Development of Antibodies against Chondroitin Sulfate A-AdherentPlasmodium falciparumin Pregnant Women

Abstract

In areas where Plasmodium falciparum is endemic, pregnant women are at increased risk for malaria, and this risk is greatest during the first pregnancy. The placenta sequesters parasites that are able to cytoadhere to chondroitin sulfate A (CSA), a molecule expressed by the placental syncytiotrophoblast, while parasites from a nonpregnant host do not bind to CSA. Cytoadherence is mediated by the expression of variants of the P. falciparum-erythrocyte membrane protein 1 family. Each member of this molecule family induces antibodies that specifically agglutinate infected erythrocytes and inhibit their cytoadherence ability. We investigated whether the higher susceptibility of primigravidae was related to the lack of immune response towards CSA-binding parasites. In a cross-sectional study, primigravidae delivering with a noninfected placenta were less likely to have antibodies agglutinating CSA-binding parasites than multigravidae (P < 0.01). In contrast, parasites from nonpregnant hosts were as likely to be recognized by the sera from women of various parities. In a longitudinal study, at 6 months of pregnancy, antibodies against CSA-binding parasites were present in 31.8% of primigravidae and in 76.9% of secundigravidae (P = 0.02). The antibodies against CSA-binding parasites inhibited the cytoadherence of a CSA-adherent parasite strain to the human placental trophoblast. Our data support the idea that the higher susceptibility of primiparae is related to a lack of a specific immune response to placental parasites.

Pregnancy-Associated Malaria in Sudan: Prevalence and Possible Risk Factors

“…This could be explained by the fact that acquisition of immunity to malaria increases with successive pregnancies. Such immunity is thought to be due either to priming of memory T cells or to production of antibodies against P. falciparum chondroitin sulfate A (PfCSA) that prevent parasites' sequestration in the placenta [15,16,21]. The study also indicated that malaria parasite density decreased with increasing parity and age further reinforcing the belief that the ability to control malaria parasitemia is parity and/or agedependent.…”

Seasonal Variation in Direct Obstetric Mortality in Rural Senegal: Role of Malaria?

“…5 Sequestration of malaria parasites in the placenta may contribute to hypertensive diseases of pregnancy by reducing placental perfusion and oxidative stress, and exacerbating the placental changes associated with preeclampsia. 6 A hospital study in Dakar also suggested a causal link between malaria and hypertensive diseases of pregnancy; pre-eclampsia was more common in the rainy season, and women presenting with a malaria-infected placenta had a three-fold increase in the risk of pre-eclampsia compared with women whose placenta was not infected. 7 However, severe anemia during the rainy season due to nutritional deficiencies but also malaria could contribute to direct maternal mortality by complicating an obstetrical condition.…”

Antibodies among Men and Children to Placental-Binding Plasmodium falciparum-Infected Erythrocytes that Express var2csa

“…During pregnancy, a combination of adhesion to specific placental receptors and immune pressure selects for novel or rare IE variants that evade existing immunity. 10 Prior to, or at the commencement of the first pregnancy, individuals have lower levels of antibodies to variant surface antigens (VSA) expressed by placental isolates and CSA-binding IEs, 5,[11][12][13] compared with other isolates. After exposure in pregnancy, most women develop antibodies to these variants, 14,15 which are associated with reduced risk of maternal malaria and complications in some studies.…”