Amplicon Sequencing Reveals Complex Infection in Infants Congenitally Infected With Trypanosoma Cruzi and Informs the Dynamics of Parasite Transmission

Abstract

Congenital transmission of Trypanosoma cruzi is an important source of new Chagas infections worldwide. The mechanisms of congenital transmission remain poorly understood, but there is evidence that parasite factors are involved. Investigating changes in parasite strain diversity during transmission could provide insight into the parasite factors that influence the process. Here we use amplicon sequencing of a single copy T. cruzi gene to evaluate the diversity of infection in clinical samples from Chagas positive mothers and their infected infants. Several infants and mothers were infected with multiple parasite strains, mostly of the same TcV lineage, and parasite strain diversity was higher in infants than mothers. Two parasite haplotypes were detected exclusively in infant samples, while one haplotype was never found in infants. Together, these data suggest multiple parasites initiate a congenital infection and that parasite factors influence the probability of vertical transmission.

Vaccination with parasite-specific TcTASV proteins combined with recombinant baculovirus as a delivery platform protects against acute and chronic Trypanosoma cruzi infection

“…Data reported by other groups using less virulent strains demonstrated that, while some immunization protocols protected mice from rechallenge, T. cruzi infection alone did not ( Bustamante and Tarleton, 2015 ; Chowdhury et al., 2020 ; Mann et al., 2020 ; Ward et al., 2022 ). The effectiveness of our immunization protocol in protecting against re-challenges is highly relevant because, in the context of natural human infections, re-infections are frequent and associated with the risk of chronic manifestations of the disease ( Monje-Rumi et al., 2015 ; Tomasini et al., 2017 ; Prescilla-Ledezma et al., 2021 ; Olivo Freites et al., 2022 ; Hakim et al., 2023 ). Complementary, after immunosuppression, TcTASV-vaccinated and infected mice quickly recovered from the reactivation of the infection, controlling parasitemia to undetectable levels without mortality, while mortality and extremely high levels of parasitemia were detected in control-vaccinated and infected mice.…”

Chagas Disease Diagnostic Testing in Two Academic Hospitals in New Orleans, Louisiana: A Call to Action

“…It is important to identify mothers with Chagas disease and to identify risk factors for vertical transmission that are associated with increased vertical transmission, such as maternal parasitic load [ 12 ]. There is also recent evidence that there are parasite factors, such as haplotypes, that influence the risk of vertical transmission [ 41 ].…”

New insights into Trypanosoma cruzi genetic diversity, and its influence on parasite biology and clinical outcomes

“…These data substantiate the hypothesis that the results reflect the most prevalent DTU within these regions, given that most DTUs have been discerned in human cases of congenital infection. For example, in Bolivia and Argentina, TcV predominantly constituted the detected DTU, although TcII and TcVI have also been documented ( 278 – 282 ). These genotypes are recurrently linked to vertical transmission across the Southern Cone of America ( 278 , 283 – 286 ).…”

“…Moreover, several studies have identified that mixed T. cruzi infections involving different DTUs or haplotypes within the same DTU are frequently detected ( 281 , 282 , 289 , 290 ). A significant aspect of mixed infections is the detection of genetic profiles in infants that differ from those observed in the mother ( 282 , 290 ).…”

“…Moreover, several studies have identified that mixed T. cruzi infections involving different DTUs or haplotypes within the same DTU are frequently detected ( 281 , 282 , 289 , 290 ). A significant aspect of mixed infections is the detection of genetic profiles in infants that differ from those observed in the mother ( 282 , 290 ). This suggests that the occurrence of polyclonal strains is common, highlighting that the dynamics of the T. cruzi population are profoundly influenced by both the host and the environment.…”