Antibodies to variant surface antigens of plasmodium falciparum-infected erythrocytes are associated with protection from treatment failure and the development of anemia in pregnancy

Abstract

Background. In pregnancy-associated malaria (PAM), Plasmodium falciparum-infected erythrocytes (IEs) express variant surface antigens (VSA-PAM) that evade existing immunity and mediate placental sequestration. Antibodies to VSA-PAM develop with gravidity and block placental adhesion or opsonize IEs for phagocytic clearance, helping to prevent maternal anemia and low birth weight in infants. Methods. Using serum samples from 141 pregnant Malawian women with parasitemia enrolled in a randomized trial of antimalarials and VSA-PAM-expressing CS2 IEs, we quantified levels of immunoglobulin (Ig) G to VSAPAM by flow cytometry and levels of opsonizing antibodies by measuring uptake of IEs by THP1 promonocytes. Results. After controlling for gravidity and antimalarial treatment, higher levels of IgG to VSA-PAM were associated with decreased anemia at delivery (odds ratio [OR], 0.66 [95% confidence interval {CI}, 0.46-0.93]; P = .018) and were weakly associated with decreased parasitological failure (OR, 0.78 [95% CI, 0.60-1.03]; P = .075), especially reinfection (OR, 0.73 [95% CI, 0.53-1.01]; P = .057). Higher levels of opsonizing antibodies to CS2 IEs were associated with less maternal anemia (OR, 0.31 [95% CI, 0.13-0.74]; P = .008) and treatment failure (OR, 0.48 [95% CI, 0.25-0.90]; P = .023), primarily because of recrudescent infection (OR, 0.49 [95% CI, 0.211.12]; P= .089). Conclusion. Higher levels of both IgG antibodies to VSA-PAM and opsonizing antibodies, a functional measure of immunity, correlate with parasite clearance and less anemia in pregnancy malaria. © 2009 by the Infectious Diseases Society of America. All rights reserved.