Search

Background: A vaccine against Trypanosoma cruzi, the agent of Chagas disease, would be an excellent additional tool for disease control. A recombinant vaccine based on Tc24 and TSA1 parasite antigens was found to be safe and immunogenic in naïve macaques. Methods: We used RNA-sequencing and performed a transcriptomic analysis of PBMC responses to vaccination of naïve macaques after each vaccine dose, to shed light on the immunogenicity of this vaccine and guide the optimization of doses and formulation. We identified differentially expressed genes and pathways and characterized immunoglobulin and T cell receptor repertoires. Results: RNA-sequencing analysis indicated a clear transcriptomic response of PBMCs after three vaccine doses, with the up-regulation of several immune cell activation pathways and a broad non-polarized immune profile. Analysis of the IgG repertoire showed that it had a rapid turnover with novel IgGs produced following each vaccine dose, while the TCR repertoire presented several persisting clones that were expanded after each vaccine dose. Conclusions: These data suggest that three vaccine doses may be needed for optimum immunogenicity and support the further evaluation of the protective efficacy of this vaccine. [ABSTRACT FROM AUTHOR]

Trypanosoma cruzi is a protozoan parasite causing Chagas disease, with a complex life cycle involving different stages in insect vectors and mammalian hosts. Amastigotes are an intracellular form that replicates in the cytoplasm of host cells, and recent studies suggested that dormant forms may be contributing to parasite persistence, suggesting cellular heterogeneity among amastigotes. We investigated here if a transcriptomic approach could identify some heterogeneity in intracellular amastigotes and identify a dormant population. We used gene expression data derived from bulk RNA-sequencing of T. cruzi infection of human fibroblasts for deconvolution using CDSeq, which allows to simultaneously estimate amastigote cell-type proportions and cell-type-specific expression profiles. Six amastigote subpopulations were identified, confirming intracellular amastigotes heterogeneity, and one population presented characteristics of non-replicative dormant parasites, based on replication markers and TcRAD51 expression. Transcriptomic approaches appear to be powerful to understand T. cruzi cell differentiation and expansion of these studies could provide further insight on the role different cell types in parasite persistence and Chagas disease pathogenesis. [ABSTRACT FROM AUTHOR]

Chagas disease is a leading cause of non-ischemic cardiomyopathy in endemic regions of Central and South America. In Belize, Triatoma dimidiata sensu lato has been identified as the predominate taxon but vectorial transmission of Chagas disease is considered to be rare in the country. We recently identified an acute case of vector-borne Chagas disease in the northern region of Belize. Here we present a subsequent investigation of triatomines collected around the case-patient's home. We identified yet undescribed species, closely related to Triatoma huehuetenanguensis vector by molecular systematics methods occurring in the peridomestic environment. The identification of a T. cruzi-positive, novel species of Triatoma in Belize indicates an increased risk of transmission to humans in the region and warrants expanded surveillance and further investigation. [ABSTRACT FROM AUTHOR]

Chagas disease by Trypanosoma cruzi (T. cruzi) infection is a leading cause of myocarditis worldwide. Chagas cardiomyopathy is presented with a wide variety of conduction abnormalities including arrhythmias, first- and second-degree atrioventricular blockade, left ventricular systolic dysfunction and some cases heart failure leading to the death. Currently, there are no effective treatments available against advanced Chagas disease. With the advance in the development of novel therapies, it is important to utilize an animal model that can effectively replicate the diverse stages of Chagas disease, including chronic asymptomatic and symptomatic infection, that are akin to those observed in humans. Therefore, to characterize the cardiac alterations during the evolution of the infection, we evaluated the progression of cardiomyopathy caused by T. cruzi H1 infection in both BALB/c and ICR mouse models by performing electrocardiogram (ECG) studies in unanesthetized mice every month until 210 days post-infection (dpi). In the late chronic phase of infection, we also performed echocardiogram (ECHO) studies to further assess cardiac function. In conclusion, we demonstrated that ICR mice were more susceptible to cardiac alterations compared to BALB/c mice and both mouse strains are suitable experimental models to study chronic T. cruzi infection and novel treatments. [ABSTRACT FROM AUTHOR]

Trypanosoma cruzi-associated megaesophagus was diagnosed in a domestic Louisiana-born llama with no significant travel history. The llama resided in the same rural area of greater New Orleans, Louisiana, where the first human autochthonous case of Chagas disease was identified in the state. Venous blood from the llama tested positive for T. cruzi kinetoplastid DNA by conventional PCR. The cardiac evaluation was unremarkable, while thoracic radiographs revealed generalized megaesophagus. The llama received supportive care, but was ultimately humanely euthanized. The esophagus was severely distended throughout its length on necropsy, and histologic evaluation showed no microscopic changes in esophageal tissue and minimal to mild lymphoplasmacytic inflammation in cardiac tissue. T. cruzi DNA was detected by conventional PCR in the esophagus, small intestine, and blood despite no protozoan organisms being observed in multiple tissue sections examined. This report contributes to the growing body of evidence of local transmission of T. cruzi in the southern United States, and Chagas disease should be considered a differential diagnosis when evaluating llamas and other large animal species for esophageal dysfunction. There is little research describing megaesophagus or Chagas disease in llamas, and this report aims to increase awareness about this zoonotic disease that is becoming more frequently reported in the southern United States. [ABSTRACT FROM AUTHOR]

Objective: To analyse the ecological and social factors involved in infestation of houses by Triatomadimidiata in a rural locality of Veracruz, Mexico, where active transmission of the parasite is occurring. Methods: A survey was applied to the households of the locality to obtain sociodemographic data. In parallel, T. dimidiata insects were collected during one year through community participation. Using PCR, the insects were genotyped, their infection status was assessed, and parasite genotypes infecting the insects were identified. The vector's blood meal sources were identified using a polymerase–heteroduplex chain reaction assay. Results: Seasonal variations in the patterns of infestation by T. dimidiata were observed. An overall infestation rate of 19.46%, a colonisation index of 9.09%, a dispersion rate of 22.15% and a synanthropy index of 80.6% were found. The collected insects were identified as ITS‐2 group 2 insects, and a natural infection with T. cruzi of 54.35% was found. TcI and no‐TcI genotypes of T. cruzi were found in infected insects. Factors such as rain (P = 0.0006) and temperature (P < 0.0001) were associated with infestation. Analysis of the blood meal sources indicated frequent feeding upon humans and mice. Furthermore, house materials and peridomiciles were found to play an important role in the dynamics of infestation. Conclusions: The contribution of this study is important for understanding the epidemiology of Chagas disease in rural areas of the state of Veracruz and will help to the establishment of an entomological surveillance system and implementation of prevention and control measures in accordance with the reality of the area. [ABSTRACT FROM AUTHOR]

• Triatoma dimidiata in Belize fed on at least 13 vertebrate species including humans. • Trypanosoma cruzi TcI and TcIV parasite discrete typing units were detected. • Parasite sequences from Belize differed from sequences from North and South America. • T. dimidiata harbored a diverse bacterial microbiota with ontogenic changes. In Belize, the main vector for Trypanosoma cruzi , the agent of Chagas disease, is Triatoma dimidiata , but transmission cycles and the risk for human infection are unclear. Therefore, the aim of this study was to identify T. dimidiata blood feeding sources and its parasite and microbial diversity, in order to reconstruct T. cruzi parasite transmission ecology in southern Belize. A metabarcoding approach based on deep sequencing of markers was used for bug taxonomy, blood meal sources, T. cruzi genotypes, and microbiota composition. Bugs were collected in 13 villages of Toledo district. Bugs fed on at least 13 species, from domestic hosts such as humans, dogs, cows, and pigs, to synanthropic species such as mice, rats, and opossums, and sylvatic species such as deer, peccary, and kinkajou, in agreement with an opportunistic feeding behavior. Nonetheless, most feeding focused on a few species, including humans. Infection with T. cruzi was detected in 24 of 39 bugs (62%), and the analysis of 242 T. cruzi mini-exon sequences (average 10 ± 5 haplotypes per bug) indicated the presence of TcI and TcIV parasite discrete typing units (DTUs). However, for both DTUs, sequences from Belize mostly clustered apart from sequences from North and South America, suggesting the local differentiation of parasites. T. dimidiata also harbored a diverse bacterial microbiota, with ontogenic changes suggesting microbiota maturation during nymphal development. Together, these results indicate a significant risk for T. cruzi infection in humans. They also highlight the need to better characterize the diversity of T. cruzi strains in the region and its impact on disease epidemiology. [ABSTRACT FROM AUTHOR]