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Infection and Immunity, May 2006, p. 2887-2893, Vol. 74, No. 5
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.5.2887-2893.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Immunoglobulin G Antibodies to Merozoite Surface Antigens Are Associated with Recovery from Chloroquine-Resistant Plasmodium falciparum in Gambian Children

Margaret Pinder,1* Colin J. Sutherland,3 Fatoumatta Sisay-Joof,1 Jamila Ismaili,1 Matthew B. B. McCall,2 Rosalyn Ord,3 Rachel Hallett,3 Anthony A. Holder,4 and Paul Milligan1,3

Medical Research Council Laboratories, Banjul, The Gambia,1 University of Nijmegen, Nijmegen, The Netherlands,2 London School of Hygiene and Tropical Medicine, London, United Kingdom,3 Division of Parasitology, National Institute for Medical Research, Mill Hill, London, United Kingdom4

Received 15 June 2005/ Returned for modification 26 August 2005/ Accepted 22 February 2006

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-119), including antigenic variants of MSP-119 with 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-119 double variant, and 0.18 [0.03, 0.97; P = 0.013] for the triple variant). IgG titers to MSP-119 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-119 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.

* Corresponding author. Mailing address: MRC Laboratories, P.O. Box 273, Banjul, The Gambia. Phone: (220) 4495917. Fax: (220) 4495919. E-mail: mpinder{at}qanet.gm.

Editor: J. F. Urban, Jr.

Infection and Immunity, May 2006, p. 2887-2893, Vol. 74, No. 5
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.5.2887-2893.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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