Lack of association between maternal antibody and protection of African infants from malaria infection

Abstract

Maternally derived antibodies are believed to protect infants against infection, but there is little direct evidence for a protective role of passively acquired antibodies against malaria. A longitudinal study of malaria infection in 143 infants was conducted in a region of southern Ghana where Plasmodium falciparum is endemic. Infants born in the high-transmission season were less likely to become infected in the first 20 weeks of life than children born in the low-transmission season. Plasma, obtained at birth, was tested for immunoglobulin G (IgG) and IgG subclasses to P. falciparum schizonts and recombinant circumsporozoite antigen, MSP-1(19), MSP-2, AMA-1, and Pf155 (also called ring-infected erythrocyte surface antigen). Antibody levels at birth were not associated with resistance to malaria infection. On the contrary, antibodies at birth were positively associated with infection, indicating that high levels of maternally derived antibodies represent a marker for intensity of exposure to malaria infection in infants. However, all five children who experienced high-density infections (>100 parasites/microl of blood) were seronegative for MSP-1(19) at the time of infection.

FIG. 1

Rate of malaria infection by age. Rate of infections per 100 clinic visits, where infection is defined as a specimen that is blood film positive or PCR positive or as a twofold increase in OD for IgG to crude schizont antigen. ▴, includes congenital infections; ●, excludes congenital infections.

FIG. 2

Levels of IgG antibody to P. falciparum antigens in children at birth. Box, interquartile range; line through box, median; error bars, 95% confidence interval range; individual symbols, values lying outside the 95% range; Ag, antigen.

FIG. 3

Maternally derived IgG antibodies to P. falciparum schizont antigen. (a) Comparison of OD values for IgG in mothers' sera during pregnancy (y axis) and children's sera at birth (x axis). (b) Comparison of rates of decay of maternally derived IgG in children with above- or below-median levels of antibody at birth. Proportions of children remaining antibody positive (y axis) over time (in weeks) (x axis) are shown. The difference between the two plots is statistically significant (Cox's proportional-hazards regression, P < 0.001).