Chagas Disease Research Articles

Arrhythmogenic Manifestations of Chagas Disease: Perspectives From the Bench to Bedside

Chagas cardiomyopathy caused by infection with the intracellular parasite Trypanosoma cruzi is the most common and severe expression of human Chagas disease. Heart failure, systemic and pulmonary thromboembolism, arrhythmia, and sudden cardiac death are the principal clinical manifestations of Chagas cardiomyopathy. Ventricular arrhythmias contribute significantly to morbidity and mortality and are the major cause of sudden cardiac death. Significant gaps still exist in the understanding of the pathogenesis mechanisms underlying the arrhythmogenic manifestations of Chagas cardiomyopathy. This article will review the data from experimental studies and translate those findings to draw hypotheses about clinical observations. Human- and animal-based studies at molecular, cellular, tissue, and organ levels suggest 5 main pillars of remodeling caused by the interaction of host and parasite: immunologic, electrical, autonomic, microvascular, and contractile. Integrating these 5 remodeling processes will bring insights into the current knowledge in the field, highlighting some key features for future management of this arrhythmogenic disease.

Mortality risk score for patients with Chagas cardiomyopathy and pacemaker.

Prognosis of Chronic Chagasic Cardiomyopathy (CCC) patients depends on functional and clinical factors. Bradyarrhythmia requiring pacemaker is a common complication. Prognosis of these patients is poorly studied, and mortality risk factors are unknown. We aimed to identify predictors of death and to define a risk score for mortality in a large cohort of CCC patients with pacemaker. It was an observational, unicentric and prospective study. The endpoint was all-cause mortality. Cox regression was used to identify predictors of death and to define a risk score. Bootstrapping method was used to internal score validation. We included 555 patients and after a mean follow-up of 3.7±1.5 years, 100 (18%) deaths occurred. Predictors of death were: right ventricular dysfunction (HR [hazard ratio] 2.24; 95%CI 1.41-3.53; P = 0.001); heart failure class III or IV (HR 2.16; 95% confidence interval [95%CI] 1.16-4.00; P = 0.014); renal disease (HR 2.14; 95%CI 1.24-3.68; P = 0.006); left ventricular end-systolic diameter > 44mm (HR 1.97; 95%CI 1.26-3.05; P = 0.003); atrial fibrillation (HR 1.94; 95%CI 1.25-2.99; P = 0.003) and cardiomegaly on X-ray (HR 1.87; 95%CI 1.10-3.17; P = 0.020). The score identified patients with: low (0-20 points), intermediate (21-30 points) and high risk (>31points). The optimism-corrected C-statistic of the predictive model was 0.751 (95% CI 0.696-0.806). Internal validation with bootstrapping revealed a calibration slope of 0.946 (95% CI 0.920-0.961), reflecting a small degree of over-optimism and C-statistic of 0.746 (95% CI 0.692-0.785). This study identified predictors of mortality in CCC patients with pacemaker defining a simple, validated and specific risk score.

Targeting Trypanothione Metabolism in Trypanosomatids

Infectious diseases caused by trypanosomatids, including African trypanosomiasis (sleeping sickness), Chagas disease, and different forms of leishmaniasis, are Neglected Tropical Diseases affecting millions of people worldwide, mainly in vulnerable territories of tropical and subtropical areas. In general, current treatments against these diseases are old-fashioned, showing adverse effects and loss of efficacy due to misuse or overuse, thus leading to the emergence of resistance. For these reasons, searching for new antitrypanosomatid drugs has become an urgent necessity, and different metabolic pathways have been studied as potential drug targets against these parasites. Considering that trypanosomatids possess a unique redox pathway based on the trypanothione molecule absent in the mammalian host, the key enzymes involved in trypanothione metabolism, trypanothione reductase and trypanothione synthetase, have been studied in detail as druggable targets. In this review, we summarize some of the recent findings on the molecules inhibiting these two essential enzymes for Trypanosoma and Leishmania viability.

The usefulness of patient-reported outcome measures in decision making in Chagas cardiomyopathy: a scoping review.

Chagas cardiomyopathy (ChC) presents many biopsychosocial complexities, highlighting the need to have patient self-report questions. This study demonstrates the scope of the use of patient-reported outcome measures (PROMs) in patients with ChC and highlights the main research gaps. This is a scoping review and the search strategy was performed in the Online Medical Literature Analysis and Retrieval System (MEDLINE), Excerpta Medica database (EMBASE), Accumulated Index of Nursing and Allied Health Literature (CINAHL), Cochrane Central, Latin American Literature and Caribbean in Health Sciences (LILACS) and Diagnostic Test Accuracy (DITA). The search identified 4484 studies and 20 studies met the inclusion criteria. The Short-Form of 36 items (SF-36) had potential prognostic value and the ability to identify systolic dysfunction. The Human Activity Profile was able to screen for functional impairment, and the New York Heart Association showed potential prognostic value. The SF-36 and Minnesota Living with Heart Failure Questionnaire were responsive to interventions. The pharmaceutical care affected adherence to treatment as assessed by the Morisky score and also for SF-36. Despite the increased use of PROMs, there are still a large number of gaps in the literature, and further studies using PROMs are needed.

First Report of Seropositivity to Trypanosoma cruzi in Mexican Afro-Descendants from Guerrero and Oaxaca States

Mexican Afro-descendant is a population poorly studied in many aspects, between them the infectious diseases that they suffer. This population is mainly found in the country’s Pacific (Oaxaca and Guerrero states) and Atlantic (Veracruz) coast. In these regions, a diversity of triatomine vectors of the Chagas disease is found. Also, all the genotypes of Trypanosoma cruzi DTUs have been reported. That is why the present study aimed to study the presence of antibodies against T. cruzi and cardiac pathology associated with the Chagas disease in the Mexican Afro-descendant population of Guerrero and Oaxaca. ELISA, Western blot, and recombinant antigen’s ELISA were used to evaluate the seropositivity of these communities. Furthermore, an electrocardiographic study and evaluation of risk factors associated with T. cruzi infection in the Oaxaca and Guerrero populations were conducted. 26.77% of the analyzed population was positive for two serological tests. These percentages are higher than the previously reported for the mestizo population in similar studies. Electrocardiographic results showed cardiac disorder associated with the Chagas disease in the population. Also, risk factors were identified associated with the men’s activities in the outdoor working areas.

Predictor Variables in the Spread of Chagas Disease in Rural Areas

Over a hundred years ago after the discovery of Chagas disease (CD) in Brazil, the World Health Organization estimates a number of 6 to 7 million people infected by Trypanosoma cruzi worldwide. Therefore, the goal of this work was to identify variables related to the spread of infection by T. cruzi in humans living in rural areas, seeking predictor variables. A systematic review of the literature has been conducted, with a search in the Scopus platform, using the search string “Chagas disease” and “rural”, resulting in 85 valid and analyzed scientific studies (1977 and 2022). Twenty-seven predictor variables have been acquired, and 19 of them have been grouped, such as: socioeconomic and educational, housing, environmental, sanitary, and cultural; and 8 variables related to T. cruzi seropositive individuals. The predictor variables yielded significant results (p-value < 0.05) in 59.5% of the cases (195/328), with a median of 66.7%. In other words, studies relating to 50% of the 27 variables showed significance equal to or greater than 66.7% of the time. The independent variables with the highest proportion of significant data (p-value < 0.05) were Education (87.6%), Intradomicile building (70%), Domestic animals (69.6%), and Triatomines (69.2%) in the households. Some variables reached 100%; however, few articles were found, indicating the need for further research, especially for Sanitation and Culture. It has been concluded that, in the several contexts found, the social vulnerability and lack of information led the individual to living in environments where inhabitability is inadequate, to perform limited work activity and develop habits and behaviors which impair them in an environmental insalubrity situation, favorable to the access of vectors and pathogens of anthropozoonoses such as CD.

Insecticidal activity of fluralaner (Exzolt®) administered to Gallus gallus domesticus against triatomines (Hemiptera, Reduviidae, Triatominae)

BackgroundTriatoma infestans, Triatoma brasiliensis, Triatoma pseudomaculata and Rhodnius prolixus are vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. Chickens serve as an important blood food source for triatomines. This study aimed to assess the insecticidal activity of fluralaner (Exzolt®) administered to chickens against triatomines (R. prolixus, T. infestans, T. brasiliensis and T. pseudomaculata).MethodsTwelve non-breed chickens (Gallus gallus domesticus) were randomized based on weight into three groups: negative control (n = 4); a single dose of 0.5 mg/kg fluralaner (Exzolt®) (n = 4); two doses of 0.5 mg/kg fluralaner (Exzolt®) (n = 4). Nymphs of 3rd, 4th and 5th instars of R. prolixus, T. infestans, T. brasiliensis and T. pseudomaculata (all n = 10) were allowed to feed on chickens before treatment, and at intervals of 1, 7, 14, 21, 28, 35 and 56 days after treatment, with insect mortality determined.ResultsTreatment with two doses of fluralaner showed higher insecticidal efficacy against R. prolixus, T. infestans and T. brasiliensis compared to the single-dose treatment. Similar insecticidal efficacy was observed for T. pseudomaculata for one and two doses of fluralaner. Insecticidal activity of fluralaner (Exzolt®) against triatomine bugs was noted up to 21 and 28 days after treatment with one and two doses of fluralaner, respectively.ConclusionsThe results demonstrate that treatment of chickens with fluralaner (Exzolt®) induces insecticidal activity against triatomines for up to 28 days post-treatment, suggesting its potential use as a control strategy for Chagas disease in endemic areas.Graphical

Trypanosoma cruzi in Bats (Chiroptera; Mammalia) from the Brazilian Atlantic Forest, São Paulo State

The causative agent of Chagas disease is Trypanosoma cruzi, which is widely distributed throughout the South American continent and extends into North America. Its occurrence in bats is poorly described and may impact the disease’s maintenance and epidemiology. The aim of this study was to detect the agent by PCR assays targeting kDNA and nuclear DNA in the organs of 203 urban bats and rural vampire bats from the Brazilian Atlantic Forest, São Paulo state, during the pandemic period from 2020 to 2022. In total, 6 of the 203 bats (2.97%) were positive for T. cruzi. Infection was detected in 2% (2/101) of Desmodus rotundus, 33% (1/3) of Nyctinomops laticaudatus, 25% (1/4) of Artibeus lituratus, 4% (1/24) of Eumops glaucinus and in 2% (1/41) of Molossus molossus. The gene sequences obtained were assessed for quality and deposited in a public repository. Fruit bats were statistically associated with positivity for T. cruzi. To our knowledge, this study detected T. cruzi for the first time in bats from São Paulo state and in N. laticaudatus and E. glaucinus species.

Alternative Approaches for the Treatment of Chagas Disease

AbstractChagas disease (CD), or American trypanosomiasis, caused by the parasitic protozoa Trypanosoma cruzi, is a substantial global health burden. This comprehensive review explored the multifaceted landscape of CD treatment, providing a historical perspective on the development and discontinuation of benznidazole (BNZ) and nifurtimox (NF), the primary medications. Efforts towards a pediatric version of BZN in Brazil address demographic‐specific treatments, while concerns over drug resistance prompt the exploration of alternative medications like Amiodarone, Allopurinol, Posaconazole, Ravuconazole, and Fexinidazole, which were clinically tested as antichagasic drugs. In recent years, some of the synthesized derivative (1,3‐thiazoles, 4‐thiazolidinones, 2‐styrylquinolines, imidazole‐containing nitrophthalazine, and some others) were found to better activity as compared to standard drug. Traditional herbal alternatives (Resveratrol, curcumin, 1,8‐cineole, β‐pinene, and some others) rooted in traditional practices show promise, with various plant extracts exhibiting anti‐parasitic properties. The frontier of nanomedicine unfolds with studies on solid nanomedicines, PLA‐nanoparticles, ZIF‐8, BNZ carriers, and PLGA nanoparticles, showcasing improved drug delivery systems and controlled release mechanisms. The absence of a definitive vaccine accentuates ongoing research in recombinant antigens, peptide‐based vaccines, and nanoparticle formulations, with notable candidates like TcG1, TcG2, TcG4, MASPpep‐KLH, adenovirus vectors, Tc24 protein, and integrin activators. A novel strategy combining a recombinant protein vaccine with low dose BZN treatment presents promising results in a mouse model, emphasizing the urgency for further research and potential advancements in CD therapeutics.

Antitrypanosomal activity of new alkoxyhydroperoxides formed by cycloaddition of ozone into allyl moiety of eugenol

Eugenol, a natural phenylpropanoid found in several plants, was exposed to ozone atmosphere to afford three new alkoxyhydroperoxides and prevised homovanillin. The effect of these compounds against the protozoan parasite Trypanosoma cruzi resulted in EC50 values ranging from 7.4 to 10.5 μM, superior to the standard drug benznidazole (EC50 = 18.7 μM). Based on these results, it is possible to consider these compounds as scaffolds for the development of new drug candidates against Chagas disease.

A recombinant chimeric antigen constructed with B-cell epitopes from Mycobacterium leprae hypothetical proteins is effective for the diagnosis of leprosy

The diagnosis if leprosy is difficult, as it requires clinical expertise and sensitive laboratory tests. In this study, we develop a serological test for leprosy by using bioinformatics tools to identify specific B-cell epitopes from Mycobacterium leprae hypothetical proteins, which were used to construct a recombinant chimeric protein, M1. The synthetic peptides were obtained and showed good reactivity to detect leprosy patients, although the M1 chimera have showed sensitivity (Se) and specificity (Sp) values higher than 90.0% to diagnose both paucibacillary (PB) and multibacillary (MB) leprosy patients, but not those developing tegumentary or visceral leishmaniasis, tuberculosis, Chagas disease, malaria, histoplasmosis and aspergillosis, in ELISA experiments. Using sera from household contacts, values for Se and Sp were 100% and 65.3%, respectively. In conclusion, our proof-of-concept study has generated data that suggest that a new recombinant protein could be developed into a diagnostic antigen for leprosy.

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.

Presence of Trypanosoma cruzi TcI and Trypanosoma dionisii in sylvatic bats from Yucatan, Mexico.

Chagas disease is caused by Trypanosoma cruzi, whose genetic structure is divided into six discrete typing units (DTUs) known as TcI-TcVI. In the Yucatan Peninsula, Mexico, information regarding the DTUs circulating in wild mammals is scarce, while this is important knowledge for our understanding of T. cruzi transmission dynamics. In the current study, we sampled wild mammals in a sylvatic site of the Yucatan Peninsula and assessed their infection with T. cruzi by PCR. Then, for infected mammals, we amplified and sequenced nuclear and mitochondrial T. cruzi genetic markers for DTU identification. In total, we captured 99 mammals belonging to the orders Chiroptera, Rodentia and Didelphimorphia. The prevalence of infection with T. cruzi was 9% (9/99; 95% CI [5, 16]), and we identified TcI in a Jamaican fruit bat, Artibeus jamaicensis. Moreover, we fortuitously identified Trypanosoma dionisii in another Jamaican fruit bat and detected an unidentified Trypanosoma species in a third specimen. While the latter discoveries were not expected because we used primers designed for T. cruzi, this study is the first to report the identification of T. dionisii in a bat from Yucatan, Mexico, adding to a recent first report of T. dionisii in bats from Veracruz, and first report of this Trypanosoma species in Mexico. Further research is needed to enhance our knowledge of T. cruzi DTUs and Trypanosoma diversity circulating in wildlife in Southeastern Mexico.

Health literacy & Chagas disease knowledge: A cross-sectional study in Southern Loja Province, Ecuador

ObjectiveHealth literacy is associated with many patient outcomes. This study sought to determine the association between a person's level of health literacy and their knowledge about Chagas disease. MethodsA cross-sectional survey was conducted with people living in two counties in rural Loja Province, Ecuador who attended a mobile health clinic. The communities in which the study was conducted are at high risk of Chagas disease and have limited access to both health care and educational resources. The Spanish version of Short Assessment for Health Literacy measured health literacy. The Chagas Disease Knowledge questionnaire measured knowledge of Chagas disease. t-tests and correlational analysis were used to assess associations. ResultsOverall 85 people participated in this study. A majority of the respondents were female (64.1%), and a plurality were married (40.7%) and had education less than secondary (40.7%). The average age of the sample was 44.31 ± 18.85. Health literacy levels and Chagas disease knowledge in the communities were low. About half of people had inadequate health literacy. No association between health literacy and Chagas knowledge was found. ConclusionHealth literacy levels and Chagas disease knowledge were not found to be correlated. Explanations for the lack of association may include common causes of inadequate investment in Chagas disease education as well as neglect of health systems in rural Ecuador. Efforts to improve both health literacy and Chagas disease knowledge in poorer, rural areas of Ecuador are needed. InnovationThis is the first study to assess relationships between health literacy and knowledge of Chagas disease in an uninfected population. For novel conditions, relationships between health literacy and disease knowledge should be investigated before communication campaigns are adapted.

Discovery of Novel Inhibitors of Cruzain Cysteine Protease of Trypanosoma cruz.

Chagas disease (CD) is a parasitic disease endemic in several developing countries. According to the World Health Organization, approximately 6-8 million people worldwide are inflicted by CD. The scarcity of new drugs, mainly for the chronic phase, is the main reason for treatment limitation in CD. Therefore, there is an urgent need to discover new targets for which new therapeutical agents could be developed. Cruzain cysteine protease (CCP) is a promising alternative because this enzyme exhibits pleiotropic effects by acting as a virulence factor, modulating host immune cells, and interacting with host cells. This systematic review was conducted to discover new compounds that act as cruzain inhibitors, and their effects in vitro were studied through enzymatic assays and molecular docking. Additionally, the advances and perspectives of these inhibitors are discussed. These findings are expected to contribute to medicinal chemistry in view of the design of new, safe, and efficacious inhibitors against Trypanosoma cruzi CCP detected in the last decade (2013-2022) to provide scaffolds for further optimization, aiming toward the discovery of new drugs.

The mitochondrial uncoupler 2,4-dinitrophenol modulates inflammatory and oxidative responses in Trypanosoma cruzi-induced acute myocarditis in mice

By uncoupling oxidative phosphorylation, 2,4-dinitrophenol (DNP) attenuates reactive oxygen species (ROS) biosynthesis, which are known to aggravate infectious myocarditis in Chagas disease. Thus, the impact of DNP-based chemotherapy on Trypanosoma cruzi-induced acute myocarditis was investigated. C56BL/6 mice uninfected and infected untreated and treated daily with 100 mg/kg benznidazole (Bz, reference drug), 5 and 10 mg/kg DNP by gavage for 11 days after confirmation of T. cruzi infection were investigated. Twenty-four hours ​after the last treatment, the animals were euthanized and the heart was collected for microstructural, immunological and biochemical analyses. T. cruzi inoculation induced systemic inflammation (e.g., cytokines and anti-T. cruzi IgG upregulation), cardiac infection (T. cruzi DNA), oxidative stress, inflammatory infiltrate and microstructural myocardial damage in untreated mice. DNP treatment aggravated heart infection and microstructural damage, which were markedly attenuated by Bz. DNP (10 mg/kg) was also effective in attenuating ROS (total ROS, H2O2 and O2−), nitric oxide (NO), lipid (malondialdehyde - MDA) and protein (protein carbonyl - PCn) oxidation, TNF, IFN-γ, IL-10, and MCP-1/CCL2, anti-T. cruzi IgG, cardiac troponin I levels, as well as inflammatory infiltrate and cardiac damage in T. cruzi-infected mice. Our findings indicate that DNP aggravated heart infection and microstructural cardiomyocytes damage in infected mice. These responses were related to the antioxidant and anti-inflammatory properties of DNP, which favors infection by weakening the pro-oxidant and pro-inflammatory protective mechanisms of the infected host. Conversely, Bz-induced cardioprotective effects combined effective anti-inflammatory and antiparasitic responses, which protect against heart infection, oxidative stress and microstructural damage in Chagas disease.

Trends in imported infections among migrants and travellers to Spain: a decade of analysis through the +Redivi network (2012-2022).

High-speed global travel, increased trade, world population growth, migration, urbanisation and climate change have favoured the emergence and spread of pathogens. We aimed to analyse the evolution of imported infections in Spain during 2012-2022 and the potential impact of some of the abovementioned factors on differential morbidity patterns. In this retrospective study (January/2012 to December/2022), we analysed data collected by the +Redivi network across 25 health centres. The network's standardised database records new cases of imported infections, including patient demographics, travel history, pre-travel advice and diagnostic information. To assess outcome rates over time and potential interactions, we constructed penalised weighted models to reduce the bias related to a low event rate and used weighted logistic regression for morbidity outcomes. We recorded 25 632 episodes, comprising 13 913 migrants, 4047 visiting friends and relatives (VFR) immigrants, 392 VFR travellers and 7280 travellers. Most immigrants came from South America (48.3%), Sub-Saharan Africa (28.5%), North Africa (6.6%), South Central Asia (5.4%) and Central America/Caribbean (5.3%). The most common regions visited by travellers were Sub-Saharan Africa (33.5%), South America (24.5%), Central America/Caribbean (13.5%), Southeast Asia (12%) and South Central Asia (10%). The proportion of diagnoses of malaria, strongyloidiasis and unspecified self-limiting febrile syndrome < 3weeks remained unchanged during the study period. An increased frequency of diagnosis was reported for schistosomiasis, blastocystosis, giardiasis, dengue, diarrhoea, new cases of HIV, latent and pulmonary tuberculosis; a decrease was reported for syphilis, chikungunya fever, Chagas disease and eosinophilia. We detected interactions between time and sex or type of participant across the different diagnoses. Our study underscores the importance of epidemiological data in understanding infectious diseases dynamics among travellers and migrants, emphasising how demographic shifts, migration trends and healthcare policies affect disease profiles. Comprehensive data play an essential role in enhancing public health policies and travel advice.

Apparent absence of Trypanosoma cruzi in Mexican free-tailed bats (Tadarida brasiliensis) from Texas, USA

The Mexican free-tailed bat (Tadarida brasiliensis) is one of the most abundant mammals in North America. Mexican free-tailed bats have a wide geographic range stretching from northern South America to the western United States. Bats are theorized to be the original hosts for Trypanosoma cruzi —the causative agent of Chagas disease— and can serve as a source of infection to triatomine insect vectors that feed upon them. Chagas disease is a neglected tropical disease across the Americas where triatomines are present, including the southern United States, where Texas reports this highest number of locally-acquired human cases. To learn more about the role of bats in the ecology of Chagas disease in Texas, we surveyed a colony of Mexican free-tailed bats from Brazos County, Texas, for T. cruzi using carcasses salvaged after an extreme weather event. A total of 283 Mexican free-tailed bats collected in February 2021 were dissected and DNA from the hearts and kidneys was used for T. cruzi detection via qPCR. None of the bat hearts or kidneys tested positive for T. cruzi; this sample size affords 95% confidence that the true prevalence of T. cruzi in this population does not exceed 1%. Future sampling of multiple bat species as well as migrant and resident colonies of Mexican free-tailed bats across different times of the year over a broader geographic range would be useful in learning more about the role of bats in the ecology of Chagas disease in Texas.

Variety is the spice: the role of morphological variation of Triatoma infestans (Hemiptera, Reduviidae) at a macro-scale§

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi (Chagas, 1909). One of the primary vectors of T. cruzi in South America is Triatoma infestans (Klug, 1834). This triatomine species is distributed across a huge latitudinal gradient, inhabiting domiciliary , peridomiciliary , and wild environments. Its wide geographic distribution provides an excellent opportunity to study the relationships between environmental gradients and intraspecific morphological variation. In this study, we investigated variations in wing size and shape in T. infestans across six ecoregions. We aimed to address the following questions: How do wing size and shape vary on a regional scale, does morphological variation follow specific patterns along an environmental or latitudinal gradient, and what environmental factors might contribute to wing variation? Geometric morphometric methods were applied to the wings of 162 females belonging to 21 T. infestans populations, 13 from Argentina (n = 105), 5 from Bolivia (n = 42), and 3 from Paraguay (n = 15). A comparison of wing centroid size across the 21 populations showed significant differences. Canonical Variate Analysis (CVA) revealed significant differences in wing shape between the populations from Argentina, Bolivia, and Paraguay, although there was a considerable overlap, especially among the Argentinian populations. Well-structured populations were observed for the Bolivian and Paraguayan groups. Two analyses were performed to assess the association between wing size and shape, geographic and climatic variables: multiple linear regression analysis (MRA) for size and Partial Least Squares (PLS) regression for shape. The MRA showed a significant general model fit. Six temperature-related variables, one precipitation-related variable, and the latitude showed significant associations with wing size. The PLS analysis revealed a significant correlation between wing shape with latitude, longitude, temperature-related, and rainfall-related variables. Wing size and shape in T. infestans populations varied across geographic distribution. Our findings demonstrate that geographic and climatic variables significantly influence T. infestans wing morphology.

Revisión sistemática y metanálisis de la mortalidad en la miocardiopatía chagásica crónica frente a otras miocardiopatías: ¿mayor riesgo o ficción?

Introduction and objectives Although multiple studies suggest that chronic Chagas cardiomyopathy (CCC) has higher mortality than other cardiomyopathies, the absence of meta-analyses supporting this perspective limits the possibility of generating robust conclusions. The aim of this study was to systematically evaluate the current evidence on mortality risk in CCC compared with that of other cardiomyopathies.Methods PubMed/Medline and EMBASE were searched for studies comparing mortality risk between patients with CCC and those with other cardiomyopathies, including in the latter nonischemic cardiomyopathy (NICM), ischemic cardiomyopathy, and non-Chagas cardiomyopathy (nonCC). A random-effects meta-analysis was performed to combine the effects of the evaluated studies.Results A total of 37 studies evaluating 17 949 patients were included. Patients with CCC had a significantly higher mortality risk compared with patients with NICM (HR, 2.04; 95%CI, 1.60-2.60; I2, 47%; 8 studies) and non-CC (HR, 2.26; 95%CI, 1.65-3.10; I2, 71%; 11 studies), while no significant association was observed compared with patients with ischemic cardiomyopathy (HR, 1.72; 95%CI, 0.80-3.66; I2, 69%; 4 studies) in the adjusted-measures meta-analysis.Conclusions Patients with CCC have an almost 2-fold increased mortality risk compared with individuals with heart failure secondary to other etiologies. This finding highlights the need for effective public policies and targeted research initiatives to optimally address the challenges of CCC.