Meet Kobia’s research team

Project details:

Because placental malaria is not detectable by conventional means like analysis of maternal peripheral blood by microscopy and is only diagnosable after birth through histological placenta examination, it is hard to treat, especially where the mother is affected by asymptomatic malaria in pregnancy. Thus, effective diagnostics and adjunctive interventions that may improve pregnancy outcomes during placental malaria are urgently needed. Studies using mouse models of placental malaria indicate the presence of a fetal–maternal innate immune response ‘conflict’ at the placental fetal–maternal interface. In this ‘conflict’, the fetus is thought to respond to the adverse impact of maternal pro-inflammatory immune response to placental malaria by upregulating its own innate immune response on the fetal side of the fetal–maternal interface, which has been reported to improve pregnancy outcomes during placental malaria. However, similar counteractivity between maternal immune responses to placental malaria and defensive immune responses by the fetus at the placenta fetal–maternal interface has not been observed in human placental malaria. In our study, we are using bio-banked human placental tissues from donors living in a malaria-endemic region of Kenya to investigate whether fetal–maternal innate immune ‘conflict’ occurs in response to human placental malaria and if it can be targeted therapeutically for better pregnancy outcomes. Analysis of the data underlying our placental biobank indicate that when compared with controls without known history of malaria during pregnancy, cases of malaria infection during pregnancy have lower birthweight, lower placental weight, and lower birthweight–placental weight ratio, indicating that malaria in pregnancy caused poorer pregnancy outcomes and suggesting the presence of placental malaria. Using histological analysis for the presence of placental malaria (indicated by presence of infected erythrocytes in the placental intervillous spaces and hemozoin deposition in the placenta) we have examined the placental biobank samples and identified placental malaria positive and placental malaria negative samples for downstream characterization.
Our preliminary findings indicate that human placental malaria is associated with an upregulation of TLR4 on the maternal side of the placenta, which is accompanied by strong TLR4 (but not TLR9) upregulation on the fetal side, suggesting that the fetal side of the placenta mounts an innate counter response to placental malaria on the maternal side. Moreover, using immunohistochemical analysis, we have observed that placental malaria might drive oxidative damage as revealed by a marked increase in the levels of the DNA oxidative damage marker, 8-Oxo-7,8-dihydro-2'-deoxyguanosine, in placental malaria positive samples when compared with placental malaria-free controls. We are further investigating the mechanisms by which these observations affect placental malaria outcomes as well as their implications for placental malaria diagnosis and treatment.

This project (TMA2019CDF-2736) has received funding from the EDCTP2 programme supported by the European Union and Novartis Global Health Basel Switzerland’.