Targeting fetal-maternal innate response conflict for better placental malaria outcomes

In malaria-endemic regions of sub-Saharan Africa, expectant mothers are at a heightened risk of infection by P. falciparum, the malaria parasite that causes the most severe form of malaria. Malaria in pregnancy results in placental malaria, whereby P. falciparum hides away (sequestration) in the placenta’s vasculature (intervillous space). Sequestration enables P. falciparum to evade clearance by the mother’s immune system and to persist even after peripheral parasite (P. falciparum in the mother’s blood circulation) has been cleared or is undetectable through microscopic examination. P. falciparum sequestration disrupts normal placenta functions, including the transfer of materials such as nutrients and oxygen from the mother to the fetus and clearance of metabolic waste from the fetus. Consequently, placental malaria results in numerous complications that lead to poor pregnancy outcomes, including low birthweight, preterm delivery, and miscarriage. These poor outcomes have been attributed to maternal pro-inflammatory immune responses to P. falciparum sequestration on the maternal side of the placenta. Because placental malaria is not detectable by conventional means like analysis of maternal peripheral blood by microscopy and is only diagnosable after birth by histologically examining the placenta, it is hard to treat, especially where the mother is affected by asymptomatic malaria in pregnancy. Thus, effective 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 fetal-maternal interface of the placenta. In this ‘conflict’, the fetus is thought to respond to the adverse impact of maternal pro-inflammatory immune responses to placental malaria by upregulating its own innate immune response on the fetal side of the fetal-maternal interface, which has been shown to improve pregnancy outcomes during placental malaria. However, similar conflict between maternal immune responses to placental malaria and defensive immune responses by the fetus at the fetal-maternal interface of the placenta has not been reported in humans.

Project information

Enabling Technologies & Assays
Vulnerable Populations

Nov 2020 — Oct 2023

$170,000

Kenya