Molecular identification of Trypanosoma cruzi in domestic animals in municipalities of the State of Rio Grande do Norte, Brazil.

Trypanosoma cruzi, the etiologic agent of American trypanosomiasis, is a vector-borne zoonotic parasite which has been little studied regarding its infection in domestic animals. In this study, we evaluated the occurrence of natural infection by T. cruzi in farm animals using molecular markers and phylogenetic analysis in blood clot samples of 60 sheep (Ovis aires), 22 goats (Capra hircus), and 14 horses (Equus caballus) in eight municipalities located in an infection risk area in the state of Rio Grande do Norte (RN), Northeast Region of Brazil. Trypanosoma spp. infection was identified by amplifying the rRNA 18S SSU gene in 48.9% of the samples. The SH022 sample showed 99.8% similarity with the Y strain of T. cruzi in phylogeny, grouped in the DTU II clade. Blood clots of sheep, goats, and horses detected T. cruzi kDNA in 28.3% (17/60), 22.7% (5/22), and 15.4% (2/14) of the samples, respectively. These animals were distributed in the three studied mesoregions throughout the state of RN. The identification of natural infection in domestic animals contributes to expand the epidemiological transmission scenario in an area where T. brasiliensis is the main vector.

Lizards as Silent Hosts of Trypanosoma cruzi.

We assessed 4 lizard species in Chile for Trypanosoma cruzi, the causative agent of Chagas disease, and 1 species for its ability to transmit the protozoan to uninfected kissing bugs. All lizard species were infected, and the tested species was capable of transmitting the protozoan, highlighting their role as T. cruzi reservoirs.

Deaths Related to Chagas Disease and COVID-19 Co-Infection, Brazil, March-December 2020.

We analyzed epidemiologic characteristics and distribution of 492 deaths related to Chagas disease and coronavirus disease (COVID-19) co-infection in Brazil during March‒December 2020. Cumulative co-infected death rates were highest among advanced age groups, persons of Afro-Brazilian ethnicity and with low education levels, and geographically distributed mainly in major Chagas disease‒endemic areas.

Geospatial analysis as a tool to identify target areas for Chagas disease education for healthcare providers.

Chagas Disease (CD) is a neglected zoonotic disease of the Americas. It can be fatal if not diagnosed and treated in its early stages. Using geospatial and sensitivity analysis, this study focuses on understanding how to better allocate resources and educational information to areas in the United States, specifically Texas, that have the potential for increased risk of CD cases and the associated costs of addressing the disease. ICD-9 and 10 inpatient hospital diagnostic codes were used to illustrate the salience of potentially missed CD diagnoses (e.g., cardiomyopathic diagnoses) and where these are occurring with more frequency. Coding software along with GIS and Microsoft Excel 3D mapping were used to generate maps to illustrate where there may be a need for increased statewide surveillance and screening of populations at greater risk for CD. The CD cases reported to the Texas Department of State Healthcare Services (TxDSHS) are not homogenously dispersed throughout the state but rather, reveal that the incidences are in clusters and primarily in urban areas, where there is increased access to physician care, CD research and diagnostic capabilities.

Detection of Trypanosoma cruzi infection by PCR in Canis lupus familiaris and their ectoparasites in Chile.

Chronic Chagas disease affects humans and animals, involving rural and urban inhabitants. Dogs participate in the maintenance and transmission of Trypanosoma cruzi. The objective of this study was to evaluate the presence of T. cruzi in dogs and their ticks and fleas, in a rural area of Central Chile. Trypanosoma cruzi was detected by PCR both in dogs and ectoparasites. From the blood samples obtained, 57% were infected by T. cruzi, 5.4% of the ticks detected were positive, and all fleas were negative. Additionally, we performed electrocardiograms and found supraventricular arrhythmia in 44% of T. cruzi-positive dogs. Nevertheless, their risk for supraventricular arrhythmias was not higher in infected versus noninfected dogs. Considering the detected infection levels, dogs act as T. cruzi hosts in Central Chile, and ticks could be used as an indicator of infection when blood samples are not available. However, at this point, there is no indication that these ticks could pass on the parasite to another host. Periodic ectoparasitic treatment of pets should reduce the chance of vectorial transmission of T. cruzi and improve canine health; however, this is an uncommon practice among rural communities, so governmental programs are encouraged to tackle this problem.

Chronic Chagas Disease-the Potential Role of Reinfections in Cardiomyopathy Pathogenesis.

PURPOSE OF THE REVIEW: Chagas disease is a neglected anthropozoonosis of global importance with significant cardiovascular-associated mortality. This review focuses on the Trypanosoma cruzi reinfections' role in chronic Chagas cardiomyopathy pathogenesis. We discuss and summarize the available data related to pathology, pathogenesis, diagnosis, and treatment of reinfections. RECENT FINDINGS: Reinfections influence the genetic and regional diversity of T. cruzi, tissue tropism, modulation of the host's immune system response, clinical manifestations, the risk for congenital infections, differences in diagnostics performances, response to antiparasitic therapy, and the natural history of the disease. Animal models suggest that reinfections lead to worse outcomes and increased mortality, while other studies showed an association between reinfections and lower parasitemia levels and subsequent infection protection. In some regions, the human risk of reinfections is 14% at 5 years. Evidence has shown that higher anti-T. cruzi antibodies are correlated with an increased rate of cardiomyopathy and death, suggesting that a higher parasite exposure related to reinfections may lead to worse outcomes. Based on the existing literature, reinfections may play a role in developing and exacerbating chronic Chagas cardiomyopathy and are linked to worse outcomes. Control efforts should be redirected to interventions that address structural poverty for the successful and sustainable prevention of Chagas disease.

American trypanosomiasis (Chagas disease) in solid organ transplantation.

This review addresses relevant aspects of Chagas disease in the solid organ transplantation setting. This trypanosomiasis was geographically restricted to America, but migration has turned Chagas disease into a global public health concern. Parasite persistence in chronically infected individuals entails the potential of transmission with organ donation and the potential for reactivation under immunosuppression. Prospective monitoring with real-time PCR or direct methods for detection of parasitemia and treatment of documented episodes of transmission/ reactivation (rather than prophylactic treatment) is the recommended approach for managing patients at risk. Chagas disease is an important cause of terminal cardiomyopathy. Clinical results demonstrate that with adequate monitoring and treatment, patients with Chagas cardiomyopathy benefit from heart transplantation, with long-term results even better than patients who underwent heart transplantation due to other conditions. Kidney and liver (and possibly other solid organs) transplantation can be safely performed in chronically infected patients with adequate management. Chronically infected patients are also suitable for organ donation (with the exception of the heart and intestines). Although reactivations and transmissions are observed, serious clinical disease is rare, and they are usually successfully managed with benznidazole or nifurtimox.

Decoys and Dilution: The Impact of Incompetent Hosts on Prevalence of Chagas Disease.

Biodiversity is commonly believed to reduce risk of vector-borne zoonoses. However, researchers already showed that the effect of biodiversity on disease transmission is not that straightforward. This study focuses on the effect of biodiversity, specifically on the effect of the decoy process (additional hosts distracting vectors from their focal host), on reducing infections of vector-borne diseases in humans. Here, we consider the specific case of Chagas disease and use mathematical population models to observe the impact on human infection of the proximity of chickens, which are incompetent hosts for the parasite but serve as a preferred food source for vectors. We consider three cases as the distance between the two host populations varies: short (when farmers bring chickens inside the home to protect them from predators), intermediate (close enough for vectors with one host to detect the presence of the other host type), and far (separate enclosed buildings such as a home and hen-house). Our analysis shows that the presence of chickens reduces parasite prevalence in humans only at an intermediate distance under the condition that the vector birth rate from feeding on chickens is sufficiently low.

Chagas Cardiomyopathy: An Update of Current Clinical Knowledge and Management: A Scientific Statement From the American Heart Association.

BACKGROUND: Chagas disease, resulting from the protozoan Trypanosoma cruzi, is an important cause of heart failure, stroke, arrhythmia, and sudden death. Traditionally regarded as a tropical disease found only in Central America and South America, Chagas disease now affects at least 300 000 residents of the United States and is growing in prevalence in other traditionally nonendemic areas. Healthcare providers and health systems outside of Latin America need to be equipped to recognize, diagnose, and treat Chagas disease and to prevent further disease transmission. METHODS AND RESULTS: The American Heart Association and the Inter-American Society of Cardiology commissioned this statement to increase global awareness among providers who may encounter patients with Chagas disease outside of traditionally endemic environments. In this document, we summarize the most updated information on diagnosis, screening, and treatment of T cruzi infection, focusing primarily on its cardiovascular aspects. This document also provides quick reference tables, highlighting salient considerations for a patient with suspected or confirmed Chagas disease. CONCLUSIONS: This statement provides a broad summary of current knowledge and practice in the diagnosis and management of Chagas cardiomyopathy. It is our intent that this document will serve to increase the recognition of Chagas cardiomyopathy in low-prevalence areas and to improve care for patients with Chagas heart disease around the world.

Treatment with low doses of aspirin during chronic phase of experimental Chagas' disease increases oesophageal nitrergic neuronal subpopulation in mice.

Patients with Chagas' disease may develop dysfunctions of oesophageal and colonic motility resulting from the degeneration or loss of the myenteric neurons of the enteric nervous system. Studies have shown that the use of aspirin, also known as acetylsalicylic acid (ASA), influences the pathogenesis of the disease. However, this remains controversial. The aim of this study was to evaluate the consequences of treatment with low doses of aspirin during the chronic phase of Chagas' disease on oesophageal function. Twenty male Swiss mice, 60 days of age, were used. The animals were infected with Y strain of Trypanosoma cruzi, injected intraperitoneally. Aspirin was given at a dose of 50 mg/kg to some of the infected animals, from the 55th to 63rd day after inoculation on consecutive days, and from the 65th to 75th day on alternate days. We investigated food passage of time, wall structure and nitrergic neuronal population of the distal oesophagus. Our data revealed that the use of low doses of aspirin in chronic Chagas' disease caused an increase in the number of nitrergic neurons and partially prevented hypertrophy of the oesophagus. In addition, the aspirin administration impeded Chagas' diseases associated changes in intestinal transit time. Thus treatment with aspirin in the chronic phase of Chagas' disease changes the natural history of the disease and raises the possibility of using it as a new therapeutic approach to the treatment of this aspect of Chagas' disease pathology.

Ten years (2004-2014) of Chagas disease surveillance and vector control in Ecuador: successes and challenges.

OBJECTIVE: To describe the current situation of Chagas disease in Ecuador and to evaluate the impact of vector control for the period 2004-2014. METHODS: Since 2004, the Ministry of Public Health has formalized activities for the surveillance and control of Chagas disease and we analyzed here available records. RESULTS: More than 200 000 houses were surveyed, and 2.6% were found to be infested (95% CI: 2.6-2.7), and more than 51 000 houses were sprayed with residual insecticide, with important yearly variations. A total of 915 cases of T. cruzi infection were registered. The Amazon region is emerging as a high priority area, where nearly half of T. cruzi infection cases originate. The costal region and the southern highland valleys remain important high-risk area. Vector control efforts over the past 10 years have been effective in the coastal region, where T. dimidiata predominates, and resulted in important reductions in house infestation indices in many areas, even reaching negligible levels in some parishes. CONCLUSION: Vector efforts need to be sustained and expanded for the elimination of T. dimidiata to be feasible. Novel vector control interventions need to be designed to reduce intrusion by several triatomine species present in the Amazon region and southern Ecuador. Strong political commitment is needed to sustain current achievements and improve the national coverage of these programmes.

Oral multicomponent DNA vaccine delivered by attenuated Salmonella elicited immunoprotection against American trypanosomiasis.

We have reported that attenuated Salmonella (S) carrying plasmids encoding the cysteine protease cruzipain (Cz) protects against Trypanosoma cruzi infection. Here, we determined whether immunoprotection could be improved by the oral coadministration of 3 Salmonella carrying the plasmids that encode the antigens Cz, Tc52, and Tc24. SCz+STc52+STc24-immunized mice presented an increased antibody response against each antigen compared with those in the single antigen-immunized groups, as well as higher trypomastigotes antibody-mediated lyses and cell invasion inhibition compared with controls. SCz+STc52+STc24-immunized and -challenged mice rendered lower parasitemia. Weight loss after infection was detected in all mice except those in the SCz+STc52+STc24 group. Moreover, cardiomyopathy-associated enzyme activity was significantly lower in SCz+STc24+STc52-immunized mice compared with controls. Few or no abnormalities were found in muscle tissues of SCz+STc24+STc52-immunized mice, whereas controls presented with inflammatory foci, necrosis, and amastigote nests. We conclude that a multicomponent approach that targets several invasion and metabolic mechanisms improves protection compared with single-component vaccines.

Mapping the Silent Threat: A Comprehensive Analysis of Chagas Disease Occurrence in Riverside Communities in the Western Amazon.

Chagas disease (CD) is a typical tropical illness caused by Trypanosoma cruzi. The objective of this study was to assess the prevalence of Chagas disease in communities in two states of the Brazilian Amazon. Data collection occurred in July in the Alto Juruá region of Acre and in December in the communities of Humaitá, Amazonas, in 2019. A total of 477 participants were included in the study. In the communities of Alto Juruá, triatomine collections and analyses of T. cruzi infection were also carried out. All confirmed cases were found in the state of Acre, resulting in a total prevalence of 1.67. Of these eight cases, seven underwent ECG, all of which were concluded as normal by the physician team's cardiologists. Seventeen triatomine bugs, all belonging to the Rhodnius genus, were captured. The natural infection rate by T. cruzi was 25% in the Nova Cintra community and 66.67% in the Boca do Moa community (Alto Juruá). This research found that more than 1% of the studied population exhibited positive serological results for Chagas disease in the riverine communities during the study period, representing a small portion of cases among those who have not yet been diagnosed.

Structural investigation of Trypanosoma cruzi Akt-like kinase as drug target against Chagas disease.

According to the World Health Organization, Chagas disease (CD) is the most prevalent poverty-promoting neglected tropical disease. Alarmingly, climate change is accelerating the geographical spreading of CD causative parasite, Trypanosoma cruzi, which additionally increases infection rates. Still, CD treatment remains challenging due to a lack of safe and efficient drugs. In this work, we analyze the viability of T. cruzi Akt-like kinase (TcAkt) as drug target against CD including primary structural and functional information about a parasitic Akt protein. Nuclear Magnetic Resonance derived information in combination with Molecular Dynamics simulations offer detailed insights into structural properties of the pleckstrin homology (PH) domain of TcAkt and its binding to phosphatidylinositol phosphate ligands (PIP). Experimental data combined with Alpha Fold proposes a model for the mechanism of action of TcAkt involving a PIP-induced disruption of the intramolecular interface between the kinase and the PH domain resulting in an open conformation enabling TcAkt kinase activity. Further docking experiments reveal that TcAkt is recognized by human inhibitors PIT-1 and capivasertib, and TcAkt inhibition by UBMC-4 and UBMC-6 is achieved via binding to TcAkt kinase domain. Our in-depth structural analysis of TcAkt reveals potential sites for drug development against CD, located at activity essential regions.

The mlpt smORF gene is essential for digestive physiology and molting during nymphal stages in the kissing bug Rhodnius prolixus.

Chagas disease affects around 8 million people globally, with Latin America bearing approximately 10,000 deaths each year. Combatting the disease relies heavily on vector control methods, necessitating the identification of new targets. Within insect genomes, genes harboring small open reading frames (smORFs - < 100 amino acids) present numerous potential candidates. In our investigation, we elucidate the pivotal role of the archetypal smORF-containing gene, mille-pattes/polished-rice/tarsalless (mlpt/pri/tal), in the post-embryonic development of the kissing bug Rhodnius prolixus. Injection of double-stranded RNA targeting mlpt (dsmlpt) during nymphal stages yields a spectrum of phenotypes hindering post-embryonic growth. Notably, fourth or fifth stage nymphs subjected to dsmlpt do not undergo molting. These dsmlpt nymphs display heightened mRNA levels of JHAMT-like and EPOX-like, enzymes putatively involved in the juvenile hormone (JH) pathway, alongside increased expression of the transcription factor Kr-h1, indicating changes in the hormonal control. Histological examination reveals structural alterations in the hindgut and external cuticle of dsmlpt nymphs compared to control (dsGFP) counterparts. Furthermore, significant changes in the vector's digestive physiology were observed, with elevated hemozoin and glucose levels in the posterior midgut of dsmlpt nymphs. Importantly, dsmlpt nymphs exhibit impaired metacyclogenesis of Trypanosoma cruzi, the causative agent of Chagas disease, underscoring the crucial role of proper gut organization in parasite differentiation. Thus, our findings constitute the first evidence of a smORF-containing gene's regulatory influence on vector physiology, parasitic cycle, and disease transmission.

Trypanosoma Cruzi antibody screening in North Texas client owned dogs.

Despite multiple screening efforts to identify exposures to Trypanosoma cruzi, in dogs across southern USA, no published studies could be found involving client owned dogs in the North Texas Metroplex area. Therefore, a limited screen was conducted for client owned dogs, seeking routine or preventative care, from participating veterinary practices in the greater Dallas-Fort Worth (DFW) Metroplex from 2019 to 2021. Participants, with owner consent, ranged in age, breed, and length of time at recorded residence. Ninety-nine samples were acquired from participating veterinary practices, initially assessed with the Chagas StatPak, and positive samples were confirmed with IFA (indirect fluorescent antibody test) at the Texas Veterinary Medical Diagnostic Lab (TVMDL), College Station, Texas. Six samples were positive with the StatPak and only two were confirmed positive with IFA. Both animals were senior (10 and 8 years) with no owner reports of previous cardiac issues. The results appear reasonable within the context of previous studies and the seropositivity rate of 2% (n = 99) for client owned dogs included in this study are lower than previously reported rates for shelter dogs from the North Texas area.

Narrowing the Relationship between Human CCR5 Gene Polymorphisms and Chagas Disease: Systematic Review and Meta-Analysis.

Our aim was to carry out a qualitative and quantitative synthesis of the influence of CCR5 genetic variants on Chagas disease (CD) through a systematic review. A total of 1197 articles were analyzed, and eleven were included in the review. A meta-analysis was conducted along with principal component analyses (PCAs). The polymorphisms found were analyzed using the SNP2TFBS tool to identify possible variants that influence the interaction with gene binding sites. Eleven studied variants were identified: rs2856758, rs2734648, rs1799987, rs1799988, rs41469351, rs1800023, rs1800024, Δ32/rs333, rs3176763, rs3087253 and rs11575815. The studies analyzed were published between 2001 and 2019, conducted in Argentina, Brazil, Spain, Colombia and Venezuela, and included Argentine, Brazilian, Colombian, Peruvian and Venezuelan patients. Eight polymorphisms were subjected to the meta-analysis, of which six were associated with the development of the cardiac form of CD: rs1799987-G/G and G/A in the dominance model and G/G in the recessiveness model; rs2856758-A/G in the codominance model; rs2734648-T/T and T/G in the dominance model; rs1799988-T/T in both the codominance and recessiveness models; rs1800023-G allele and the G/G genotype in the codominance and recessiveness models, and the G/G and G/A genotypes in the dominance model; and rs1800024-T allele. The PCA analyses were able to indicate the relationships between the alleles and the genotypes of the polymorphisms. The SNP2TFBS tool identified rs1800023 as an influencer of the Spi1 transcription factor (p < 0.05). A correlation was established between the alleles associated with the cardiac form of CD in this review, members of the C haplotype of the gene (HHC-TGTG), and the cardiac form of CD.

First Report of Eratyrus cuspidatus (Hemiptera: Reduviidae) Infected with Trypanosoma cruzi in Peridomestic Environment in Chiapas, Mexico.

Background: Triatomine bugs are natural vectors of Trypanosoma cruzi, which causes Chagas disease or American trypanosomiasis. The role of sylvatic triatomine species as vectors of T. cruzi in Mexico remains to be fully understood. Our research on the epidemiology of Chagas disease in Southeastern Mexico involved sampling triatomines in rural settings. Materials and Methods: A triatomine was collected in a peridomestic environment of a rural dwelling in the state of Chiapas. The triatomine was identified morphologically as an adult female Eratyrus cuspidatus Stal. Results: Microscopic analysis revealed flagellate forms of T. cruzi in the feces of the E. cuspidatus collected. This was confirmed by quantitative polymerase chain reaction. Amplification of the mini-exon gene showed that the T. cruzi infecting E. cuspidatus corresponded to lineage I. Conclusions: This is the first report from Mexico of E. cuspidatus found infected in a human dwelling, which represents an important adaptation process to inhabit human environments.

Trypanosoma cruzi Central Nervous System Infection-Pathogenesis, Clinical Manifestations, Diagnosis, and Treatment.

Purpose of Review: Chagas disease (CD) is a neglected tropical disease from the American continent that commonly causes cardiovascular disease. Some patients develop neurological manifestations. We discuss and summarize the pathogenesis, clinical characteristics, diagnosis, and treatment of the central nervous system manifestations of CD. Recent Findings: Cerebrospinal fluid quantitative polymerase chain reaction tests and next-generation sequencing in tissue samples have facilitated disease diagnosis and follow-up. Novel presentations, including retinitis, are now reported. A new MRI sign called "Bunch of açai berries appearance"-multiple hypointense nodular lesions-has been described recently. Treatment with benznidazole at higher doses and the role of therapeutic drug monitoring need to be further studied in this setting. Summary: A high suspicion index is paramount to diagnosing Chagas' central nervous system involvement. Standardized molecular diagnostics can aid in the initial workup. Future development of new therapeutic drugs is crucial because of the toxicity profile of the currently available medications.