RESUMEN
BACKGROUND: Chagas disease can lead to life-threatening cardiac manifestations. Regional factors, including genetic characteristics of circulating Trypanosoma cruzi (T. cruzi), have attracted attention as likely determinants of Chagas disease phenotypic expression and Chagas cardiomyopathy (CCM) progression. Our objective was to elucidate the differential transcriptomic signatures of cardiomyocytes resulting from infection with genetically discrete T. cruzi strains and explore their relationships with CCM pathogenesis and progression. METHODS: HL-1 rodent cardiomyocytes were infected with T. cruzi trypomastigotes of the Colombian, Y, or Tulahuen strain. RNA was serially isolated post-infection for microarray analysis. Enrichment analyses of differentially expressed genes (fold-change ≥ 2 or ≤ 0.5) highlighted over-represented biological pathways. Intracellular levels of reactive oxygen species (ROS) were compared between T. cruzi-infected and non-infected HL-1 cardiomyocytes. RESULTS: We found that oxidative stress-related gene ontology terms (GO terms), 'Hypertrophy model', 'Apoptosis', and 'MAPK signaling' pathways (all with P < 0.01) were upregulated. 'Glutathione and one-carbon metabolism' pathway, and 'Cellular nitrogen compound metabolic process' GO term (all with P < 0.001) were upregulated exclusively in the cardiomyocytes infected with the Colombian/Y strains. Mean intracellular levels of ROS were significantly higher in the T. cruzi-infected cardiomyocytes compared to the non-infected (P < 0.0001). CONCLUSIONS: The upregulation of oxidative stress-related and hypertrophic pathways constitutes the universal hallmarks of the cardiomyocyte response elicited by T. cruzi infection. Nitrogen metabolism upregulation and glutathione metabolism imbalance may implicate a relationship between nitrosative stress and poor oxygen radicals scavenging in the unique pathophysiology of Chagas cardiomyopathy.
RESUMEN
BACKGROUND: Since the late twentieth century, Chagas disease gained global attention to suppress the vector burden as a main control strategy in endemic countries. In Central America, multi-national initiative successfully achieved significant reduction in the estimated disease prevalence as well as elimination of the region's principal vector species at the time in 2012. While the last decade has witnessed significant changes in ecosystem-such as urbanization and replacement of the main vector species-that can possibly affect the vector's habitation and residual transmission, the up-to-date vector burden in the region has not been evaluated thoroughly due to the cessation of active vector surveillance. The aim of this study was to update the risk of vector-borne Trypanosoma cruzi infection in El Salvador, the top Chagas disease-endemic country in Central America. METHODS: A nationwide vector survey was conducted in the domestic environment of El Salvador from September 2018 to November 2020. The selection of the houses for inspection was based on expert purposeful sampling. Infection for T. cruzi was examined by microscopic observation of the insects' feces, followed by a species confirmation using PCR. The data were analyzed using R software version 4.1.3. Proportion estimates with 95% confidence intervals were inferred using the Jeffrey's method provided under the epiR package. RESULTS: A total of 1529 Triatoma dimidiata was captured from 107 houses (infestation rate, 34.4%; 107/311) in all the fourteen departments of the country visited within the period; prevalence of T. cruzi infection was as high as 10% (153/1529). In the country, domestic T. dimidiata infestation was distributed ubiquitously, while T. cruzi infection rates varied across the departments. Five out of fourteen departments showed higher infection rates than the average, suggesting sporadic high-risk areas in the country. CONCLUSIONS: Our comprehensive study revealed substantial T. cruzi infection of T. dimidiata across the country, indicating potential active transmission of the disease. Therefore, strengthened surveillance for both vector and human infection is required to truly eliminate the risk of T. cruzi transmission in Central America.