A RHESUS MONKEY MODEL OF MALARIA DURING PREGNANCY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The associated factors responsible for the increased severity of clinical malaria in pregnant women and its associated fetal complications such as low birth weight (LBW) are unknown. A study utilizing 32 rhesus monkeys of differing parities through 3 sequential pregnancies with malaria (Plasmodium coatneyi) began in 2000 and ended in 2006 with a total of 104 chronic infections (113 days). Repeated infections in the same monkey represented different levels of malaria immunity. Parasitemia, CBCs, FACS data, and clinical signs were monitored and fetal growth and development evaluated by ultrasonography. The infants, placentas, cord blood, maternal blood, and amniotic fluid were collected during cesarean section. Correlates of increased or decreased severity of malaria and its effect on the fetus/infant were identified. Features of poor infant outcome (PIO) in controls included: low weight mother, small placenta, LBW, symmetric intrauterine growth retardation (IUGR), and no associated placental pathology other than chorioamnionitis. PIO in malaria-infected pregnancies included: high parasites, small placenta, fetal death, LBW, symmetric and asymmetric IUGR, insufficient progesterone and estradiol, low maternal weight, and increased malaria-associated placental pathology. Pregnancy-related and malaria-induced immunosuppression and immunopathology were identified though FACS analysis (published 2005) and assessment of maternal serum cytokines. We determined peripheral blood serum levels of TNF alpha, its soluble receptors, STNFR1 and STNFR2, throughout primigravid pregnancy, malaria infection and a combination of the two. TNF alpha was always associated with fetal death and soluble TNF receptors appear to be important for fetal protection possibly through neutralizing the toxic effects of TNF alpha. Our findings showed that increased STNFR2 was associated specifically with malaria and not normal pregnancy or even pregnancy with LBW due to chorioamnionitis. In contrast, elevations in STNFR1 during the later half of normal pregnancy indicate that it may be important in regulating TNF alpha in preparation for normal labor and delivery (in press).