To Explore Potential Natural Inhibitors of Cysteine Proteases to Combat Human African Trypanosomiasis and Chagas Disease.

BACKGROUND: Human African Trypanosomiasis (HAT), also known as sleeping sickness, and Chagas disease are neglected tropical diseases caused by Trypanosoma brucei and Trypanosoma cruzi, respectively. These diseases present significant challenges in treatment due to the toxicity, low efficacy, and drug-resistant strains associated with current therapies. INTRODUCTION: Cysteine proteases play vital roles in the life cycles of these parasites, making them potential targets for therapeutic intervention. Natural inhibitors sourced from plants, marine organisms, and microorganisms show promise for developing novel therapies. METHODS: This review surveys the potential of natural inhibitors as therapeutic agents against HAT and Chagas disease. It compiles PubMed and PubChem information from various studies to provide an overview of their activities and characteristics, including their ability to inhibit cysteine proteases, modulate the host immune response, and interfere with other parasite proteins. RESULTS: Several natural inhibitors, such as berberine, curcumin, and tannins, have been identified and characterized. These inhibitors have demonstrated encouraging outcomes in both in vitro and in vivo experiments, indicating their potential as therapeutic agents for HAT and Chagas disease. CONCLUSION: Natural inhibitors of cysteine proteases offer a promising avenue for developing novel therapies against HAT and Chagas disease. Further research is needed to identify additional natural inhibitors and optimize their efficacy and safety for human use. The significance of this study lies in its potential to contribute to the discovery of effective, safe, and affordable treatments for these neglected tropical diseases.

Trypanosoma cruzi reprograms mitochondrial metabolism within the anterior midgut of its vector Rhodnius prolixus during the early stages of infection.

BACKGROUND: Trypanosoma cruzi is transmitted to humans by hematophagous bugs belonging to the Triatominae subfamily. Its intra-vectorial cycle is complex and occurs exclusively in the insect's midgut. Dissecting the elements involved in the cross-talk between the parasite and its vector within the digestive tract should provide novel targets for interrupting the parasitic life cycle and affecting vectorial competence. These interactions are shaped by the strategies that parasites use to infect and exploit their hosts, and the host's responses that are designed to detect and eliminate parasites. The objective of the current study is to characterize the impact of T. cruzi establishment within its vector on the dynamics of its midgut. METHODS: In this study, we evaluated the impact of T. cruzi infection on protein expression within the anterior midgut of the model insect Rhodnius prolixus at 6 and 24 h post-infection (hpi) using high-throughput quantitative proteomics. RESULTS: Shortly after its ingestion, the parasite modulates the proteome of the digestive epithelium by upregulating 218 proteins and negatively affecting the expression of 11 proteins involved in a wide array of cellular functions, many of which are pivotal due to their instrumental roles in cellular metabolism and homeostasis. This swift response underscores the intricate manipulation of the vector's cellular machinery by the parasite. Moreover, a more in-depth analysis of proteins immediately induced by the parasite reveals a pronounced predominance of mitochondrial proteins, thereby altering the sub-proteomic landscape of this organelle. This includes various complexes of the respiratory chain involved in ATP generation. In addition to mitochondrial metabolic dysregulation, a significant number of detoxifying proteins, such as antioxidant enzymes and P450 cytochromes, were immediately induced by the parasite, highlighting a stress response. CONCLUSIONS: This study is the first to illustrate the response of the digestive epithelium upon contact with T. cruzi, as well as the alteration of mitochondrial sub-proteome by the parasite. This manipulation of the vector's physiology is attributable to the cascade activation of a signaling pathway by the parasite. Understanding the elements of this response, as well as its triggers, could be the foundation for innovative strategies to control the transmission of American trypanosomiasis, such as the development of targeted interventions aimed at disrupting parasite proliferation and transmission within the triatomine vector.

Oral Pyronaridine Tetraphosphate Reduces Tissue Presence of Parasites in a Mouse Model of Chagas Disease.

The eukaryotic parasite Trypanosoma cruzi (T. cruzi) is responsible for Chagas disease, which results in heart failure in patients. The disease is more common in Latin America, and is an emerging infection with The Centers for Disease Control estimating that greater than 300,000 people are currently infected in the United States. This disease has also spread from South and Central America, where it is endemic to many other countries, including Australia, Japan, and Spain. Current therapy for Chagas disease is inadequate due to limited efficacy in the indeterminate and chronic phases of the disease, in addition to the adverse effects from nifurtimox and benznidazole, which are nitro-containing drugs used for therapy. There is a clear need for new therapies for the Chagas disease. Using a computational machine learning approach, we have previously shown that the antimalarial pyronaridine tetraphosphate is active against T. cruzi Brazil-luc in vitro against parasites infecting a myoblast cell line and is also active in vivo in an acute mouse model of Chagas disease when dosed i.p. We now further evaluated oral pyronaridine as a monotherapy to determine the minimum effective dose to treat acute and chronic models of Chagas disease. Our results for T. cruzi Brazil-luc demonstrated daily oral dosing with pyronaridine from 150 to 600 mg/kg resulted in statistically significant inhibition in the 7 day acute mouse model. Combination therapy with daily dosing of benznidazole and pyronaridine in the acute infection model demonstrated that 300 mg/kg pyronaridine could return statistically significant antiparasitic activity to a subtherapetic 10 mg/kg benznidazole. In contrast, pyronaridine as monotherapy or combined with benznidazole lacked efficacy in the chronic mouse model, whereas 100 mg/kg benznidazole alone demonstrated undetectable parasites in the heart of mice. Pyronaridine requires further assessment in other chronic models to identify if it can be used beyond the acute stage of T. cruzi infection.

Phlebotomine sand fly (Diptera: Psychodidae) fauna, blood meal source, and detection of Leishmania (Kinetoplastida: Trypanosomatidae) DNA in the Gurupi Biological Reserve, Eastern Amazon, Brazil.

This study was conducted in the Gurupi Biological Reserve (REBIO-Gurupi), the largest area of Amazon rainforest in Maranhão State, Brazil. The objectives were to survey the sand fly (Diptera: Psychodidae) fauna of REBIO-Gurupi, identify blood meal sources, and investigate the presence of Leishmania (Ross, 1903) (Kinetoplastida: Trypanosomatidae) DNA. Individuals were collected using Centers for Disease Control (CDC) light traps and black and white Shannon traps in May and Jun 2022 and Jan 2023. DNA was extracted from female sand flies and subjected to amplification and sequencing of cytochrome b molecular marker (CYTB) for identification of blood meal sources and the first internal transcribed spacer (ITS-1) of ribosomal DNA for Leishmania detection. A total of 514 sand flies individuals were sampled, of which 93 were identified at the genus or series level (9 taxa) and 421 were identified at the species level (24 taxa). Psychodopygus davisi (Root, 1934) (41.1%), Nyssomyia antunesi (Coutinho, 1939) (10.3%), and Psychodopygus (Mangabeira, 1941) Chagasi Series Barretto, 1962 (9.7%) were the most frequently collected. Human (Homo sapiens, Primates, Hominidae) and tapir (Tapirus terrestris, Perissodactyla, Tapiridae) DNA was detected in 10 female sand flies. Leishmania (Leishmania) infantum Cunha and Chagas, 1937 DNA was detected in 2 specimens of Ps. davisi. Given the presence of vectors of Leishmania in REBIO-Gurupi, it is imperative to conduct more comprehensive studies on the interactions among sand flies, Leishmania, and pathogen reservoirs in the area.

Prevalence analysis of Chagas disease by age group in an endemic region of Brazil: possible scenario of active vectorial transmission.

Objectives: Chagas disease (CD) is an infectious disease that predominantly affects poor and vulnerable populations. The last estimate conducted by the World Health Organization in Latin America regarding the prevalence of CD occurred more than 10 years ago. However, there is a scarcity of data assessing the magnitude of CD in populations residing in considered high-risk regions. Therefore, this study aimed to assess the seroprevalence of CD in an endemic region in Northern Minas Gerais through serologic screening. Methods: This is a prevalence study conducted in the municipalities of Catuti, Mato Verde, Mirabela, Montes Azul, and São Francisco, Minas Gerais, Brazil. Data collection occurred between December 2021 and December 2022, involving a questionnaire with closed-ended questions. The variables analyzed included serologic test results, stratified age groups, health indicators, and housing conditions. Results: Of the 2978 participants, 272 individuals (9.1%) tested positive for CD serology. In the age group of 4 to 14 years, 15 to 49 years, and 50 years or older, the prevalence of positive serology was 0.8% (95% confidence interval [CI] 0.16-1.43), 5.5% (95% CI 4.20-6.83), and 18.8% (95% CI 16.48-21.11), respectively. Among the participating municipalities, Mato Verde had the highest prevalence of positive serology for CD (17%). For participants aged 4 to 14 years with positive serology for CD, first-degree relatives were invited to undergo serologic testing. It was possible to collect samples from relatives of all participants in this age group. However, none of the relatives tested positive. Conclusion: This study identified a 9.1% prevalence of individuals affected by CD who were unaware of their condition. In addition, having infected children in the 4 to 14 age group with mothers with negative serology would rule out congenital transmission of the disease.

Climate change and Trypanosoma cruzi transmission in North and central America.

Trypanosoma cruzi is a protozoan parasite that causes Chagas disease in humans. Transmission of T cruzi by triatomine vectors is dependent on diverse environmental and socioeconomic factors. Climate change, which is disrupting patterns of human habitation and land use, can affect the epidemiology of Chagas disease by influencing the distribution of vector and host species. We conducted a review using triatomine distribution as a proxy for T cruzi transmission in North America (Canada, Mexico, and the USA) and central America (Belize, Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua, and Panama) and investigated the association of T cruzi transmission with climate change, identifying 12 relevant studies. Most studies (n=9) modelled the effect of the scenario of climate change on the distribution of relevant vector species and found that global warming could sometimes favour and sometimes hinder triatomine distribution. There is a need for more research in parasite biology and social sciences to further understand how climate change and socioeconomic factors can affect the epidemiology of this neglected tropical disease.

A Rhodnius prolixus catalytically inactive Calpain protease patterns the insect embryonic dorsal-ventral axis.

The calcium dependent Calpain proteases are modulatory enzymes with important roles in cell cycle control, development and immunity. In the fly model Drosophila melanogaster Calpain A cleaves Cactus/IkappaB and consequently modifies Toll signals during embryonic dorsal-ventral (DV) patterning. Here we explore the role of Calpains in the hemiptera Rhodnius prolixus, an intermediate germband insect where the Bone Morphogenetic Protein (BMP) instead of the Toll pathway plays a major role in DV patterning. Phylogenetic analysis of Calpains in species ranging from Isoptera to Diptera indicates an increase of Calpain sequences in the R. prolixus genome and other hemimetabolous species. One locus encoding each of the CalpC, CalpD and Calp7 families, and seven Calpain A/B loci are present in the R. prolixus genome. Several predicted R. prolixus Calpains display a unique architecture, such as loss of Calcium-binding EF-hand domains and loss of catalytic residues in the active site CysPc domain, yielding catalytically dead Calpains A/B. Knockdown for one of these inactive Calpains results in embryonic DV patterning defects, with expansion of ventral and lateral gene expression domains and consequent failure of germ band elongation. In conclusion, our results reveal that Calpains may exert a conserved function in insect DV patterning, despite the changing role of the Toll and BMP pathways in defining gene expression territories along the insect DV axis.

Vitamin D treatment distinctly modulates cytokine production by peripheral blood mononuclear cells among patients with chronic cardiac and indeterminate clinical forms of Chagas disease.

INTRODUCTION: Chagas disease is caused by the protozoan Trypanosoma cruzi and is clinically divided into acute and chronic phases. Chronic Chagas cardiomyopathy is the most studied manifestation of the disease. Vitamin D deficiency has been suggested as a risk factor for cardiovascular disease. No studies demonstrate the action of this hormone in the cells of patients with chronic Chagas heart disease. OBJECTIVE: To evaluate the in vitro immunomodulatory effect of vitamin D on peripheral blood mononuclear cells of patients with the different chronic clinical forms of Chagas disease. Evaluating vitamin D's in vitro effect on blood cells by producing cytokines. METHODS: Thirteen patients of the undetermined form (IND), 13 of the mild cardiac form (CARD1) and 14 of the severe cardiac form (CARD2) of Chagas disease, and 12 with idiopathic heart disease (CARDid) were included. The cells obtained from peripheral blood were treated in vitro with vitamin D (1 × 10-7 M) for 24 h and cytokines were dosed in the culture supernatant. RESULTS: Although it was not possible to demonstrate statistically significant differences between the groups studied, our data showed that the cells treated with vitamin D modify (p < .05) the production of interferon-γ (IFN-γ) (decrease in IND), tumor necrosis factor-α (TNF-α) (decreased in CARD1 and CARDid), interleukin (IL)-6 (increased in all groups), and IL-10 (decreased in CARD1, CARD2, and CARDid) when compared to untreated cells. CONCLUSION: In vitro treatment with vitamin D distinctly modulated the production of cytokines by mononuclear cells of peripheral blood among patients with chronic and indeterminate cardiac clinical forms of Chagas disease.

Unraveling the Missing Pieces: Exploring the Gaps in Understanding Chagas Cardiomyopathy.

Chagas cardiomyopathy affects a considerable number of patients infected with the protozoan Trypanosoma cruzi (T. cruzi) and remains one of the most neglected tropical diseases despite being a significant contributor to morbidity and mortality in both endemic regions of Latin America and non-endemic countries like the United States. Since its discovery almost a century ago, knowledge gaps still exist in the mechanisms involved in the pathogenesis of Chagas cardiomyopathy, and numerous challenges exist in its diagnosis and treatment. This article reviews the main pathogenetic mechanisms involved in the progression of Chagas cardiomyopathy, which has been proposed as a result of years of research. It also emphasizes the challenges involved in the diagnosis of the asymptomatic indeterminate phase and has focused on several diagnostic techniques, including echocardiography, electrocardiogram (ECG), magnetic resonance imaging (MRI), and nuclear imaging in diagnosing symptomatic Chagas cardiomyopathy. In this article, we have also provided a brief overview of the current treatment of Chagas cardiomyopathy, which is not etiology-specific but instead derived from the knowledge acquired from the treatment of other cardiomyopathies.

Prevention of congenital chagas disease by trypanocide treatment in women of reproductive age: A meta-analysis of observational studies.

BACKGROUND: Maternal-foetal transmission of Chagas disease (CD) affects newborns worldwide. Although Benznidazole and Nifurtimox therapies are the standard treatments, their use during pregnancy is contra-indicated. The effectiveness of trypanocidal medications in preventing congenital Chagas Disease (cCD) in the offsprings of women diagnosed with CD was highly suggested by other studies. METHODS: We performed a systematic review and meta-analysis of studies evaluating the effectiveness of treatment for CD in women of childbearing age and reporting frequencies of cCD in their children. PubMed, Scopus, Web of Science, Cochrane Library, and LILACS databases were systematically searched. Statistical analysis was performed using Rstudio 4.2 using DerSimonian and Laird random-effects models. Heterogeneity was examined with the Cochran Q test and I2 statistics. A p-value of <0.05 was considered statistically significant. RESULTS: Six studies were included, comprising 744 children, of whom 286 (38.4%) were born from women previously treated with Benznidazole or Nifurtimox, trypanocidal agents. The primary outcome of the proportion of children who were seropositive for cCD, confirmed by serology, was signigicantly lower among women who were previously treated with no congenital transmission registered (OR 0.05; 95% Cl 0.01-0.27; p = 0.000432; I2 = 0%). In women previously treated with trypanocidal drugs, the pooled prevalence of cCD was 0.0% (95% Cl 0-0.91%; I2 = 0%), our meta-analysis confirms the excellent effectiveness of this treatment. The prevalence of adverse events in women previously treated with antitrypanocidal therapies was 14.01% (95% CI 1.87-26.14%; I2 = 80%), Benznidazole had a higher incidence of side effects than Nifurtimox (76% vs 24%). CONCLUSION: The use of trypanocidal therapy in women at reproductive age with CD is an effective strategy for the prevention of cCD, with a complete elimination of congenital transmission of Trypanosoma cruzi in treated vs untreated infected women.

Acute Chagas disease outbreaks in Colombia in 2019.

This study seeks to address the critical knowledge gap surrounding the acute phase of Chagas disease in Colombia, with a specific focus on cases reported in 2019. The acute phase of Chagas disease is a pivotal period for intervention, yet it remains poorly understood, particularly in regions where oral transmission is presumed to be a significant factor. By analyzing these recent cases, our research aims to provide a deeper understanding of the dynamics of Chagas disease during its acute phase in Colombia in 2019. This understanding is essential not only for improving disease management and treatment strategies but also for enhancing public health responses to this neglected tropical disease. In particular, our study highlights the importance of identifying and addressing the unique challenges posed by oral transmission routes, which have been increasingly recognized within Colombia's Chagas disease landscape.

Irrigation, migration and infestation: a case study of Chagas disease vectors and bed bugs in El Pedregal, Peru.

BACKGROUND: The city of El Pedregal grew out of a desert, following an agricultural irrigation project in southern Peru. OBJECTIVES: To describe infestation patterns by triatomines and bed bugs and their relationship to migration and urbanization. METHODS: We conducted door-to-door entomological surveys for triatomines and bed bugs. We assessed spatial clustering of infestations and compared the year of construction of infested to un-infested households. To gain a better understanding of the context surrounding triatomine infestations, we conducted in-depth interviews with residents to explore their migration histories, including previous experiences with infestation. FINDINGS: We inspected 5,164 households for Triatoma infestans (known locally as the Chirimacha); 21 (0.41%) were infested. These were extremely spatially clustered (Ripley's K p-value < 0.001 at various spatial scales). Infested houses were older than controls (Wilcoxon rank-sum: W = 33; p = 0.02). We conducted bed bug specific inspections in 34 households; 23 of these were infested. These were spatially dispersed across El Pedregal, and no difference was observed in construction age between bed bug infested houses and control houses (W = 6.5, p = 0.07). MAIN CONCLUSIONS: The establishment of agribusiness companies in a desert area demanded a permanent work force, leading to the emergence of a new city. Migrant farmers, seeking work opportunities or escaping from adverse climatic events, arrived with few resources, and constructed their houses with precarious materials. T. infestans, a Chagas disease vector, was introduced to the city and colonized houses, but its dispersal was constrained by presence of vacant houses. We discuss how changes in the socioeconomic and agricultural landscape can increase vulnerability to vector-borne illnesses.

Flying to the moon: Impactful accounts of triatomines invasion from the 2nd to the 13th floor of an urban residential building in the municipality of Rio Branco, Acre, Brazil.

BACKGROUND: Vectorial transmission through hematophagous triatomine insects remains the primary mode of Chagas Disease contagion. These insects have become increasingly common in urban environments. Therefore, this study aimed to report an encounter of triatomines with trypanosomatid infection in a vertical residential condominium in Rio Branco, the capital of the state of Acre, in the western Brazilian Amazon. METHODS: Triatomines were collected from residents and sent to the municipality's Entomological Surveillance sector. Trypanosomatid positivity was evaluated using optical microscopy, followed by species and genotype identification using molecular biology techniques. RESULTS: Twenty-five adult triatomine specimens were collected from two of three condominium buildings invading apartments from the 2nd to 13th floors. Six specimens were identified as Rhodnius sp. and 19 as R. montenegrensis. Among these, molecular tests were conducted on seven specimens, with five testing positive for Trypanosoma cruzi, all belonging to genotype TcI. CONCLUSIONS: These findings underscore the need for further studies to better understand the invasive capacity of these insects in these environments and the mechanisms involved in this process.

Cyclodextrin Complexes for the Treatment of Chagas Disease: A Literature Review.

Cyclodextrins are ring-shaped sugars used as additives in medications to improve solubility, stability, and sensory characteristics. Despite being widespread, Chagas disease is neglected because of the limitations of available medications. This study aims to review the compounds used in the formation of inclusion complexes for the treatment of Chagas disease, analyzing the incorporated compounds and advancements in related studies. The databases consulted include Scielo, Scopus, ScienceDirect, PubMed, LILACS, and Embase. The keywords used were "cyclodextrin AND Chagas AND disease" and "cyclodextrin complex against Trypanosoma cruzi". Additionally, a statistical analysis of studies on Chagas disease over the last five years was conducted, highlighting the importance of research in this area. This review focused on articles that emphasize how cyclodextrins can improve the bioavailability, therapeutic action, toxicity, and solubility of medications. Initially, 380 articles were identified with the keyword "cyclodextrin AND Chagas disease"; 356 were excluded for not being directly related to the topic, using the keyword "cyclodextrin complex against Trypanosoma cruzi". Over the last five years, a total of 13,075 studies on Chagas disease treatment were found in our literature analysis. The studies also showed interest in molecules derived from natural products and vegetable oils. Research on cyclodextrins, particularly in the context of Chagas disease treatment, has advanced significantly, with studies highlighting the efficacy of molecules in cyclodextrin complexes and indicating promising advances in disease treatment.

Dissimilar Trypanosoma cruzi genotype-specific serological profile assessed by Chagas-Flow ATE IgG1 upon benznidazole etiological treatment of chronic Chagas disease.

The present study aimed to verify the impact of etiological treatment on the genotype-specific serological diagnosis of chronic Chagas disease patients (CH), using the Chagas-Flow ATE IgG1 methodology. For this purpose, a total of 92 serum samples from CH, categorized as Not Treated (NT, n = 32) and Benznidazole-Treated (Bz-T, n = 60), were tested at Study Baseline and 5Years Follow-up. At Study Baseline, all patients have the diagnosis of Chagas disease confirmed by Chagas-Flow ATE IgG1, using the set of attributes ("antigen/serum dilution/cut-off"; "EVI/250/30%"). The genotype-specific serodiagnosis at Study Baseline demonstrated that 96% of patients (44/46) presented a serological profile compatible with TcII genotype infection. At 5Years Follow-up monitoring, NT and Bz-T presented no changes in anti-EVI IgG1 reactivity. However, significant differences were detected in the genotype-specific IgG1 reactivity for Bz-T. The most outstanding shift comprised the anti-amastigote TcVI/(AVI), anti-amastigote TcII/(AII) and anti-epimastigote TcVI/(EVI) reactivities. Regardless no changes in the genotype-specific serology of NT (TcI = 6%; TcII = 94%), distinct T. cruzi genotype-specific sero-classification was detected for Bz-T samples at 5Years Follow-up (TcII = 100%) as compared to Baseline (TcII = 97%; TcVI = 3%). The anti-trypomastigote TcI/(TI) was the attribute accountable for the change in genotype-specific sero-classification. In conclusion, our findings of dissimilar T. cruzi genotype-specific serology upon Bz-treatment re-emphasize the relevance of accomplishing the genotype-specific serodiagnosis during clinical pos-therapeutic management of chronic Chagas disease patients.

Exercise Training Reduces Inflammation and Fibrosis and Preserves Myocardial Function and Perfusion in a Model of Chronic Chagas Cardiomyopathy. / Treinamento Físico Reduz a Inflamação e a Fibrose e Preserva a Função e a Perfusão Miocárdica em um Modelo de Cardiomiopatia Chagásica Crônica.

BACKGROUND: Chronic Chagas cardiomyopathy (CCC) is caused by an inflammatory process induced by Trypanosoma cruzi, which leads to myocarditis with reactive and reparative fibrosis. CCC progresses with myocardial perfusion abnormalities and histopathological events that affect cardiorespiratory fitness (CRF). OBJECTIVES: We evaluated the effects of aerobic physical training (APT) on myocardial perfusion and on morphological and functional impairments related with inflammation and fibrosis in Syrian hamsters with CCC. As a secondary objective, we analyzed the cross-sectional areas of the skeletal muscle. METHODS: Hamsters with CCC and their respective controls were divided into four groups: CCC sedentary, CCC-APT, sedentary control and APT control. Seven months after infection, the animals underwent echocardiography, myocardial perfusion scintigraphy and cardiopulmonary exercise testing. Moderate-intensity APT was performed for fifty minutes, five times a week, for eight weeks. Subsequently, the animals were reassessed. Histopathological analysis was conducted after the above-mentioned procedures. The level of significance was set at 5% in all analyses (p<0.05). RESULTS: CCC sedentary animals presented worse myocardial perfusion defects (MPD) over time, reduced left ventricle ejection fraction (LVEF) and showed more inflammation and fibrosis when compared to other groups (mixed ANOVA analysis). Conversely, APT was able to mitigate the progression of MPD, ameliorate inflammation and fibrosis and improve CRF efficiency in CCC-APT animals. CONCLUSIONS: Our study demonstrated that APT ameliorated cardiac dysfunction, MPD, and reduced inflammation and fibrosis in CCC hamster models. Additionally, CCC-SED animals presented skeletal muscle atrophy while CCC-APT animals showed preserved skeletal muscle CSA. Understanding APT's effects on CCC's pathophysiological dimensions is crucial for future research and therapeutic interventions.

FUNDAMENTO: A Cardiomiopatia Chagásica Crônica (CCC) é causada por um processo inflamatório induzido pelo Trypanosoma cruzi, que leva à miocardite com fibrose reativa e reparativa. A CCC progride com alterações de perfusão miocárdica e eventos histopatológicos que afetam a Aptidão Cardiorrespiratória (ACR). OBJETIVOS: Avaliamos os efeitos do Treinamento Físico Aeróbico (TFA) na perfusão miocárdica e nos comprometimentos morfológicos e funcionais relacionados à inflamação e fibrose em hamsters sírios com CCC. Como objetivo secundário, analisamos as áreas de secção transversa do músculo esquelético. MÉTODOS: Hamsters com CCC e seus respectivos controles foram divididos em quatro grupos: CCC sedentário, CCC-TFA, controle sedentário e controle TFA. Sete meses após a infecção, os animais foram submetidos à ecocardiografia, à cintilografia de perfusão miocárdica e ao teste de esforço cardiopulmonar. TFA de intensidade moderada foi realizado durante cinquenta minutos, cinco vezes por semana, por oito semanas. Posteriormente, os animais foram reavaliados. A análise histopatológica foi realizada após os procedimentos acima mencionados. O nível de significância foi estabelecido em 5% em todas as análises (p<0,05). RESULTADOS: Animais com CCC sedentários apresentaram piores Defeitos de Perfusão Miocárdica (DPM) ao longo do tempo, Fração de Ejeção do Ventrículo Esquerdo (FEVE) reduzida, e apresentaram mais inflamação e fibrose quando comparados aos demais grupos (análise ANOVA mista). Por outro lado, o TFA foi capaz de mitigar a progressão do DPM, atenuar a inflamação e a fibrose e melhorar a eficiência da ACR em animais CCC-TFA. CONCLUSÃO: Nosso estudo demonstrou que o TFA melhorou a disfunção cardíaca, DPM e reduziu a inflamação e a fibrose em modelos de hamster com CCC. Além disso, os animais CCC-SED apresentaram atrofia do músculo esquelético, enquanto os animais CCC-TFA apresentaram a AST do músculo esquelético preservada. Compreender os efeitos da TFA nas dimensões fisiopatológicas da CCC é crucial para futuras pesquisas e intervenções terapêuticas.

Triatomine (Hemiptera: Reduviidae) populations and Trypanosoma cruzi genotyping in peridomestic and sylvatic environments in the semiarid region of Sergipe, Northeastern, Brazil.

We assessed the diversity of triatomines, the rates of natural infection, and the discrete typing units (DTUs) of Trypanosoma cruzi isolated from them in two municipalities in the state of Sergipe, Brazil. Active searches for triatomines were conducted in the peridomicily and wild enviroments of 10 villages within the two municipalities. Triatomines were taxonomically identified and their feces were extracted using the abdominal compression method. Parasite detection was performed using optical microscopy. For Trypanosoma cruzi genotyping via PCR-FFLB, 151 samples of the subspecies Triatoma brasiliensis macromelasoma and Triatoma brasiliensis were isolated from both municipalities. In total, 505 triatomines were collected, with Triatoma brasiliensis macromelasoma being the most frequent species (58.81 %). Triatoma b. brasiliensis was the only species in both peridomestic and wild environments. Regarding the other species, T. pseudomaculata was found only in the peridomestic environment; and T. b. macromelasoma and Psammolestes tertius were found in the wild environment. Three Discrete Typing Units were identified: TcI (87.51 %) detected in T. b. brasiliensis and T. b. macromelasoma, TcI+TcIII (10.41 %) in T. b. macromelasoma, and TcI+Trypanosoma rangeli (2.08 %) in T. b. macromelasoma. It is concluded that T. b. macromelasoma is the species collected most frequently in the studied region and the one that presents the highest rates of natural infection, highlighting its epidemiological importance for the vectorial transmission of Chagas disease in Sergipe.

RhoprCAPA-2 acts as a gonadotropin regulating reproduction in adult female, Rhodnius prolixus.

CAPA peptides play diverse roles in insects, modulating muscle contraction, regulating fluid balance, and reproduction. In Rhodnius prolixus, a hematophagous insect and a vector for human Chagas disease, three CAPA peptides are encoded by the capability gene, including RhoprCAPA-1, RhoprCAPA-2, and RhoprCAPA-PK-1. RhoprCAPA-2 is an anti-diuretic hormone in R. prolixus. Here, we explore the involvement of RhoprCAPA-2 in reproduction in adult female R. prolixus. Double-label immunohistochemistry reveals co-localization of RhoprCAPA-2-like and the glycoprotein hormone (GPA2/GPB5) subunit GPB5-like immunoreactivity in neurosecretory cells in the mesothoracic ganglionic mass and in their neurohemal sites, suggesting these peptides can be co-released to regulate physiological processes. qPCR analysis reveals changes in transcript expression levels of the RhoprCAPA receptor (CAPAR) in the fat body and reproductive tissues after feeding in adult female R. prolixus. RNA interference-mediated knockdown of CAPAR transcript decreases egg production and reduces hatching rate and survival rate in female R. prolixus. Downregulation of CAPAR decreases vitellogenin RhoprVg1 transcript expression in the fat body and deceases its receptor RhoprVgR transcript level in the ovaries; accompanied by a reduction in vitellogenin content in the fat body and hemolymph. Incubation of fat body and ovaries in vitro with RhoprCAPA-2 increases RhoprVg1 transcript expression in the fat body, vitellogenin content in the fat body culture medium, and increases RhoprVgR transcript in the ovaries. These findings implicate the CAPA signaling pathway in reproduction, with RhoprCAPA-2 acting as a gonadotropin in adult female R. prolixus.