ABSTRACT
In endemic areas, pregnancy increases susceptibility to P. falciparum and P. vivax, but not P. malariae, and this susceptibility diminishes with successive pregnancies. Immunomodulation occurs during pregnancy, but does not predict the distinct epidemiology of pregnancy malaria, suggesting that susceptibility may be due to factors other than immunosuppression. Malaria itself causes immunosuppression, complicating efforts to define altered immune responses as a cause or an effect of increased susceptibility. Non-immunologic host-parasite interactions can also influence susceptibility. For example, P. vivax episodes may increase due to the reticulocytosis of pregnancy and, paradoxically, the increased use of antimalarials. P. falciparum exploits the placenta as a new site for sequestration, and falciparum parasites in the placenta have a distinct adhesive and antigenic phenotype. Antibodies that inhibit parasite adhesion in the placenta are associated with protection from P. falciparum, and these antibodies are acquired over successive pregnancies, explaining the high susceptibility of primigravidae. Specific immunity limits the accumulation of falciparum parasites and inflammatory cells in the placenta, leading to improved pregnancy outcomes. A vaccine that targets placental parasites may confer protection from falciparum malaria during pregnancy.
