Low antibodies against Plasmodium falciparum and imbalanced pro-inflammatory cytokines are associated with severe malaria in Mozambican children: a case-control study (Malaria Journal)

Background: The factors involved in the progression from Plasmodium falciparum infection to severemalaria (SM) are still incompletely understood. Altered antibody and cellular immunityagainst P. falciparum might contribute to increase the risk of developing SM. Methods: To identify immune responses associated with SM, a sex- and age-matched case-controlstudy was carried out in 134 Mozambican children with SM (cerebral malaria, severeanaemia, acidosis and/or respiratory distress, prostration, hypoglycaemia, multiple seizures)or uncomplicated malaria (UM). IgG and IgM against P. falciparum lysate, merozoiteantigens (MSP-119, AMA-1 and EBA-175), a Duffy binding like (DBL)-alpha rosetting domainand antigens on the surface of infected erythrocytes were measured by ELISA or flowcytometry. Plasma concentrations of IL-12p70, IL-2, IFN-gamma, IL-4, IL-5, IL-10, IL-8, IL-6, IL-1beta, TNF, TNF-beta and TGF-beta1 were measured using fluorescent bead immunoassays. Datawas analysed using McNemar`s and Signtest. Results: Compared to UM, matched children with SM had reduced levels of IgG against DBLalpha(P < 0.001), IgM against MSP-119 (P = 0.050) and AMA-1 (P = 0.047), TGF-beta1 (P