Why should we care about congenital Chagas disease?

Chagas is a neglected tropical disease caused by the parasite Trypanosoma cruzi (T. cruzi). When the parasite is passed from an infected mother to her baby during pregnancy it is known as congenital Chagas disease. Congenital Chagas disease has become a significant health problem in both areas where the parasite is common and in places where it is not common due to worldwide travel ¹. Because many people do not know about the disease and there are not enough regulations in place to make sure it gets reported, more than a million women capable of having children have T. cruzi infection ². In the United States, ~43,000 women are living with Chagas disease, and about 22-108 cases of congenital T. cruzi infection occur annually ³. Our mouse model showed that T. cruzi infection in female mice resulted in delayed pregnancy, and the parasite was transmitted to the offspring. Additionally, the infected pregnant females gave birth to pups with lower survival rates, decreased birth weight, and slower growth. Pups delivered by infected mice showed damage to their hearts and brains ⁴.

What did we do and what did we find…

Given that drugs to treat T. cruzi might harm the baby during pregnancy, we proposed and tested a vaccine for women before they become pregnant to protect them from the harmful infection and prevent any damage to the baby ⁵. We discovered that giving the vaccine to mice before they became pregnant or to mice that were not mated did not cause any negative reactions. Our discovery shows that it is safe to give the vaccine before pregnancy. Also, the vaccine and T. cruzi infection activates the spleen to fight the infection, even if the mouse is pregnant. The vaccine was found to decrease heart and skeletal muscle damage and lowered the number of parasites for infected pregnant and infected non-pregnant mice. Moreover, we discovered that the vaccine could change the placenta immune system (T cells) during both pregnancy and infection. While the vaccine was found to increase the parasites in the placenta, it reduced the parasites in the fetus. However, it did not lead to a decrease in fetal infections. The vaccine had good effects on the pregnant mice including placenta weight and decreased placenta damage, when compared to pregnant mice that were infected but not given the vaccine.

Why does it matter?

The objective is to protect the mother and developing children from the parasite. Using this mouse model offers a promising approach for monitoring the long-term health outcomes of newborns exposed to T. cruzi from their infected mothers and evaluating treatments against congenital Chagas disease. After thorough testing in various animal models and clinical trials, we anticipate that immune therapy targeting the parasite in children would be both safe and beneficial. This approach could assist in establishing protective immunity, controlling parasites, and preventing the onset of Chagas disease during adulthood. By considering this vaccine-based approach, we can strive to decrease the impact of congenital Chagas disease and, ultimately, play a part in eliminating it as a public health concern.

References

1          Antinori, S. et al. Chagas disease in Europe: A review for the internist in the globalized world. Eur J Intern Med 43, 6-15 (2017). https://doi.org:10.1016/j.ejim.2017.05.001

2          Buekens, P., Berrueta, M., Harville, E., Mazzoni, A. & Xiong, X. Eliminating congenital syphilis and congenital Chagas disease. Lancet Reg Health Am 12, 100287 (2022). https://doi.org:10.1016/j.lana.2022.100287

3          Irish, A., Whitman, J. D., Clark, E. H., Marcus, R. & Bern, C. Updated Estimates and Mapping for Prevalence of Chagas Disease among Adults, United States. Emerg Infect Dis 28, 1313-1320 (2022). https://doi.org:10.3201/eid2807.212221

4          Rios, L. E., Lokugamage, N. & Garg, N. J. Effects of Acute and Chronic Trypanosoma cruzi Infection on Pregnancy Outcomes in Mice: Parasite Transmission, Mortality, Delayed Growth, and Organ Damage in Pups. Am J Pathol 193, 313-331 (2023). https://doi.org:10.1016/j.ajpath.2022.11.010

5          Meymandi, S., Hernandez, S., Park, S., Sanchez, D. R. & Forsyth, C. Treatment of Chagas Disease in the United States. Curr Treat Options Infect Dis 10, 373-388 (2018). https://doi.org:10.1007/s40506-018-0170-z