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Immunoglobulin G antibodies to merozoite surface antigens are associated with recovery from chloroquine-resistant Plasmodium falciparum in Gambian children

Authors :
J. Ismaili
Rosalyn Ord
Anthony A. Holder
Fatoumatta Sisay-Joof
Colin J. Sutherland
Margaret Pinder
Matthew B. B. McCall
Rachel Hallett
Paul Milligan
Source :
Infection and Immunity, 74, 5, pp. 2887-93, Infection and Immunity, 74, 2887-93
Publication Year :
2006

Abstract

We examined the hypothesis that recovery from uncomplicated malaria in patients carrying drug-resistantPlasmodium falciparumis a measure of acquired functional immunity and may therefore be associated with humoral responses to candidate vaccine antigens. Gambian children with malaria were treated with chloroquine in 28-day trials, and recovery was defined primarily as the absence of severe clinical malaria at any time and absence of parasitemia with fever after 3 days. Plasma samples from these children were assayed by enzyme-linked immunosorbent assay for immunoglobulin G (IgG) to recombinant merozoite antigens: apical membrane antigen 1 (AMA-1) and the 19-kDa C-terminal region of merozoite surface protein 1 (MSP-119), including antigenic variants of MSP-119with double and triple substitutions. Antigen-specific IgG was more frequent in children who recovered, particularly that for MSP-119(age-adjusted odds ratios: 0.32 [95% confidence interval, 0.05, 1.87;P= 0.168] for AMA-1, 0.19 [0.03, 1.11;P= 0.019] for recombinant MSP-119, 0.24 [0.04, 1.31;P= 0.032] for the recombinant MSP-119double variant, and 0.18 [0.03, 0.97;P= 0.013] for the triple variant). IgG titers to MSP-119and to the triple variant were higher in plasma samples taken 7 days after chloroquine treatment from children who carried resistant parasites but recovered and remained parasite free. Moreover, in children who were parasitemic on day 14 or day 28, there was an age-independent relationship between parasite density and IgG to both MSP-119and the triple variant (coefficients of −0.550 and −0.590 andPvalues of 0.002 and 0.001, respectively). The results validate the use of this approach to identify antigens that are associated with protection from malaria.

Details

ISSN :
00199567
Database :
OpenAIRE
Journal :
Infection and Immunity, 74, 5, pp. 2887-93, Infection and Immunity, 74, 2887-93
Accession number :
edsair.doi.dedup.....9d5181bad807a12752550c55d0e96cd9