Editorial Commentary: Plasmodium vivax Infection during Pregnancy: An Important Problem in Need of New Solutions

Abstract

Plasmodium vivax, the most widespread parasite causing human malaria, is responsible for an estimated 130–435 million infections annually and is the major cause of malaria in most of Asia and Latin America [1, 2]. Although P. vivax infection is commonly considered to be much more benign than Plasmodium falciparum infection, historical evidence suggests significant mortality associated with P. vivax malaria in the pre-antimalarial era [3], and death caused by P. vivax malaria has been increasingly recognized over the past few years [1, 4, 5]. In this issue of Clinical Infectious Diseases, Poespoprodjo et al. [6] report the impact of P. vivax infection on pregnancy outcomes in Papua, Indonesia. Of 50 million pregnancies occurring each year in countries where malaria is endemic, approximately one-half occur in areas where P. vivax malaria is endemic [7]. P. falciparum malaria during pregnancy is a well-known cause of maternal and fetal morbidity and mortality. Each year, an estimated 10,000 maternal deaths result from malarial anemia, and 60–200,000 infant deaths result from malaria-associated low birth weight in Africa. In areas of low transmission, such as in many areas of Latin America and the Asia-Pacific region (and where adults migrate from malaria-free areas to areas of endemicity), pregnant women may have limited prepregnancy immunity and may be susceptible to symptomatic and severe disease [8]. Symptomatic malaria may lead to preterm delivery and fetal loss, and neonates of nonimmune mothers may be at a particular risk of congenital malaria resulting from transplacental passage of parasites. Although P. vivax infection during pregnancy has been recognized for many years [9], the impact of such infection during pregnancy has been assessed only recently. In series from Thailand and India, women with P. vivax infection were more commonly anemic and delivered lower birth weight neonates, compared with uninfected women, but the effects were less pronounced than those associated with P. falciparum infection [10, 11]. In both studies, P. vivax infection was most common during the first pregnancy, and the prevalence of such infection peaked early during the second trimester. The study from Papua, Indonesia, by Poespoprodjo et al. [6] adds further support for a significant impact of P. vivax malaria on outcomes of pregnancy. Of 2570 women who delivered in a district hospital, 16.8% were parasitemic at delivery; of these parasitemic women, 58% and 34% had monoinfections due to P. falciparum and P. vivax, respectively, and the remainder had mixed infections. As expected, P. falciparum malaria was associated with a considerable decrease in birth weight (192 g) and a 2.8-fold increase in the odds of severe anemia (hemoglobin concentration, <7 g/dL). Although the effects of P. vivax malaria were less pronounced than the effects of P. falciparum malaria, women with P. vivax infection also delivered neonates with lower birth weights (108 g) and were more likely to have anemia (OR, 1.8), compared with uninfected women, despite the much lower parasite densities and the absence of fever in three-quarters of women with P. vivax infection. Having fever was associated with an increased probability of preterm delivery and severe anemia. Because preterm labor and low birth weight are key determinants of infant health, the 1.9-fold increased odds of low birth weight associated with P. vivax infection may also have important indirect consequences on child survival. Differences between P. vivax and P. falciparum are relevant to understanding the pathogenesis of infections due to these species during pregnancy. P. vivax infects only reticulocytes, invading them after binding of merozoites to the Duffy antigen-receptor for chemokines; when this protein is lacking (a common finding in African populations), infection does not occur. Predilection for reticulocytes limits parasitemia, whereas P. falciparum parasite load may increase to much higher levels. In addition, most importantly for pregnant women, P. vivax–infected erythrocytes do not express erytrocyte surface proteins that allow them to sequester in the host vasculature. In pregnant women, placental sequestration of P. falciparum can lead to high local parasite load, often associated with inflammatory response [12], which has been implicated in the pathogenesis of low birth weight and anemia [13]. In 1 study, the placental pathology in P. vivax infection was modest, and sequestration was absent [14]. This suggests that systemic infection in the mother, rather than local placental inflammation, may be responsible for the reported effects of P. vivax. Unlike P. falciparum infection, which has its greatest effect on birth weight during first pregnancies, P. vivax infection is associated with low birth weight during second and subsequent pregnancies [11]. This also suggests that mechanisms controlling parity-dependent immunity to P. falciparum infection, including development of