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


Pinder, M; Sutherland, CJ; Sisay-Joof, F; Ismaili, J; McCall, MBB; Ord, R; Hallett, R; Holder, AA; Milligan, P; (2006) Immunoglobulin G antibodies to merozoite surface antigens are associated with recovery from chloroquine-resistant Plasmodium falciparum in gambian children. Infection and immunity, 74 (5). pp. 2887-2893. ISSN 0019-9567 DOI: 10.1128/IAI.74.5.2887-2893.2006

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Abstract

We examined the hypothesis that recovery from uncomplicated malaria in patients carrying drug-resistant Plasmodium falciparum is 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-1(19)), including antigenic variants of MSP-1(19) with double and triple substitutions. Antigen-specific IgG was more frequent in children who recovered, particularly that for MSP-1(19) (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-1(19), 0.24 [0.04, 1.31; P = 0.032] for the recombinant MSP-1(19) double variant, and 0.18 [0.03, 0.97; P = 0.013] for the triple variant). IgG titers to MSP-1(19) and 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-1(19) and the triple variant (coefficients of -0.550 and -0.590 and P values 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.

Item Type: Article
Keywords: Molecular marker, protective immunity, malaria morbidity, serum, antibodies, parasite density, protein-1, responses, surveillance, specificity, artesunate, Animals, Antibodies, Protozoan, blood, Antigens, Protozoan, immunology, Antimalarials, pharmacology, Child, Child, Preschool, Chloroquine, pharmacology, Humans, Immunoglobulin G, blood, Infant, Malaria Vaccines, immunology, Malaria, Falciparum, drug therapy, immunology, parasitology, Membrane Proteins, immunology, Merozoite Surface Protein 1, immunology, Parasitemia, immunology, Plasmodium falciparum, drug effects, immunology, Protozoan Proteins, immunology, Research Support, Non-U.S. Gov't, Retrospective Studies
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: Antimicrobial Resistance Centre (AMR)
Malaria Centre
Tropical Epidemiology Group
PubMed ID: 16622227
Web of Science ID: 237311200043
URI: http://researchonline.lshtm.ac.uk/id/eprint/11839

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