603: Association between parity and hemozoin-positive syncytiotrophoblasts and CD68+ cells in Plasmodium falciparuminfected placentas

Plasmodium falciparum malaria infection during pregnancy is estimated to account for up to 50% of low birth weight infants in endemic areas. P. falciparum-infected red blood cells sequester in the intervillous space of the placenta, and the malaria pigment hemozoin has been noted within intervillous maternal monocytes/macrophages, syncytiotrophoblasts (STBs) and villous mesenchymal cells. We aimed to further characterize these histopathological features of infection to identify potential pathophysiological mechanisms of placental malaria. We performed immunolocalization studies on 34 biopsies of P. falciparum-infected and uninfected placentas (n=17/group) from the Democratic Republic of the Congo. A diagnosis of malaria was made at the time of delivery. Patients with other pregnancy complications, including hypertension, preeclampsia, chorioamnionitis, and maternal anemia, were excluded. Placental sections were scored for the number of pigmented STBs and mesenchymal cells per 400x field. Immunostaining with cytokeratin 7 (KRT7) and CD68 demonstrated that hemozoin was present within STBs and monocytes/macrophages, respectively. Regression analysis suggested that hemozoin-positive STBs and CD68+ cells were associated with placentas from primigravidae and secundigravidae. Quantification of intravillous CD68+ cells, corresponding to fetal Hofbauer cells, revealed an increased prevalence in infected placentas from first and second pregnancies, compared to uninfected, parity-matched controls. Interestingly, we did not observe an increase in CD68+ cells in case versus control placentas from multigravidae (parity ≥ 3). These data suggest that STBs and CD68+ fetal Hofbauer cells engulf hemozoin or P. falciparum-infected RBCs. Furthermore, our findings of increased numbers of intravillous CD68+ Hofbauer cells in placentas from primigravidae and secundigravidae may suggest a heightened fetal immune response in these patients, which are more susceptible to severe complications from placental malarial.