Chagas disease is one of the most important tropical infections in the world and mainly affects poor people. The causative agent is the hemoflagellate protozoan Trypanosoma cruzi, which circulates among insect vectors and mammals throughout the Americas. A large body of research on Chagas disease has shown the complexity of this zoonosis, and controlling it remains a challenge for public health systems. Although knowledge of Chagas disease has advanced greatly, there are still many gaps, and it is necessary to continue generating basic and applied research to create more effective control strategies. The aim of this review is to provide up-to-date information on the components of Chagas disease and highlight current trends in research. We hope that this review will be a starting point for beginners and facilitate the search for more specific information.

Chagas disease, caused by the parasite Trypanosoma cruzi, affects millions of people in South America. The current treatments are limited, have severe side effects, and are only partially effective. Drug repositioning, defined as finding new indications for already approved drugs, has the potential to provide new therapeutic options for Chagas. In this work, we conducted a structure-based drug repositioning approach with over 130,000 3D protein structures to identify drugs that bind therapeutic Chagas targets and thus represent potential new Chagas treatments. The screening yielded over 500 molecules as hits, out of which 38 drugs were prioritized following a rigorous filtering process. About half of the latter were already known to have trypanocidal activity, while the others are novel to Chagas disease. Three of the new drug candidates—ciprofloxacin, naproxen, and folic acid—showed a growth inhibitory activity in the micromolar range when tested ex vivo on T. cruzi trypomastigotes, validating the prediction. We show that our drug repositioning approach is able to pinpoint relevant drug candidates at a fraction of the time and cost of a conventional screening. Furthermore, our results demonstrate the power and potential of structure-based drug repositioning in the context of neglected tropical diseases where the pharmaceutical industry has little financial interest in the development of new drugs.

Theory predicts that parasites can affect and thus drive their hosts’ niche. Testing this prediction is key, especially for vector-borne diseases including Chagas disease. Here, we examined the niche use of seven triatomine species that occur in Mexico, based on whether they are infected or not with Trypanosoma cruzi, the vectors and causative parasites of Chagas disease, respectively. Presence data for seven species of triatomines (Triatoma barberi, T. dimidiata, T. longipennis, T. mazzottii, T. pallidipennis, T. phyllosoma and T. picturata) were used and divided into populations infected and not infected by T. cruzi. Species distribution models were generated with Maxent 3.3.3k. Using distribution models, niche analysis tests of amplitude and distance to centroids were carried out for infected vs non-infected populations within species. Infected populations of bugs of six out of the seven triatomine species showed a reduced ecological space compared to non-infected populations. In all but one case (T. pallidipennis), the niche used by infected populations was close to the niche centroid of its insect host. Trypanosoma cruzi may have selected for a restricted niche amplitude in triatomines, although we are unaware of the underlying reasons. Possibly the fact that T. cruzi infection bears a fitness cost for triatomines is what narrows the niche breadth of the insects. Our results imply that Chagas control programmes should consider whether bugs are infected in models of triatomine distribution.

Background: Relatively little is known about how pathogens transmitted by vector insects are affected by changing temperatures analogous to those occurring in the present global warming scenario. One expectation is that, like their ectothermic vectors, an increase in temperature could reduce their fitness. Here, we have investigated the effect of high temperatures on the abundance ofTrypanosoma cruziparasites during infection in the vectorTriatoma pallidipennis.Methods: We exposedT. pallidipennisnymphs to two strains (Morelos and Chilpancingo) ofT. cruzi. Once infected, the fifth-instar bugs were distributed among three different temperature groups, i.e. 20, 30, and 34 °C, and the resulting parasites were counted when the bugs reached adulthood.Results: The number of parasites increased linearly with time at 20 °C and, to a lesser extent, at 30 °C, especially in the Chilpancingo compared to the Morelos strain. Conversely, at 34 °C, the number of parasites of both strains decreased significantly compared to the other two temperatures.Conclusions: These results suggest negative effects on the abundance ofT. cruziinT. pallidipennisat high temperatures. This is the first evidence of the effect of high temperatures on a pathogenic agent transmitted by an insect vector in the context of global warming. Further tests should be done to determine whether this pattern occurs with other triatomine species andT. cruzistrains.Graphical

A wide variety of mammals are involved in the sylvatic cycle ofTrypanosoma cruzi, the causative agent of Chagas disease. In many areas in Latin America whereT. cruziis endemic, this cycle is poorly known, and its main reservoirs have not been identified. In this study we analyzedT. cruziinfection in bats and other small mammals from an Ecological Reserve in southeastern Mexico. From January through March 2021, we captured wild individuals to extract cardiac and peripheral blood, and infection was detected by PCR of the mini-exon gene. In bats, the prevalence of infection was 16.36%, while in small mammals the prevalence was 28.57%. All of the samples that were positive forT. cruziwere identified as the TCI genotype. Our findings suggest that this zone, situated at the periphery of urban zones might have epidemiological relevance in the sylvatic cycle ofT. cruziand needs to be monitored. The infection of bats in this area is particularly concerning since the flight pattern of this populations overlaps with human settlements. Despite being subject to conservation protections, there continue to be anthropogenic actions that disturb the study area, which could exacerbate risks to public health.

Trypanosoma cruzi is a parasite transmitted by the feces of triatomines. Many triatomine species are found in Mexico, and various T. cruzi variants have been isolated from these species, each showing very different virulence and cell tropism. The isolates were obtained from Meccus phyllosoma specimens in three localities in the state of Oaxaca, Mexico: Tehuantitla, Vixhana, and Guichivere. The virulence of each isolate was assessed by quantifying parasitemia, survival, and histopathologic findings. The lineage of each isolate was identified using the mini-exon gene. The expression of the tssa gene during infection was detected in the heart, esophagus, gastrocnemius, and brain. Our results show that the maximum post-infection parasitemia was higher for the Tehuantitla isolate. On genotyping, all isolates were identified as T. cruzi I. The amastigotes in the heart and gastrocnemius were verified for all isolates, but in the brain only for Tehuantitla and Vixhana. The tssa expression allowed us to detect T. cruzi isolates, for Tehuantitla, predominantly in the heart. For Vixhana, a higher tssa expression was detected in gastrocnemius, and for Guichivere, it was higher in the esophagus. Results show that virulence, tropism, and tssa expression can vary, even when the isolates are derived from the same vector species, in the same region, and at similar altitudes.