Epidemiology and pathogenesis of maternal-fetal transmission of Trypanosoma cruzi and a case for vaccine development against congenital Chagas disease

Abstract

Trypanos o ma cruzi (T. cruzi or Tc) is the causative agent of Chagas disease (CD). It is common for patients to suffer from non-specific symptoms or be clinically asymptomatic with acute and chronic conditions acquired through various routes of transmission. The expecting women and their fetuses are vulnerable to congenital transmission of Tc. Pregnant women face formidable health challenges because the frontline antiparasitic drugs, benznidazole and nifurtimox, are contraindicated during pregnancy. However, it is worthwhile to highlight that newborns can be cured if they are diagnosed and given treatment in a timely manner. In this review, we discuss the pathogenesis of maternal-fetal transmission of Tc and provide a justification for the investment in the development of vaccines against congenital CD.

Keywords: Chagas; Congenital; Maternal-fetal transmission; Trypanosoma cruzi; Vaccine.

Figure 1.. Kuschnir classification for the severity of cardiac disease in Chagas patients.

Class 0 and class 1 exhibit seropositive antibodies with normal to minor ECG cardiac alterations. Class 2 and class 3 display cardiac enlargement and the development of apical aneurysm.

Figure 2.. Diagnostic algorithm proposed for identification of T. cruzi infection in newborns in endemic countries.

Abbreviations: PCR – polymerase chain reaction, Tc – T. cruzi, ELISA – enzyme linked immuno-sorbent assay, IHA – indirect hemagglutination assay, IIF – indirect immunofluorescence assay. * Tests for diagnosis of T. cruzi infection in infants can be performed at the time of mandatory vaccination, according to country-specific public health policies.

Figure 3.. Potential routes of maternal-fetal transmission of Trypanosoma cruzi (Tc).

(A) It is proposed that the parasite invades the intervillous space. (B). Alternative transplacental route of vertical transmission through marginal sinus is shown. (C) It is also suggested that infection spreads through and weaken the fetal membranes that can cause premature rupture and early birth. (D) Congenital transmission may also occur via oral route through ingestion of amniotic fluid with circulating forms of T. cruzi.

Figure 4.. Diagrammatic presentation of increasing parasitic invasion due to the denudation of the chorionic villi syncytiotrophoblast.

Tc: Trypanosoma cruzi.

Figure 5.. Current understanding of placental immune responses to T. cruzi.

(A) Extravillous trophoblasts express innate immune receptors, e.g., toll-like receptor 2 (TLR2; purple) and nod-like receptor (NLR; green). (B) Reactive oxygen species (ROS; black hexagon) and reactive nitrogen species (RNS; red star) are released to kill the parasite, but these reactive species can also damage the placental barrier and provide the parasite access to the fetus. (C) Parasite exposure activated the TLR2 innate immune receptor and placental secretion of IL-6 and IL-10. Tc: Trypanosoma cruzi.

Figure 6.. Potential maternal immune responses to T. cruzi.

(6A) The uterine natural killer (uNK) cells differentiate to pro-pregnancy and produce pregnancy-promoting cytokines that regulate and support placental development. (6B) In decidua, macrophages of M1 and M2 phenotypes are involved in inflammatory responses capable of killing the parasite and tissue renewal and repair critical for normal pregnancy, respectively. Tc: Trypanosoma cruzi.