Search

Summary: Drug resistance to Plasmodium falciparum contributes to major health problems in central Africa and, as a consequence, poverty. We have analyzed the efficacy of three currently available antimalarial drugs to treat symptomatic, uncomplicated P. falciparum malaria in semiimmune adults living in Bangui, Central Republic of Africa. 210 consecutive individuals were enrolled in the survey, of which 45 were excluded. Those having received dihydroartemisin proved significantly less parasitemic than those having received quinine per os or sulfadoxin-pyrimethamin (χ2 = 16.93 ; p < 0.05), and 75 % recovered in two days compared to 57 and 44 %, respectively. The 25 % who did not recover benefited from a second cure with dihydroartemisin, which proved 100 % efficient. The most accurate protocol remains to be established by analyzing clinical and parasitological data and taking into account the economics of the country.

Cytophilic antibodies (Abs) play a critical role in protection againstPlasmodium falciparumblood stages, yet little is known about the parameters regulating production of these Abs. We used an in vitro culture system to study the subclass distribution of antigen (Ag)-specific immunoglobulin G (IgG) produced by peripheral blood mononuclear cells (PBMCs) from individuals exposed toP. falciparumor unexposed individuals. PBMCs, cultivated with or without cytokines and exogenous CD40/CD40L signals, were stimulated with a crude parasite extract, recombinant vaccine candidates derived from conserved Ags (19-kDa C terminus of merozoite surface protein 1 [MSP119], R23, and PfEB200), or recombinant Ags derived from the polymorphic Ags MSP1 block 2 and MSP2. NoP. falciparum-specific Ab production was detected in PBMCs from unexposed individuals. PBMCs from donors exposed frequently toP. falciparuminfections produced multiple IgG subclasses when they were stimulated with the parasite extract but usually only one IgG subclass when they were stimulated with a recombinant Ag. Optimal Ab production required addition of interleukin-2 (IL-2) and IL-10 for all antigenic preparations. The IgG subclass distribution was both donor and Ag dependent and was only minimally influenced by the exogenous cytokine environment. In vitro IgG production and subclass distribution correlated with plasma Abs to some Ags (MSP119, R23, and MSP2) but not others (PfEB200 and the three MSP1 block 2-derived Ags). Data presented here suggest that intrinsic properties of the protein Ag itself play a major role in determining the subclass of the Ab response, which has important implications for rational design of vaccine delivery.

In malaria endemic areas, pregnancy is assumed to be associated with a specific reduction in immunity to Plasmodium falciparum malaria. To understand some of the mechanisms which underlie such a poor immunity, we have attempted to examine the frequency and distribution of IgM and IgG antibodies to a crude antigenic extract of parasitized erythrocytes and to the merozoite surface protein-1 (MSP1), in a population of mothers compared to control non-pregnant women, all living in Dakar and suburbs. Specifically, this work describes: (i) the responses of mothers and control women; (ii) the balance between IgM and IgG responses; and (iii) responses to malarial antigen and to MSP1. An unexpected balance between P. falciparum-specific IgM and IgG is shown, associated with a substantial increase in anti-MSP1 IgM, and a decrease in anti-MSP1 IgG in parturients.