HIF-1α regulated pathomechanism of low birth weight through angiogenesis factors in placental Plasmodium vivax infection.

Background: Malaria in pregnancy leads to placental malaria. The primary pathogenesis of the complex fetal implications in placental malaria is tissue hypoxia due to sequestrations of Plasmodium falciparum-infected erythrocytes in the placenta. However, the pathomechanism of placental Plasmodium vivax infection has not been thoroughly investigated. Hypoxia-inducible factor-1α (HIF-1α) is a key transcriptional mediator of the response to hypoxic conditions, which interacts with the change and imbalances of many chemical mediators, including angiogenic factors, leading to fetal growth abnormality. Methods: This study was conducted cross-sectionally in Maumere, Sikka Regency, East Nusa Tenggara Province, previously known as one of the malaria endemic areas with a high incidence of low birth weight (LBW) cases. This study collected peripheral and umbilical blood samples and placental tissues from mothers who delivered their babies with LBW at the TC Hiller Regional Hospital. All of the blood samples were examined for parasites by microscopic and PCR techniques, while the plasma levels of VEGF, PlGF, VEGFR-1, VEGFR-2, and HIF-1α were determined using ELISA. The sequestration of infected erythrocytes and hemozoin was determined from placental histological slides, and the expression of placenta angiogenic factors was observed using the immunofluorescent technique. Results: In this study, 33 cases had complete data to be analyzed. Of them, 19 samples were diagnosed as vivax malaria and none of falciparum malaria. There were significant differences in Δ 10th percentile growth curve of baby's body weights and also all angiogenic factors in placental tissues {VEGF, PlGF, and VEGFR-1, VEGFR-2, and HIF-1α} between those infected and not infected cases (p<0.05), but not for VEGF and VEGFR-2 in the plasma. Conclusion: This study indicated that Plasmodium vivax sequestration may promote LBW through alterations and imbalances in angiogenic factors led by HIF-1α.

The Relationship Between Fetal Weight with Sequestration of Infected Erythrocyte, Monocyte Infiltration, and Malaria Pigment Deposition in Placenta of Mother Giving Birth Suffering from Plasmodium Vivax Infection.

BACKGROUND: Malaria in pregnancy can cause fatal complications by parasite sequestration mechanism, which can cause monocyte infiltration in the intervillous space. P. vivax infection was significantly associated with malaria pigment in the placenta, indicating past subclinical infections. OBJECTIVE: This study aimed to determine the mechanism of P. vivax in the pathogenesis of placental malaria and its relationship with LBW. METHODS: This study was observational analytic with a cross-sectional approach. Placental tissue samples were obtained from pregnant women with LBW babies during delivery in Maumere, Nusa Tenggara Timur. The samples used in this study were confirmed by a polymerase chain reaction and consisted of 25 samples with 12 positive and 13 negative samples. Placental tissue samples were made with Hematoxylin-Eosin staining and observed under 1000x magnification at 100 fields using a light microscope. Parasite density, monocyte infiltration, and parasite pigments deposition were calculated. RESULTS: Microscopic observation revealed that there was a significant difference in infected erythrocytes sequestration between groups. Interestingly, monocyte and malaria pigments accumulation were found in malaria-positive and -negative groups, and no significant difference between groups. The correlation test showed no significant relationship between monocyte infiltration and LBW in the malaria-positive and -negative group and between parasite pigments and LBW in both groups. Moreover, there was no significant correlation between parasite density and LBW in the positive and negative groups. CONCLUSION: P. vivax infection causes acute, sub-acute, and chronic placental malaria in subclinical infected pregnant women in Maumere, Nusa Tenggara Timur that might cause an LBW baby.