Congenital Transmission of Trypanosoma cruzi: A Review About the Interactions Between the Parasite, the Placenta, the Maternal and the Fetal/Neonatal Immune Responses

Abstract

Chagas disease (CD), caused by the protozoan parasite Trypanosoma cruzi, is considered a neglected tropical disease by the World Health Organization. Congenital transmission of CD is an increasingly relevant public health problem. It progressively becomes the main transmission route over others and can occur in both endemic and non-endemic countries. Though most congenitally infected newborns are asymptomatic at birth, they display higher frequencies of prematurity, low birth weight, and lower Apgar scores compared to uninfected ones, and some suffer from severe symptoms. If not diagnosed and treated, infected newborns are at risk of developing disabling and life-threatening chronic pathologies later in life. The success or failure of congenital transmission depends on interactions between the parasite, the placenta, the mother, and the fetus. We review and discuss here the current knowledge about these parameters, including parasite virulence factors such as exovesicles, placental tropism, potential placental defense mechanisms, the placental transcriptome of infected women, gene polymorphism, and the maternal and fetal/neonatal immune responses, that might modulate the risk of T. cruzi congenital transmission.

Keywords: Trypanosoma cruzi; congenital chagas disease; infection; maternal-fetal interactions; placenta.

FIGURE 1

Human placental barrier. The human placenta is classified as a hemochorial chorioallantoic placenta. The placenta is composed of a fetal portion, developed from the chorion frondosum, and a maternal portion, or basal decidua, which originates from the endometrium. The functional units, were the placental barrier is located, are the free-floating chorionic villi formed by the trophoblast, and the villous stroma. Maternal blood surrounds and contacts the trophoblast in the placental intervillous space. The trophoblast is a bi-stratified covering epithelium composed of a superficial non-proliferative syncytiotrophoblast (ST), and a proliferate germinal layer, the cytotrophoblast (CT). The trophoblast is connected to and separated from the villous stroma (VS), the fetal connective tissue, and by a basal lamina. The parasite present in the maternal blood (1), that comes in contact with the trophoblast in the intervillous space (2), must cross the placental barrier in order to reach the fetal capillaries (3), and infect the fetus during transplacental transmission.