Intermittent preventive treatment with sulfadoxine-pyrimethamine does not modify plasma cytokines and chemokines or intracellular cytokine responses to Plasmodium falciparum in Mozambican Children

IPTi-SP did not significantly affect the proportion of CD3+ cells producing IFN-γ, IL-4 or IL-10. Overall, plasma cytokine or chemokine concentrations did not differ between treatment groups. Th1 and pro-inflammatory responses were higher than Th2 and anti-inflammatory responses, respectively, and IFN-γ:IL-4 ratios were higher for placebo than for SP recipients. Levels of cytokines and chemokines varied according to age, declining from 5 to 9 months. Plasma concentrations of IL-10, IL-12 and IL-13 were associated with current infection or prior malaria episodes. Higher frequencies of IFN-γ and IL-10 producing CD3+ cells and elevated IL-10, IFN-γ, MCP-1 and IL-13 in plasma were individually associated with increased malaria incidence, at different time points. When all markers were analyzed together, only higher IL-17 at 12 months was associated with lower incidence of malaria up to 24 months.Our work has confirmed that IPTi-SP does not negatively affect the development of cellular immune response during early childhood. This study has also provided new insights as to how these cytokine responses are acquired upon age and exposure to P. falciparum, as well as their associations with malaria susceptibility.ClinicalTrials.gov: NCT00209795In 2009 there were an estimated 68,925,435 cases of malaria in the African region (78% of worldwide estimates) and 111,885 malaria deaths (91% of worldwide estimates) [1]. These figures demonstrate that Plasmodium falciparum malaria remains a major threat to the health of Africans, in particular children under 5 years of age. In malaria endemic areas, older children and adults develop immunity to severe morbidity and death, though remaining susceptible to infection [2,3]. Immunoglobulin passive transfer studies in humans suggest that antibodies are key mediators of naturally acquired immunity [4]. More recent data [5] suggest that cellular immunity also plays an important role in the protection against P. falciparum disease in humans [