Increased Susceptibility to Plasmodium falciparum in Infants is associated with Low, not High, Placental Malaria Parasitemia

Risk of malaria in infants can be influenced by prenatal factors. In this study, the potential for placental parasitemia at delivery in predicting susceptibility of infants to Plasmodium falciparum (Pf) infections was evaluated. Seventy-two newborns of mothers who were placental malaria negative (PM-) and of mothers who were PM+ with below (PM+ Lo) and above (PM + Hi) median placental parasitemia, were actively monitored during their first year of life. Median time to first PCR-detected Pf infection was shorter in PM + Lo infants (2.8 months) than in both PM- infants (4.0 months, p = 0.002) and PM + Hi infants (4.1 months, p = 0.01). Total number of new infections was also highest in the PM + Lo group. Only 24% of infants experienced clinical malaria episodes but these episodes occurred earlier in PM + Lo infants than in PM + Hi infants (p = 0.05). The adjusted hazard ratio (95% CI) of having Pf infection was 3.9 (1.8-8.4) and 1.5 (0.7-3.4) for infants in the PM + Lo and PM + Hi groups, respectively. Collectively, low placental parasitemia was associated with increased susceptibility to malaria during infancy. Therefore, malaria in pregnancy preventive regimens, such as sulfadoxine-pyremethamine, that reduce but do not eliminate placental Pf in areas of drug resistance may increase the risk of malaria in infants.