Phenotypes of Plasmodium falciparum from the Peripheral Blood of Pregnant Women

In a recent paper in Infection and Immunity, Ofori et al. (7) reported interesting findings suggesting that P. falciparum-infected erythrocytes in the peripheral circulation express variant surface antigens typical of placental parasites; parasitized erythrocytes from the peripheral blood of pregnant women in Ghana were recognized by serum immunoglobulin G in the same gender- and parity-specific manner as that reported for placental-type parasitized erythrocytes (2, 5). We wish to highlight some related findings relevant to understanding the pathogenesis and immunology of maternal malaria.

In Malawian women, studies of developmental stages of placental and peripheral blood parasites suggest that most placental parasites do not undergo a full cycle of replication in the placenta but circulate and specifically sequester during the later developmental stages (1), consistent with the report of Ofori et al. In addition, there was an association between the adhesion phenotypes of placental isolates and peripheral blood isolates (2) binding predominantly to chondroitin sulfate A (CSA). However, several other findings suggest important differences between the circulating and sequestered parasite populations in pregnant women. Placental and peripheral blood parasite populations often appear to be genetically different (6), and a comparison between placental and peripheral isolates from the same individuals demonstrated differences in adhesion phenotypes and serum antibody recognition with some paired isolates (2). In addition, many peripheral blood isolates form rosettes, but rosetting is almost completely absent among placental parasites (8), and a greater proportion of peripheral than placental isolates appear to bind to CD36 (2, 4). Interestingly, preliminary data suggested that fewer peripheral blood isolates collected from pregnant women at delivery bound to CSA than those collected mid-pregnancy (2), a finding which may warrant further investigation. Therefore, although peripheral blood isolates appear to be representative of placental parasites, they should not be assumed to be the same. Taken together, these observations suggest that circulating peripheral blood isolates comprise parasitized erythrocytes with mixed phenotypes that derive from other sequestered parasite populations, in addition to placental parasites, which may differ among individuals and in populations with differing levels of background immunity.

We propose that the gender and gravidity associations with antibodies to peripheral blood isolates from pregnant women may relate not only to CSA-binding phenotypes but also to other phenotypes. In areas of moderate-to-high malaria transmission, women acquire substantial immunity prior to pregnancy. Apart from positive selection for adhesion in the placenta, there might be selection for particular variants that are poorly recognized by existing antibodies, exploiting gaps in the repertoire of variant-specific immunity (2-5). Therefore, there may be novel antigenic phenotypes in the peripheral blood in addition to those that adhere to CSA (3). Identifying the properties and determining the prevalence of these phenotypes may be highly informative for understanding the immunology and pathogenesis of maternal malaria.