribution, with 35 million cases annually. In Brazil, it is the most prevalent species, being responsible by around 70 % of the malaria cases.MethodsA cross-sectional study was performed in Manaus (Amazonas, Brazil), including 36 adult patients with primary malaria, 19 with recurrent malaria, and 20 endemic controls. The ex vivo phenotypic features of circulating leukocyte subsets (CD4+ T-cells, CD8+ T-cells, NK, NKT, B, B1 and Treg cells) as well as the plasmatic cytokine profile (IL-2, IL-4, IL-6, IL-10, TNF and IFN-γ) were assessed, aiming at establishing patterns of immune response characteristic of primary malaria vs recurrent malaria as compared to endemic controls.ResultsThe proportion of subjects with high levels of WBC was reduced in malaria patients as compared to the endemic control. Monocytes were diminished particularly in patients with primary malaria. The proportion of subjects with high levels of all lymphocyte subsets was decreased in all malaria groups, regardless their clinical status. Decreased proportion of subjects with high levels of CD4+ and CD8+ T-cells was found especially in the group of patients with recurrent malaria. Data analysis indicated significant increase in the proportion of the subjects with high plasmatic cytokine levels in both malaria groups, characterizing a typical cytokine storm. Recurrent malaria patients displayed the highest plasmatic IL-10 levels, that correlated directly with the CD4+/CD8+ T-cells ratio and the number of malaria episodes.ConclusionThe findings confirm that the infection by the P. vivax causes a decrease in peripheral blood lymphocyte subsets, which is intensified in the cases of “recurrent malaria”. The unbalanced CD4+/CD8+ T-cells ratio, as well as increased IL-10 levels were correlated with the number of recurrent malaria episodes. These results suggest that the gradual remodelling of the immune response is dependent on the repeated exposure to the parasite, which involves a strict control of the immune response mediated by the CD4+/CD8+ T-cell unbalance and exacerbated IL-10 secretion.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1501-5) contains supplementary material, which is available to authorized users.
Highlights
Plasmodium vivax is the causative agent of human malaria of large geographic distribution, with 35 million cases annually
Data analysis did not demonstrate any significant difference in the red blood cell (RBC) counts, haemoglobin levels and haematocrit amongst patients with malaria and the endemic controls
The white blood cell (WBC) counts by multiple comparisons showed a reduction in both groups with malaria in relation to the endemic control individuals (p = 0.018)
Summary
Plasmodium vivax is the causative agent of human malaria of large geographic distribution, with 35 million cases annually. The recurrence of P. vivax malaria is a phenomenon that commonly occurs within a few months after the treatment of primary infection. The recurrence is defined as the reappearance of asexual forms of the parasite in the blood, up to 6 months after post-therapeutic monitoring period [13]. Relapse/recrudescence may occur for different reasons such as resistance of the parasite to the chemotherapy used [14], therapeutic failure, non-adherence to the treatment [15] and reactivation of the hypnozoites [16]. Recurrence has been rather considered a new malaria episode occurring in endemic areas after effective therapeutic intervention [17]
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