PLASMODIUM COATNEYI IN THE RHESUS-MONKEY (MACACA-MULATTA) AS A MODEL OF MALARIA IN PREGNANCY

Pregnant women with Plasmodium falciparum infection are at increased r isk for complications such as anemia and cerebral malaria. In addition , the infants of these women suffer intrauterine growth retardation (I UGR), low birth weight (LBW), congenital infection, and high infant mo rtality. Although much has been learned from studies of malaria during human pregnancy, progress has been limited by the lack of a suitable animal model. Nonhuman primates are of particular interest because, ot her than the armadillo, they are the only animals with a discoidal, vi llous, hemochorial placenta like that of humans. We have established a model of malaria during human pregnancy by inoculating pregnant rhesu s monkeys (Macaca mulatta) with Plasmodium coatneyi (a sequestering pa rasite) during the first trimester. In our initial experiment, four mo nkeys were inoculated with a fresh inoculum containing 10(8) viable pa rasites from an infected donor monkey. All four monkeys became parasit emic seven days postinoculation (PI) and three monkeys aborted 7-10 da ys PI coincident with high peak parasitemias (41,088-374,325 parasites /mm(3)). Although abortion is one of the outcomes observed in Plasmodi um-infected women, the intent of this study was to examine the effects of Plasmodium infection throughout gestation. Since the rapid onset o f high parasitemia may have been responsible for the abortions, a deci sion was made to reduce the size of the effective inoculum. Six additi onal pregnant monkeys were inoculated with a frozen isolate taken from the same donor containing 10(6) parasites. These six animals became p arasitemic by 14 days PI and, along with monkey E412, carried their in fants to term. These seven infants weighed significantly less at term than the infants of uninfected mothers (P = 0.0355). Sym metrical IUGR was detected by ultrasound in one fetus with an LBW of 334 g. Another LBW infant (300 g) had asymmetrical growth retardation, which has bee n associated with uteroplacental insufficiency and was consistent with the lower placental weights found in infected dams compared with cont rols (P = 0.0455). The infant with symmetric IUGR died at five days of age, while the other is alive but congenitally infected. The IUGR, LB W, congenital infection, postnatal infant mortality, and early abortio ns observed in these animals suggest that P. coatneyi in pregnant rhes us monkeys is a valid model of malaria in human pregnancy. This model should provide the opportunity to study questions about malaria in pre gnancy that have been difficult to study in humans.