Comparison of Antibody Responses and Parasite Clearance in Artemisinin Therapeutic Efficacy Studies in the Democratic Republic of Congo and Asia

Abstract

Background: Understanding the effect of immunity on Plasmodium falciparum clearance is essential for interpreting therapeutic efficacy studies designed to monitor emergence of artemisinin drug resistance. In low-transmission areas of Southeast Asia, where resistance has emerged, P. falciparum antibodies confound parasite clearance measures. However, variation in naturally acquired antibodies across Asian and sub-Saharan African epidemiological contexts and their impact on parasite clearance re yet to be quantified.

Methods: In an artemisinin therapeutic efficacy study, antibodies to 12 pre-erythrocytic and erythrocytic P. falciparum antigens were measured in 118 children with uncomplicated P. falciparum malaria in the Democratic Republic of Congo (DRC) and compared with responses in patients from Asian sites, described elsewhere.

Results: Parasite clearance half-life was shorter in DRC patients (median, 2 hours) compared with most Asian sites (median, 2-7 hours), but P. falciparum antibody levels and seroprevalences were similar. There was no evidence for an association between antibody seropositivity and parasite clearance half-life (mean difference between seronegative and seropositive, -0.14 to +0.40 hour) in DRC patients.

Conclusions: In DRC, where artemisinin remains highly effective, the substantially shorter parasite clearance time compared with Asia was not explained by differences in the P. falciparum antibody responses studied.

Keywords: antibodies; artemisinin; malaria; parasite; resistance.

Figure 1.

Immunoglobulin (Ig) G responses to Plasmodium falciparum antigens in the Tracking Resistance to Artemisinin Collaboration (TRAC) study participants from Kinshasa, Democratic Republic of Congo. A, Dots represent individual IgG responses to selected recombinant P. falciparum antigens; black horizontal lines, medians; and whiskers, interquartile ranges. Abbreviation: MFI, mean flourescence intensity; OD, optical density. B, Seroprevalences of IgG antibody responses to each antigen. Sporozoite antigen is shown in orange, merozoite surface proteins (MSPs) in dark green and rhoptry/microneme proteins in light green (measured by enzyme-linked immunosorbent assay), and variant surface antigens on 3D7-infected erythrocytes in blue (measured by flow cytometry). Seropositivity cutoffs for each antigen were as follows: circumsporozoite protein (CSP), 0.40; MSP1₁₉, 0.27; MSP2_FC27, 0.03; MSP2_3D7, 0.07; MSP3, 0.14; MSP6, 1.15; MSP7, 0.17; apical membrane antigen 1 (AMA1), 0.07; erythrocyte-binding antigen (EBA) 175, region 2 (EBA175_RII), 0.11; EBA 175, regions 3–5, EBA175_RIII-, 0.07; reticulocyte-binding ligand homologue 2 (Rh2), 0.30; and VSA 3D7 336.1. Abbreviation: CI, confidence interval.