Cytokine profiles in adults with imported malaria: insights from the PALUREA cohort study

Abstract Introduction. Given the increase in worldwide exchanges, imported malaria is a growing health concern in non-endemic countries. Most data regarding malaria pathophysiology arises from endemic areas, and little is known about cytokine profiles during imported malaria. Methods. We presented here the cytokines results of the PALUREA cohort study, which was conducted in France between 2006 and 2010. Adult patients were dichotomized between severe malaria (SM) and uncomplicated malaria (UM), and two subgroups were further defined in the SM group: very severe malaria (VSM) and less severe malaria (LSM). On hospital admission, cytokine blood tests were performed in duplicate using Luminex technology for eight cytokines: Interleukin (IL)-1a, IL-1ß, IL-2, IL-4, IL-10, Tumor necrosis factor (TNF)-a, Interferon (IFN)γ and Macrophage migration inhibitory factor (MIF). For SM patients, repeated tests were made during the first 2 days following admission. Results. 278 patients were included in the cytokine analysis: 134 with UM and 144 with SM. For IL-1a, IL-1b, IL-2, IL-4, IFNγ and TNF-a, more than 50% of patients had undetectable levels on hospital admission, when IL-10 and MIF were significantly higher in severe cases. IL-10 was significantly associated with parasitemia (R=0.32 [0.16 ; 0.46]; p = 0.0001). Patients with elevated IL-10 during the first days of ICU stay were more prone to develop subsequent secondary infections. Conclusion. Among the 8 tested cytokines, only MIF and IL-10 were associated with disease severity among adult patients with imported plasmodium falciparum malaria. On admission, many patients had undetectable cytokine level, which suggests that assessment of circulating cytokines levels is not relevant in routine evaluation of malaria patients.