Malaria in Pregnancy: From Placental Infection to Its Abnormal Development and Damage

Abstract

Malaria remains a global health burden with Plasmodium falciparum accounting for the highest mortality and morbidity. Malaria in pregnancy can lead to the development of placental malaria, where P. falciparum-infected erythrocytes adhere to placental receptors, triggering placental inflammation and subsequent damage, causing harm to both mother and her infant. Histopathological studies of P. falciparum-infected placentas revealed various placental abnormalities such as excessive perivillous fibrinoid deposits, breakdown of syncytiotrophoblast integrity, trophoblast basal lamina thickening, increased syncytial knotting, and accumulation of mononuclear immune cells within intervillous spaces. These events in turn, are likely to impair placental development and function, ultimately causing placental insufficiency, intrauterine growth restriction, preterm delivery and low birth weight. Hence, a better understanding of the mechanisms behind placental alterations and damage during placental malaria is needed for the design of effective interventions. In this review, using evidence from human studies and murine models, an integrated view on the potential mechanisms underlying placental pathologies in malaria in pregnancy is provided. The molecular, immunological and metabolic changes in infected placentas that reflect their responses to the parasitic infection and injury are discussed. Finally, potential models that can be used by researchers to improve our understanding on the pathogenesis of malaria in pregnancy and placental pathologies are presented.

Vaccination during pregnancy: A golden opportunity to embrace

“…Malaria is a significant cause of pregnancy complications. 31 Therefore, malaria vaccines might be relevant for pregnant women living or traveling to endemic regions. Nevertheless, developing a product for pregnant women is complex and is still being explored, targeting the placental role in the infection.…”

First-Trimester Pregnancy: Considerations for Wilderness and Remote Travel

“…14 Malaria is the leading infectious cause of fetal growth restriction worldwide. 15 Patients should be counseled about the risks of malaria during pregnancy and encouraged to take appropriate protection measures, including deferring travel if possible. If they are unable to defer travel, chemoprophylaxis and mosquito avoidance are recommended.…”

Infections and Pregnancy: Effects on Maternal and Child Health

“…Malaria parasites, mainly Plasmodium falciparum and Plasmodium vivax , are other pathogens associated with an elevated risk of pregnancy complications, including fetal growth restriction and preterm birth ( Briand et al., 2016 ; Romero et al., 2021 ). Malaria parasite-infected erythrocytes during pregnancy can adhere to placental receptors and trigger placental inflammation and subsequent damage, causing harm to both mother and her infant ( Chua et al., 2021 ). Emerging evidence suggests that malaria parasite-infected women have significantly higher systemic levels of pro-inflammatory cytokines and chemokines, including TNF-α, IFN-γ, IL-10, which appear to be a key mediators of pregnancy complications ( Nasr et al., 2014 ).…”