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Background: Chagas disease, caused by the parasite Trypanosoma cruzi, is a zoonosis that affects more than seven million people. Current limitations on the diagnosis of the disease hinder the prognosis of patients and the evaluation of treatment efficacy, slowing the development of new therapeutic options. The infection is known to disrupt several host metabolic pathways, providing an opportunity for the identification of biomarkers. Methods: The metabolomic and lipidomic profiles of a cohort of symptomatic and asymptomatic patients with T. cruzi infection and a group of uninfected controls were analysed using liquid chromatography/mass spectrometry. Differences among all groups and changes before and after receiving anti-parasitic treatment across those with T. cruzi infection were explored. Results: Three lipids were found to differentiate between symptomatic and asymptomatic participants: 10-hydroxydecanoic acid and phosphatidylethanolamines PE(18:0/20:4) and PE(18:1/20:4). Additionally, sphinganine, 4-hydroxysphinganine, hexadecasphinganine, and other sphingolipids showed post-treatment abundance similar to that in non-infected controls. Conclusions: These molecules hold promise as potentially useful biomarkers for monitoring disease progression and treatment response in patients with chronic T. cruzi infection. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Chagas disease (CD), triggered by the Trypanosoma cruzi parasite, is originally endemic across Latin America, affecting millions. While cardiac complications are widely recognized, the association between CD and stroke remains underexplored. This systematic review aims to elucidate the relationship between CD and stroke, highlighting the cardioembolic origins of stroke in CD patients and assessing the elevated stroke risk compared to non-infected individuals. Methodology: Adhering to the PRISMA guidelines, we conducted a comprehensive search in PubMed and Scopus databases without date restrictions, including articles in both Spanish and English. This approach enabled the identification and analysis of relevant studies to understand the interplay between CD and stroke risk. Results: Our analysis of 25 selected studies indicates that strokes in CD patients predominantly arise from cardioembolic sources. The data underscore a significant increase in stroke risk among individuals infected with T. cruzi compared to uninfected counterparts. Additionally, CD patients face a higher stroke and mortality risk than those with other heart failure etiologies, irrespective of disease severity. Conclusion: The review establishes CD as a critical contributor to stroke incidence, emphasizing the need for heightened awareness and diagnosis of CD in stroke patients, particularly in regions with high CD prevalence. Recognizing the increased stroke risk associated with T. cruzi infection is crucial for developing targeted educational and preventive strategies in endemic areas. [ABSTRACT FROM AUTHOR]

Objective: To analyse hospital case fatality and mortality related to Chagas disease (CD) in Brazil, 2000–2019. Method: This is a mixed ecological study with spatial and temporal trends, based on national population data from the Brazilian Ministry of Health - hospital admissions (HA) and death certificates (DC). Records with CD as a primary or secondary cause of death in HA and/or as an underlying or associated cause of death in DC were evaluated. Temporal trends were analysed by Joinpoint regression and the spatial distribution of age- and gender-adjusted rates, spatial moving averages, and standardized morbidity ratios. Results: There were a total of 4,376 HA due to CD resulting in death in Brazil, with a hospital case fatality rate of 0.11/100,000 inhabitants. The Southeast region had the highest rate (63.9%, n = 2,796; 0.17/100,000 inhabitants). The general trend for this indicator in Brazil is upwards (average annual percentage change [AAPC] 7.5; 95% confidence interval [CI] 5.3 to 9.9), with increases in the North, Northeast and Southeast regions. During the same period 122,275 deaths from CD were registered in DC, with a mortality rate of 3.14/100,000 inhabitants. The highest risk of CD-related death was found among men (relative risk [RR] 1.27) and Afro-Brazilians (RR 1.63). There was a downward trend in CD mortality in the country (AAPC − 0.7%, 95%CI -0.9 to -0.5), with an increase in the Northeast region (AAPC 1.1%, 95%CI 0.6 to 1.6). Municipalities with a very high Brazilian Deprivation Index tended to show an increase in mortality (AAPC 2.1%, 95%CI 1.6 to 2.7), while the others showed a decrease. Conclusion: Hospital case fatality and mortality due to CD are a relevant public health problem in Brazil. Differences related to gender, ethnicity, and social vulnerability reinforce the need for comprehensive care, and to ensure equity in access to health in the country. Municipalities, states, and regions with indicators that reveal higher morbidity and mortality need to be prioritized. [ABSTRACT FROM AUTHOR]

Background: Chagas disease (CD), a neglected parasitic disease caused by Trypanosoma cruzi, poses a significant health threat in Latin America and has emerged globally because of human migration. Trypanosoma cruzi infects humans and over 100 other mammalian species, including dogs, which are important sentinels for assessing the risk of human infection. Nonetheless, the serodiagnosis of T. cruzi in dogs is still impaired by the absence of commercial tests. In this study, we investigated the diagnostic accuracy of four chimeric recombinant T. cruzi IBMP antigens (IBMP-8.1, IBMP-8.2, IBMP-8.3, and IBMP-8.4) for detecting anti-T. cruzi antibodies in dogs, using latent class analysis (LCA). Methods: We examined 663 canine serum samples, employing indirect ELISA with the chimeric antigens. LCA was utilized to establish a latent variable as a gold standard for T. cruzi infection, revealing distinct response patterns for each antigen. Results: The IBMP (Portuguese acronym for the Molecular Biology Institute of Paraná) antigens achieved area under the ROC curve (AUC) values ranging from 90.9% to 97.3%. The highest sensitivity was attributed to IBMP-8.2 (89.8%), while IBMP-8.1, IBMP-8.3, and IBMP-8.4 achieved 73.5%, 79.6%, and 85.7%, respectively. The highest specificity was observed for IBMP-8.4 (98.6%), followed by IBMP-8.2, IBMP-8.3, and IBMP-8.1 with specificities of 98.3%, 94.4%, and 92.7%, respectively. Predictive values varied according to prevalence, indicating higher effectiveness in endemic settings. Conclusions: Our findings underscore the remarkable diagnostic performance of IBMP-8.2 and IBMP-8.4 for the serodiagnosis of Trypanosoma cruzi in dogs, representing a promising tool for the diagnosis of CD in dogs. These chimeric recombinant antigens may not only enhance CD surveillance strategies but also hold broader implications for public health, contributing to the global fight against this neglected tropical disease. [ABSTRACT FROM AUTHOR]

Background: Triatoma 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). Methods: Twelve 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. Results: Treatment 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. Conclusions: The 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. [ABSTRACT FROM AUTHOR]

Background: Triatoma garciabesi and T. guasayana are considered secondary vectors of Trypanosoma cruzi and frequently invade rural houses in central Argentina. Wing and head structures determine the ability of triatomines to disperse. Environmental changes exert selective pressures on populations of both species, promoting changes in these structures that could have consequences for flight dispersal. The aim of this study was to investigate the relationship between a gradient of anthropization and phenotypic plasticity in flight-related traits. Methods: The research was carried out in Cruz del Eje and Ischilín departments (Córdoba, Argentina) and included 423 individuals of the two species of triatomines. To measure the degree of anthropization, a thematic map was constructed using supervised classification, from which seven landscapes were selected, and nine landscape metrics were extracted and used in a hierarchical analysis. To determine the flight capacity and the invasion of dwellings at different levels of anthropization for both species, entomological indices were calculated. Digital images of the body, head and wings were used to measure linear and geometric morphometric variables related to flight dispersion. One-way ANOVA and canonical variate analysis (CVA) were used to analyze differences in size and shape between levels of anthropization. Procrustes variance of shape was calculated to analyze differences in phenotypic variation in heads and wings. Results: Hierarchical analysis was used to classify the landscapes into three levels of anthropization: high, intermediate and low. The dispersal index for both species yielded similar results across the anthropization gradient. However, in less anthropized landscapes, the density index was higher for T. garciabesi. Additionally, in highly anthropized landscapes, females and males of both species exhibited reduced numbers. Regarding phenotypic changes, the size of body, head and wings of T. garciabesi captured in the most anthropized landscapes was greater than for those captured in less anthropized landscapes. No differences in body size were observed in T. guasayana collected in the different landscapes. However, males from highly anthropized landscapes had smaller heads and wings than those captured in less anthropized landscapes. Both wing and head shapes varied between less and more anthropogenic environments in both species. Conclusions: Results of the study indicate that the flight-dispersal characteristics of T. garciabesi and T. guasayana changed in response to varying degrees of anthropization. [ABSTRACT FROM AUTHOR]

Background: Rhodnius zeledoni was described from a single specimen. Since its description, doubts have arisen regarding the taxonomic status of this species in relation to Rhodnius domesticus. Methods: The present study reviewed and compared R. zeledoni with R. domesticus based on morphological analysis and head geometric morphometrics. Results: Our analysis revealed the absence of distinctive diagnostic characters between the two species at specific levels. Rhodnius zeledoni and R. domesticus show morphological and morphometric similarity, with only minor differences in coloration observed between them. Contrary to previous statements, our analysis showed that R. zeledoni and R. paraensis are not closely related species, not corroborating previous studies with such an assumption. Conclusions: Therefore, we formally propose R. zeledoni as a junior synonym of R. domesticus. [ABSTRACT FROM AUTHOR]

Trypanosoma cruzi is the etiologic agent of Chagas disease. This flagellated protozoan is transmitted to humans as well as different species of domestic and wild animals via vectors from the Reduviidae family (known as "kissing bugs"). Despite the fact that hundreds of species of wild mammals are part of the reservoir system, the morphological changes and clinical manifestations resulting from the pathogenesis of the infection have been largely neglected. The aim of this review is to systematically compile the available information regarding clinicopathological alterations in wild mammals due to natural infection by T. cruzi. Information was obtained from six online bibliographic data search platforms, resulting in the identification of 29 publications that met the inclusion criteria. Mortality was the most common clinical manifestation, cardiac damage was the main finding at necropsy, and lymphoplasmacytic inflammation was the most frequent microscopic injury. Thus, regardless of its role as a reservoir, T. cruzi has the potential to affect the health status of wild mammals, a situation that highlights the need for further research to analyze, measure, and compare its effects at both the individual and population levels. [ABSTRACT FROM AUTHOR]

Background: Chagas disease is a neglected tropical disease (NTD). Cost-effective strategies for large-scale implementation of diagnosis and etiological treatment are urgently needed to comply with NTD control goals. We determined the seroprevalence of Trypanosoma cruzi infection and associated risk factors in a well-defined rural population of Pampa del Indio municipality including creole and indigenous (Qom) households and developed two indices to identify houses harboring infected children. Methods: We serodiagnosed and administered a questionnaire to 1337 residents (48.2% of the listed population) in two sections of the municipality (named Areas II and IV) 6–9 years after deploying sustained vector control interventions. Multiple logistic regression models were used to evaluate the relationship between human infection and a priori selected predictors. Two risk indices were constructed based on environmental and serostatus variables, and we used spatial analysis to test whether households harboring T. cruzi-seropositive children were randomly distributed. Results: The global seroprevalence of T. cruzi infection was 24.8%. Human infection was positively and significantly associated with exposure time to triatomines, the household number of seropositive co-inhabitants, maternal seropositivity for T. cruzi, recent residence at the current house and the presence of suitable walls for triatomine colonization in the domicile. The pre-intervention mean annual force of infection (FOI) was 1.23 per 100 person-years. Creoles from Area IV exhibited the highest seroprevalence and FOI; Qom people from both areas displayed intermediate ones and creoles from Area II the lowest. Three hotspots of infected children were spatially associated with hotspots of triatomine abundance at baseline and persistent house infestation. No child born after vector control interventions was T. cruzi seropositive except for one putative transplacental case. Two simple risk indices (based on self-reported inhabiting an infested house and suitable walls for triatomines or maternal serostatus) identified 97.3–98.6% of the households with at least one T. cruzi-seropositive child. Conclusions: We showed strong heterogeneity in the seroprevalence of T. cruzi infection within and between ethnic groups inhabiting neighboring rural areas. Developed indices can be used for household risk stratification and to improve access of rural residents to serodiagnosis and treatment and may be easily transferred to primary healthcare personnel. [ABSTRACT FROM AUTHOR]

Background: Chagas disease can lead to life-threatening cardiac manifestations. Regional factors, including genetic characteristics of circulating Trypanosoma cruzi (T. cruzi), have attracted attention as likely determinants of Chagas disease phenotypic expression and Chagas cardiomyopathy (CCM) progression. Our objective was to elucidate the differential transcriptomic signatures of cardiomyocytes resulting from infection with genetically discrete T. cruzi strains and explore their relationships with CCM pathogenesis and progression. Methods: HL-1 rodent cardiomyocytes were infected with T. cruzi trypomastigotes of the Colombian, Y, or Tulahuen strain. RNA was serially isolated post-infection for microarray analysis. Enrichment analyses of differentially expressed genes (fold-change ≥ 2 or ≤ 0.5) highlighted over-represented biological pathways. Intracellular levels of reactive oxygen species (ROS) were compared between T. cruzi-infected and non-infected HL-1 cardiomyocytes. Results: We found that oxidative stress-related gene ontology terms (GO terms), 'Hypertrophy model', 'Apoptosis', and 'MAPK signaling' pathways (all with P < 0.01) were upregulated. 'Glutathione and one-carbon metabolism' pathway, and 'Cellular nitrogen compound metabolic process' GO term (all with P < 0.001) were upregulated exclusively in the cardiomyocytes infected with the Colombian/Y strains. Mean intracellular levels of ROS were significantly higher in the T. cruzi-infected cardiomyocytes compared to the non-infected (P < 0.0001). Conclusions: The upregulation of oxidative stress-related and hypertrophic pathways constitutes the universal hallmarks of the cardiomyocyte response elicited by T. cruzi infection. Nitrogen metabolism upregulation and glutathione metabolism imbalance may implicate a relationship between nitrosative stress and poor oxygen radicals scavenging in the unique pathophysiology of Chagas cardiomyopathy. [ABSTRACT FROM AUTHOR]

Research has shown that multidimensional approaches to Chagas disease (CD), integrating its biomedical and psycho-socio-cultural components, are successful in enhancing early access to diagnosis, treatment and sustainable follow-up. For the first time, a consulate was selected for a community-based CD detection campaign. Two different strategies were designed, implemented and compared between 2021 and 2022 at the Consulate General of Bolivia and a reference health facility in Barcelona open to all Bolivians in Catalonia. Strategy 1 consisted in CD awareness-raising activities before referring those interested to the reference facility for infectious disease screening. Strategy 2 offered additional in-situ serological CD screening. Most of the 307 participants were Bolivian women residents in Barcelona. In strategy 1, 73 people (35.8% of those who were offered the test) were screened and 19.2% of them were diagnosed with CD. Additionally, 53,4% completed their vaccination schedules and 28.8% were treated for other parasitic infections (strongyloidiasis, giardiasis, eosinophilia, syphilis). In strategy 2, 103 people were screened in-situ (100% of those who were offered the test) and 13.5% received a CD diagnosis. 21,4% completed their vaccination schedule at the reference health facility and 2,9% were referred for iron deficiency anemia, strongyloidiasis or chronic hepatitis C. The fact that the screening took place in an official workplace of representatives of their own country, together with the presence of community-based participants fueled trust and increased CD understanding. Each of the strategies assessed had different benefits. Opportunities for systematic integration for CD based on community action in consulates may enhance early access to diagnosis, care and disease prevention. [ABSTRACT FROM AUTHOR]

Background: The complexity of the Chagas disease and its phases is impossible to have a unique test for both phases and a lot of different epidemiological scenarios. Currently, serology is the reference standard technique; occasionally, results are inconclusive, and a different diagnostic technique is needed. Some guidelines recommend molecular testing. A systematic review and meta-analysis of available molecular tools/techniques for the diagnosis of Chagas disease was performed to measure their heterogeneity and efficacy in detecting Trypanosoma cruzi infection in blood samples. Methods: A systematic review was conducted up to July 27, 2022, including studies published in international databases. Inclusion and exclusion criteria were defined to select eligible studies. Data were extracted and presented according to PRISMA 2020 guidelines. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). A random-effects model was used to calculate pooled sensitivity, specificity, and diagnostic odds ratio (DOR). Forest plots and a summary of the receiving operating characteristics (SROC) curves displayed the outcomes. Heterogeneity was determined by I2 and Tau2 statistics and P values. Funnel plots and Deek's test were used to assess publication bias. A quantitative meta-analysis of the different outcomes in the two different clinical phases was performed. Results: We identified 858 records and selected 32 papers. Studies pertained to endemic countries and nonendemic areas with adult and paediatric populations. The sample sizes ranged from 17 to 708 patients. There were no concerns regarding the risk of bias and applicability of all included studies. A positive and nonsignificant correlation coefficient (S = 0.020; P = 0.992) was obtained in the set of studies that evaluated diagnostic tests in the acute phase population (ACD). A positive and significant correlation coefficient (S = 0.597; P < 0.000) was obtained in the case of studies performed in the chronic phase population (CCD). This resulted in high heterogeneity between studies, with the master mix origin and guanidine addition representing significant sources. Interpretation/Conclusions and relevance: The results described in this meta-analysis (qualitative and quantitative analyses) do not allow the selection of the optimal protocol of molecular method for the study of Trypanosoma cruzi infection in any of its phases, among other reasons due to the complexity of this infection. Continuous analysis and optimization of the different molecular techniques is crucial to implement this efficient diagnosis in endemic areas. [ABSTRACT FROM AUTHOR]

Community engagement strategies provide tools for sustainable vector-borne disease control. A previous cluster randomized control trial engaged nine intervention communities in seven participatory activities to promote management of the domestic and peri-domestic environment to reduce risk factors for vector-borne Chagas disease. This study aims to assess the adoption of this innovative community-based strategy, which included chickens' management, indoor cleaning practices, and domestic rodent infestation control, using concepts from the Diffusion of Innovations Theory. We used questionnaires and semi-structured interviews to understand perceptions of knowledge gained, intervention adoption level, innovation attributes, and limiting or facilitating factors for adoption. The analysis process focused on five innovation attributes proposed by the Diffusion of Innovations Theory: relative advantage, compatibility, complexity, trialability, and observability. Rodent management was highly adopted by participants, as it had a relative advantage regarding the use of poison and was compatible with local practices. The higher complexity was reduced by offering several types of trapping systems and having practical workshops allowed trialability. Observability was limited because the traps were indoors, but information and traps were shared with neighbors. Chicken management was not as widely adopted due to the higher complexity of the method, and lower compatibility with local practices. Using the concepts proposed by the Diffusion of Innovations Theory helped us to identify the enablers and constraints in the implementation of the Chagas vector control strategy. Based on this experience, community engagement and intersectoral collaboration improve the acceptance and adoption of novel and integrated strategies to improve the prevention and control of neglected diseases. [ABSTRACT FROM AUTHOR]

Background: Triatomines are blood-sucking insects capable of transmitting Trypanosoma cruzi, the parasite that causes Chagas disease in humans. Vectorial transmission entails an infected triatomine feeding on a vertebrate host, release of triatomine infective dejections, and host infection by the entry of parasites through mucous membranes, skin abrasions, or the biting site; therefore, transmission to humans is related to the triatomine–human contact. In this cross-sectional study, we evaluated whether humans were detected in the diet of three sylvatic triatomine species (Mepraia parapatrica, Mepraia spinolai, and Triatoma infestans) present in the semiarid–Mediterranean ecosystem of Chile. Methods: We used triatomines collected from 32 sites across 1100 km, with an overall T. cruzi infection frequency of 47.1% (N = 4287 total specimens) by conventional PCR or qPCR. First, we amplified the vertebrate cytochrome b gene (cytb) from all DNA samples obtained from triatomine intestinal contents. Then, we sequenced cytb-positive PCR products in pools of 10–20 triatomines each, grouped by site. The filtered sequences were grouped into amplicon sequence variants (ASVs) with a minimum abundance of 100 reads. ASVs were identified by selecting the best BLASTn match against the NCBI nucleotide database. Results: Overall, 16 mammal (including human), 14 bird, and seven reptile species were identified in the diet of sylvatic triatomines. Humans were part of the diet of all analyzed triatomine species, and it was detected in 19 sites representing 12.19% of the sequences. Conclusions: Sylvatic triatomine species from Chile feed on a variety of vertebrate species; many of them are detected here for the first time in their diet. Our results highlight that the sylvatic triatomine–human contact is noteworthy. Education must be enforced for local inhabitants, workers, and tourists arriving in endemic areas to avoid or minimize the risk of exposure to Chagas disease vectors. [ABSTRACT FROM AUTHOR]

Background: Chagas disease (CD), caused by the parasite Trypanosoma cruzi, is a serious public health concern in Latin America. Nifurtimox and benznidazole (BZ), the only two drugs currently approved for the treatment of CD, have very low efficacies in the chronic phase of the disease and several toxic side effects. Trypanosoma cruzi strains that are naturally resistant to both drugs have been reported. We performed a comparative transcriptomic analysis of wild-type and BZ-resistant T. cruzi populations using high-throughput RNA sequencing to elucidate the metabolic pathways related to clinical drug resistance and identify promising molecular targets for the development of new drugs for treating CD. Methods: All complementary DNA (cDNA) libraries were constructed from the epimastigote forms of each line, sequenced and analysed using the Prinseq and Trimmomatic tools for the quality analysis, STAR as the aligner for mapping the reads against the reference genome (T. cruzi Dm28c—2018), the Bioconductor package EdgeR for statistical analysis of differential expression and the Python-based library GOATools for the functional enrichment analysis. Results: The analytical pipeline with an adjusted P-value of < 0.05 and fold-change > 1.5 identified 1819 transcripts that were differentially expressed (DE) between wild-type and BZ-resistant T. cruzi populations. Of these, 1522 (83.7%) presented functional annotations and 297 (16.2%) were assigned as hypothetical proteins. In total, 1067 transcripts were upregulated and 752 were downregulated in the BZ-resistant T. cruzi population. Functional enrichment analysis of the DE transcripts identified 10 and 111 functional categories enriched for the up- and downregulated transcripts, respectively. Through functional analysis we identified several biological processes potentially associated with the BZ-resistant phenotype: cellular amino acid metabolic processes, translation, proteolysis, protein phosphorylation, RNA modification, DNA repair, generation of precursor metabolites and energy, oxidation–reduction processes, protein folding, purine nucleotide metabolic processes and lipid biosynthetic processes. Conclusions: The transcriptomic profile of T. cruzi revealed a robust set of genes from different metabolic pathways associated with the BZ-resistant phenotype, proving that T. cruzi resistance mechanisms are multifactorial and complex. Biological processes associated with parasite drug resistance include antioxidant defenses and RNA processing. The identified transcripts, such as ascorbate peroxidase (APX) and iron superoxide dismutase (Fe-SOD), provide important information on the resistant phenotype. These DE transcripts can be further evaluated as molecular targets for new drugs against CD. [ABSTRACT FROM AUTHOR]

Background: Current therapeutic agents, including nifurtimox and benznidazole, are not sufficiently effective in the chronic phase of Trypanosoma cruzi infection and are accompanied by various side effects. In this study, 120 kinds of extracts from medicinal herbs used for Kampo formulations and 94 kinds of compounds isolated from medicinal herbs for Kampo formulations were screened for anti-T. cruzi activity in vitro and in vivo. Methods: As an experimental method, a recombinant protozoan cloned strain expressing luciferase, namely Luc2-Tulahuen, was used in the experiments. The in vitro anti-T. cruzi activity on epimastigote, trypomastigote, and amastigote forms was assessed by measuring luminescence intensity after treatment with the Kampo extracts or compounds. In addition, the cytotoxicity of compounds was tested using mouse and human feeder cell lines. The in vivo anti-T. cruzi activity was measured by a murine acute infection model using intraperitoneal injection of trypomastigotes followed by live bioluminescence imaging. Results: As a result, three protoberberine-type alkaloids, namely coptisine chloride, dehydrocorydaline nitrate, and palmatine chloride, showed strong anti-T. cruzi activities with low cytotoxicity. The IC50 values of these compounds differed depending on the side chain, and the most effective compound, coptisine chloride, showed a significant effect in the acute infection model. Conclusions: For these reasons, coptisine chloride is a hit compound that can be a potential candidate for anti-Chagas disease drugs. In addition, it was expected that there would be room for further improvement by modifying the side chains of the basic skeleton. [ABSTRACT FROM AUTHOR]

Background: Triatoma guasayana is considered an emerging vector of Chagas disease in the Southern Cone of South America. The presence of a triatomine population with brachypterous individuals, in which both wings are reduced, has recently been reported for this species. The aim of the present study was to determine if flight-related traits varied across populations, if these traits could explain differences in flight capacity across populations and if flight-related traits are associated with geographic and/or climatic variation. Methods: The study involved 66 male T. guasayana specimens from 10 triatomine populations. Digital images of wing, head and pronotum were used to estimate linear and geometric morphometric variables. Variations in size and shape were analysed using one-way analysis of variance and canonical variate analysis (CVA), respectively. Mantel tests were applied to analyse the relationship between morphometric and geographic distances, and the association between size measurements was analysed using Pearson's correlation. We explored covariation between size and shape variables using partial least square analyses (PLS). The association of geographic and climatic variables with size measurements was tested using linear regression analyses. We performed PLS analyses for shape measurements. Results: Wing size differed significantly across triatomine populations. The CVA showed that wing shape of the brachypterous population is well discriminated from that of the other populations. The Mantel test showed a positive and significant association between wing shape and geographic distances. The heads of the brachypterous population were significantly larger than those of the other populations. Similar to wing shape, the head shape of the brachypterous population was well discriminated from those of the other populations. Pronotum width did not show significant differences across populations. Geographic and climatic factors were associated with size and shape of both the wing and head, but not with pronotum width. Conclusions: Most of the traits related to flight dispersal varied across populations. Wing shape and head shape were found to be better markers for differentiated morphological variation across populations. Head measurements also varied in accordance with this condition. Geographic and climatic variables were associated with most of the flight-related traits. [ABSTRACT FROM AUTHOR]

Background: Triatoma dimidiata is a vector of the protozoan parasite Trypanosoma cruzi, the etiologic agent of Chagas disease. Phenotypic plasticity allows an organism to adjust its phenotype in response to stimuli or environmental conditions. Understanding the effect of T. cruzi on the phenotypic plasticity of its vectors, known as triatomines, has attracted great interest because of the implications of the parasite–triatomine interactions in the eco-epidemiology and transmission of the etiologic agent of Chagas disease. We investigated if the infection of the vector with T. cruzi may be associated with a change in the antennal phenotype of sylvatic, domestic, and laboratory-reared populations of T. dimidiata. Methods: The abundance of each type of sensillum (bristles, basiconic, thick- and thin-walled trichoid) on the antennae of T.cruzi-infected and non-infected T.dimidiata reared in the laboratory or collected in sylvatic and domestic ecotopes were measured under light microscopy and compared using Kruskal–Wallis non-parametric tests and permutational multivariate analysis of variance. Results: We found significant differences between sensilla patterns of infected and non-infected insects within sylvatic and domestic populations. Conversely, we found no significant differences between sensilla patterns of infected and non-infected insects within the laboratory-reared population. Besides, for sylvatic and domestic populations, sexual dimorphism tended to be increased in infected insects. Conclusion: The differences observed in infected insects could be linked to higher efficiency in the perception of odor molecules related to the search for distant mates and hosts and the flight dispersal in search of new habitats. In addition, these insects could have a positive effect on population dynamics and the transmission of T.cruzi. [ABSTRACT FROM AUTHOR]

Background: Chagas disease is considered to be endemic in up to 40% of the territory of Colombia, and to date 27 triatomine species have been reported the country. The purpose of this study was to update the geographical distribution of triatomine species in Colombia and assess the species richness patterns and their altitudinal distribution. Methods: Occurrence data were compiled between 2007 and 2020, including from reports of entomological surveillance from the Instituto Nacional de Salud (INS), the Centro de Investigaciones en Microbiología y Parasitología Tropical (CIMPAT) at Universidad de Los Andes and a review of the literature. Geographic Information Systems (GIS) were used to describe general species richness patterns of the Triatominae subfamily. To establish the altitudinal distribution of the triatomine species, ranges were obtained from reports with unique elevation values. A generalized linear model was fitted, based on a Poisson distribution, to test the relation between triatomine species richness and Chagas disease cases (2012–2019). Results: An updated geographical and altitudinal distribution for triatomine species in Colombia was established, with 507 municipalities added to the previously known distributions. The greatest triatomine richness in Colombia was found to be concentrated in the northeastern region of the country, extending towards the center to the departments of Arauca, Casanare and Meta. Regarding the altitudinal distribution, the study revealed that the species Rhodnius prolixus and Triatoma dimidiata have the greatest altitudinal ranges. The data also suggest a positive relation between species richness and number of Chagas disease cases reported per department. Conclusions: Altitudinal ranges for 17 triatomine species found in Colombia are presented. Species richness and species composition patterns are also described, and areas with a higher risk of transmission based on the relation found with Chagas disease cases are highlighted. This updated distribution reveals that Panstrongylus geniculatus is the triatomine with the largest presence by municipalities in Colombia, being reported in 284 municipalities, followed by Rhodnius prolixus in 277 municipalities. [ABSTRACT FROM AUTHOR]

Chagas disease is a neglected tropical disease in Latin America and an imported emerging disease worldwide. Chronic Chagas disease cardiomyopathy (CCC) is the most prominent clinical form and can lead to heart failure, thromboembolism, and sudden death. While previous reports have supported a role for CD4+ T lymphocytes in the pathogenesis of CCC a comprehensive analysis of these cells during different clinical forms is lacking. Here, we used high-dimensional flow cytometry to assess the diversity of circulating CD4+ T cells in patients with distinct clinical forms. We found increased frequencies of CD4+CD69+ T cells in patients compared to controls. CD39+ regulatory T cells, represented by mesocluster 6 were reduced in mild CCC patients compared to controls. Cytotoxic CD4+ T cells co-expressing granzyme B and perforin were expanded in patients with Chagas disease and were higher in patients with mild CCC compared to controls. Furthermore, patients with mild CCC displayed higher frequencies of multifunctional effector memory CD4+ T cells. Our results demonstrate an expansion in activated CD4+ T cells and a decrease in a functional subset of regulatory T cells associated with the onset of Chagas cardiomyopathy, suggesting their role in the establishment of cardiac lesions and as potential biomarkers for disease aggravation. [ABSTRACT FROM AUTHOR]

Background: Although Chagas cardiomyopathy is related to thromboembolic stroke, data on risk factors for cerebrovascular events in Chagas disease is limited. Thus, we assessed the relationship between left ventricular (LV) impairment and cerebrovascular events and sources of thromboembolism in patients with Chagas cardiomyopathy. Methods: This retrospective cohort included patients with chronic Chagas cardiomyopathy who underwent cardiovascular magnetic resonance (CMR). CMR was performed with a 1.5 T scanner to provide LV volumes, mass, ejection fraction (LVEF), and myocardial fibrosis. The primary outcome was a composite of incident ischemic cerebrovascular events (stroke or transient ischemic attack—TIA) and potential thromboembolic sources (atrial fibrillation (AF), atrial flutter, or intracavitary thrombus) during the follow-up. Results: A total of 113 patients were included. Median age was 56 years (IQR: 45–67), and 58 (51%) were women. The median LVEF was 53% (IQR: 41–62). LV aneurysms and LV fibrosis were present in 38 (34%) and 76 (67%) individuals, respectively. The median follow-up time was 6.9 years, with 29 events: 11 cerebrovascular events, 16 had AF or atrial flutter, and two had LV apical thrombosis. In the multivariable model, only lower LVEF remained significantly associated with the outcomes (HR: 0.96, 95% CI: 0.93–0.99). Patients with reduced LVEF lower than 40% had a much higher risk of cerebrovascular events and thromboembolic sources (HR: 3.16 95% CI: 1.38–7.25) than those with normal LVEF. The combined incidence rate of the combined events in chronic Chagas cardiomyopathy patients with reduced LVEF was 13.9 new cases per 100 persons-year. Conclusions: LV systolic dysfunction is an independent predictor of adverse cerebrovascular events and potential sources of thromboembolism in patients with chronic Chagas cardiomyopathy. [ABSTRACT FROM AUTHOR]

Background: Since the late twentieth century, Chagas disease gained global attention to suppress the vector burden as a main control strategy in endemic countries. In Central America, multi-national initiative successfully achieved significant reduction in the estimated disease prevalence as well as elimination of the region's principal vector species at the time in 2012. While the last decade has witnessed significant changes in ecosystem—such as urbanization and replacement of the main vector species—that can possibly affect the vector's habitation and residual transmission, the up-to-date vector burden in the region has not been evaluated thoroughly due to the cessation of active vector surveillance. The aim of this study was to update the risk of vector-borne Trypanosoma cruzi infection in El Salvador, the top Chagas disease-endemic country in Central America. Methods: A nationwide vector survey was conducted in the domestic environment of El Salvador from September 2018 to November 2020. The selection of the houses for inspection was based on expert purposeful sampling. Infection for T. cruzi was examined by microscopic observation of the insects' feces, followed by a species confirmation using PCR. The data were analyzed using R software version 4.1.3. Proportion estimates with 95% confidence intervals were inferred using the Jeffrey's method provided under the epiR package. Results: A total of 1529 Triatoma dimidiata was captured from 107 houses (infestation rate, 34.4%; 107/311) in all the fourteen departments of the country visited within the period; prevalence of T. cruzi infection was as high as 10% (153/1529). In the country, domestic T. dimidiata infestation was distributed ubiquitously, while T. cruzi infection rates varied across the departments. Five out of fourteen departments showed higher infection rates than the average, suggesting sporadic high-risk areas in the country. Conclusions: Our comprehensive study revealed substantial T. cruzi infection of T. dimidiata across the country, indicating potential active transmission of the disease. Therefore, strengthened surveillance for both vector and human infection is required to truly eliminate the risk of T. cruzi transmission in Central America. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Dysautonomia plays an ancillary role in the pathogenesis of Chronic Chagas Cardiomyopathy (CCC), but is the key factor causing digestive organic involvement. We investigated the ability of heart rate variability (HRV) for death risk stratification in CCC and compared alterations of HRV in patients with isolated CCC and in those with the mixed form (CCC + digestive involvement). Thirty-one patients with CCC were classified into three risk groups (low, intermediate and high) according to their Rassi score. A single-lead ECG was recorded for a period of 10–20 min, RR series were generated and 31 HRV indices were calculated. The HRV was compared among the three risk groups and regarding the associated digestive involvement. Four machine learning models were created to predict the risk class of patients. Results: Phase entropy is decreased and the percentage of inflection points is increased in patients from the high-, compared to the low-risk group. Fourteen patients had the mixed form, showing decreased triangular interpolation of the RR histogram and absolute power at the low-frequency band. The best predictive risk model was obtained by the support vector machine algorithm (overall F1-score of 0.61). Conclusions: The mixed form of Chagas' disease showed a decrease in the slow HRV components. The worst prognosis in CCC is associated with increased heart rate fragmentation. The combination of HRV indices enhanced the accuracy of risk stratification. In patients with the mixed form of Chagas disease, a higher degree of sympathetic autonomic denervation may be associated with parasympathetic impairment. [ABSTRACT FROM AUTHOR]

Background: Rhodnius robustus and Rhodnius pictipes are vectors of Trypanosoma cruzi, the etiologic agent of Chagas disease (CD), that are found in the Brazilian Amazon region. Susceptibility to infection and vector competence depend on the parasite-vector relationship. Our objective was to evaluate the interaction between T. cruzi and these two triatomine vectors in pure and mixed experimental infections of T. cruzi strains from the same or different geographic regions. Methods: Fifth-instar nymphs of R. robustus and R. pictipes were fed on mice infected with four T. cruzi strains, namely genotypes TcIAM, TcIMG, TcIIPR, and TcIVAM, respectively, from the Brazilian states of Amazonas, Minas Gerais and Paraná. Over a period of 120 days, excreta were examined every 20 days to assess vector competence, and intestinal contents (IC) were examined every 30 days to determine susceptibility to infection. Results: The highest positive rate in the fresh examination (%+FE, 30.0%), the highest number of parasitic forms (PF, n = 1969) and the highest metacyclogenesis rate (%MC, 53.8%) in the excreta were recorded for R. robustus/TcIVAM. Examination of the IC of R. pictipes revealed a higher number of PF in infections with TcIAM (22,680 PF) and TcIIPR (19,845 PF) alone or in association (17,145 PF), as well as a %+FE of 75.0% with TcII, in comparison with the other genotypes. The highest %MC (100%) was recorded for the mixed infections of TcIAM with TcIIPR or TcIVAM in the IC of R. pictipes. Conclusions: Overall, both species were found to be susceptible to the T. cruzi strains studied. Rhodnius robustus showed vector competence for genotypes TcIVAM and TcIAM+TcIVAM and R. pictipes for TcIAM+TcIVAM and TcIAM+TcIIPR; there was elimination of infective forms as early as at 20 days. Our results suggest that both the genetics of the parasite and its geographic origin influence the susceptibility to infection and vector competence, alone or in association. [ABSTRACT FROM AUTHOR]

Background: Among the 18 genera of the Triatominae subfamily, three stand out for their diversity and epidemiological importance: Triatoma, Panstrongylus, and Rhodnius. Rhodnius includes 21 species that can transmit Trypanosoma cruzi (the etiological agent of Chagas disease, also known as American trypanosomiasis) and Trypanosoma rangeli. The Rhodnius prolixus complex comprises seven species, including Rhodnius marabaensis, Rhodnius prolixus, and Rhodnius robustus, which occur in the northern region of Brazil. Since both adults and immatures can carry T. cruzi, in this study the five nymphal instars of the three species mentioned were dorsally characterized. Methods: Using microscopy, morphometrics, and geometric morphometrics, the present work measures and describes the morphological characters of the five nymphal instars of R. marabaensis, R. prolixus, and R. robustus. Results: The study enabled the characterization of all five nymphal instars, as well as the distinction between the three species in each of their instars. Conclusions: The morphological, morphometrics of the head, thorax, and abdomen and geometric morphometrics studies of the head enabled the specific distinction of these three species in all five instars. [ABSTRACT FROM AUTHOR]

Background: Triatomines in Latin America are natural Chagas disease (ChD) vectors. Triatomine domiciliation is one of the main factors increasing the occurrence risk of this disease in humans. There are 66 triatomine species in Brazil, with three genera of significant epidemiological importance—Panstrongylus, Rhodnius, and Triatoma. Among the Triatoma species, Triatoma williami, a wild species, has been reported in Goiás, Mato Grosso, and Mato Grosso do Sul. In the Barra do Garças, Mato Grosso, the invasion by triatomines has been reported, with T. williami being the most common species. This study aimed to survey triatomine fauna and determine the Trypanosoma cruzi natural infection rates in triatomines in the urban area of Barra do Garças, Mato Grosso, Brazil. Methods: Triatomine specimens were sampled by passive surveillance or active search by agents combating endemic diseases from 2019 to 2020. A parasitological feces diagnosis was performed to detect the presence of T. cruzi after the specimens were identified. Concerning T. cruzi identification, molecular diagnosis and genetic sequencing were performed to determine the strain, also called discrete typing units (DTUs). Results: The 211 triatomines were collected, distributed in specimens of T. williami (84.4%), P. geniculatus (3.3%), P. diasi (1.4%), and R. neglectus (10.9%). Two colonies of T. williami were found through morphological analyses. These insects were sampled inside domiciles in an urban area neighboring Jardim Pitaluga (15° 51′57.7″ N, 052° 16′ 04.5 E). The records were sampled in September 2019 and January 2021. The rate of natural infection by T. cruzi was 39.4%. Two T. williami specimens from the sampled colonies were positive for the T. cruzi strain DTU IV. Conclusions: This is the first time that T. williami has been confirmed in an urban area of Barra do Garças, Mato Grosso, Brazil. Further studies are needed for a clearer understanding of the ecology of this species for prevention and control mechanisms since its sampled specimens had a high rate of natural infection by T. cruzi. [ABSTRACT FROM AUTHOR]

Background: The distribution of parasite load across hosts may modify the transmission dynamics of infectious diseases. Chagas disease is caused by a multi-host protozoan, Trypanosoma cruzi, but the association between host parasitemia and infectiousness to the vector has not been studied in sylvatic mammalian hosts. We quantified T. cruzi parasite load in sylvatic mammals, modeled the association of the parasite load with infectiousness to the vector and compared these results with previous ones for local domestic hosts. Methods: The bloodstream parasite load in each of 28 naturally infected sylvatic mammals from six species captured in northern Argentina was assessed by quantitative PCR, and its association with infectiousness to the triatomine Triatoma infestans was evaluated, as determined by natural or artificial xenodiagnosis. These results were compared with our previous results for 88 humans, 70 dogs and 13 cats, and the degree of parasite over-dispersion was quantified and non-linear models fitted to data on host infectiousness and bloodstream parasite load. Results: The parasite loads of Didelphis albiventris (white-eared opossum) and Dasypus novemcinctus (nine-banded armadillo) were directly and significantly associated with infectiousness of the host and were up to 190-fold higher than those in domestic hosts. Parasite load was aggregated across host species, as measured by the negative binomial parameter, k, and found to be substantially higher in white-eared opossums, cats, dogs and nine-banded armadillos (range: k = 0.3–0.5) than in humans (k = 5.1). The distribution of bloodstream parasite load closely followed the "80–20 rule" in every host species examined. However, the 20% of human hosts, domestic mammals or sylvatic mammals exhibiting the highest parasite load accounted for 49, 25 and 33% of the infected triatomines, respectively. Conclusions: Our results support the use of bloodstream parasite load as a proxy of reservoir host competence and individual transmissibility. The over-dispersed distribution of T. cruzi bloodstream load implies the existence of a fraction of highly infectious hosts that could be targeted to improve vector-borne transmission control efforts toward interruption transmission. Combined strategies that decrease the parasitemia and/or host–vector contact with these hosts would disproportionally contribute to T. cruzi transmission control. [ABSTRACT FROM AUTHOR]

Age-stratified serosurvey data are often used to understand spatiotemporal trends in disease incidence and exposure through estimating the Force-of-Infection (FoI). Typically, median or mean FoI estimates are used as the response variable in predictive models, often overlooking the uncertainty in estimated FoI values when fitting models and evaluating their predictive ability. To assess how this uncertainty impact predictions, we compared three approaches with three levels of uncertainty integration. We propose a performance indicator to assess how predictions reflect initial uncertainty.In Colombia, 76 serosurveys (1980-2014) conducted at municipality level provided age-stratified Chagas disease prevalence data. The yearly FoI was estimated at the serosurvey level using a time-varying catalytic model. Environmental, demographic and entomological predictors were used to fit and predict the FoI at municipality level from 1980 to 2010 across Colombia.A stratified bootstrap method was used to fit the models without temporal autocorrelation at the serosurvey level. The predictive ability of each model was evaluated to select the best-fit models within urban, rural and (Amerindian) indigenous settings. Model averaging, with the 10 best-fit models identified, was used to generate predictions.Our analysis shows a risk of overconfidence in model predictions when median estimates of FoI alone are used to fit and evaluate models, failing to account for uncertainty in FoI estimates. Our proposed methodology fully propagates uncertainty in the estimated FoI onto the generated predictions, providing realistic assessments of both central tendency and current uncertainty surrounding exposure to Chagas disease. [ABSTRACT FROM AUTHOR]

Background: Indoor residual spraying (IRS) of insecticides is a key method to reduce vector transmission of Trypanosoma cruzi, causing Chagas disease in a large part of South America. However, the successes of IRS in the Gran Chaco region straddling Bolivia, Argentina, and Paraguay, have not equalled those in other Southern Cone countries. Aims: This study evaluated routine IRS practices and insecticide quality control in a typical endemic community in the Bolivian Chaco. Methods: Alpha-cypermethrin active ingredient (a.i.) captured onto filter papers fitted to sprayed wall surfaces, and in prepared spray tank solutions, were measured using an adapted Insecticide Quantification Kit (IQK™) validated against HPLC quantification methods. The data were analysed by mixed-effects negative binomial regression models to examine the delivered insecticide a.i. concentrations on filter papers in relation to the sprayed wall heights, spray coverage rates (surface area / spray time [m2/min]), and observed/expected spray rate ratios. Variations between health workers and householders' compliance to empty houses for IRS delivery were also evaluated. Sedimentation rates of alpha-cypermethrin a.i. post-mixing of prepared spray tanks were quantified in the laboratory. Results: Substantial variations were observed in the alpha-cypermethrin a.i. concentrations delivered; only 10.4% (50/480) of filter papers and 8.8% (5/57) of houses received the target concentration of 50 mg ± 20% a.i./m2. The delivered concentrations were not related to those in the matched spray tank solutions. The sedimentation of alpha-cypermethrin a.i. in the surface solution of prepared spray tanks was rapid post-mixing, resulting in a linear 3.3% loss of a.i. content per minute and 49% loss after 15 min. Only 7.5% (6/80) of houses were sprayed at the WHO recommended rate of 19 m2/min (± 10%), whereas 77.5% (62/80) were sprayed at a lower than expected rate. The median a.i. concentration delivered to houses was not significantly associated with the observed spray coverage rate. Householder compliance did not significantly influence either the spray coverage rates or the median alpha-cypermethrin a.i. concentrations delivered to houses. Conclusions: Suboptimal delivery of IRS is partially attributable to the insecticide physical characteristics and the need for revision of insecticide delivery methods, which includes training of IRS teams and community education to encourage compliance. The IQK™ is a necessary field-friendly tool to improve IRS quality and to facilitate health worker training and decision-making by Chagas disease vector control managers. [ABSTRACT FROM AUTHOR]

Background: Triatomine bugs, the vectors of Chagas disease, associate with vertebrate hosts in highly diverse ecotopes. It has been proposed that occupation of new microhabitats may trigger selection for distinct phenotypic variants in these blood-sucking bugs. Although understanding phenotypic variation is key to the study of adaptive evolution and central to phenotype-based taxonomy, the drivers of phenotypic change and diversity in triatomines remain poorly understood. Methods/results: We combined a detailed phenotypic appraisal (including morphology and morphometrics) with mitochondrial cytb and nuclear ITS2 DNA sequence analyses to study Rhodnius ecuadoriensis populations from across the species' range. We found three major, naked-eye phenotypic variants. Southern-Andean bugs primarily from vertebrate-nest microhabitats (Ecuador/Peru) are typical, light-colored, small bugs with short heads/wings. Northern-Andean bugs from wet-forest palms (Ecuador) are dark, large bugs with long heads/wings. Finally, northern-lowland bugs primarily from dry-forest palms (Ecuador) are light-colored and medium-sized. Wing and (size-free) head shapes are similar across Ecuadorian populations, regardless of habitat or phenotype, but distinct in Peruvian bugs. Bayesian phylogenetic and multispecies-coalescent DNA sequence analyses strongly suggest that Ecuadorian and Peruvian populations are two independently evolving lineages, with little within-lineage phylogeographic structuring or differentiation. Conclusions: We report sharp naked-eye phenotypic divergence of genetically similar Ecuadorian R. ecuadoriensis (nest-dwelling southern-Andean vs palm-dwelling northern bugs; and palm-dwelling Andean vs lowland), and sharp naked-eye phenotypic similarity of typical, yet genetically distinct, southern-Andean bugs primarily from vertebrate-nest (but not palm) microhabitats. This remarkable phenotypic diversity within a single nominal species likely stems from microhabitat adaptations possibly involving predator-driven selection (yielding substrate-matching camouflage coloration) and a shift from palm-crown to vertebrate-nest microhabitats (yielding smaller bodies and shorter and stouter heads). These findings shed new light on the origins of phenotypic diversity in triatomines, warn against excess reliance on phenotype-based triatomine-bug taxonomy, and confirm the Triatominae as an informative model system for the study of phenotypic change under ecological pressure. [ABSTRACT FROM AUTHOR]

Background: Vectorial transmission is the principal path of infection by Trypanosoma cruzi, the parasite that causes Chagas disease. In Argentina, Triatoma infestans is the principal vector; therefore, vector control is the main strategy for the prevention of this illness. The Provincial Program of Chagas La Rioja (PPCHLR) carries out entomological evaluation of domiciliary units (DUs) and spraying of those where T. infestans is found. The lack of government funds has led to low visitation frequency by the PPCHLR, especially in areas with a low infestation rate, which are not prioritized. Therefore, seeking possible alternatives to complement control activities is necessary. Involving householders in entomological evaluation could be a control alternative. The major objective was to determine the cost of entomological evaluation with and without community participation. Methods: For entomological evaluation without community participation, PPCHLR data collected in February 2017 over 359 DUs of the Castro Barros Department (CBD) were used. For entomological evaluation with community participation, 434 DUs of the same department were selected in November 2017. Each householder was trained in collecting insects, which were kept in labeled plastic bags, recovered after 2 weeks, and analyzed in the laboratory for the presence of T. cruzi. Using householders' collection data, a spatial scan statistic was used to detect clusters of different T. infestans infestations. Entomological evaluation costs with and without community participation related to the numbers of DUs visited, DUs evaluated, and DUs sprayed were calculated and compared between methodologies. In addition, the number of DUs evaluated of the DUs visited was compared. Results: According to the results, the triatomines did not show evidence of T. cruzi infection. Spatial analysis detected heterogeneity of T. infestans infestation in the area. Costs related to the DUs visited, evaluated, and sprayed were lower with community participation (p < 0.05). In addition, more DUs were evaluated in relation to those visited and a greater surface area was covered with community participation. Conclusion: Participation of the community in the infestation survey is an efficient complement to vertical control, allowing the spraying to be focused on infested houses and thus reducing the PPCHLR's costs and intervention times. [ABSTRACT FROM AUTHOR]

Background: Chagas disease remains a significant public health problem in Latin America. There are only two chemotherapy drugs, nifurtimox and benznidazole, and both may have severe side effects. After complete chemotherapy of acute cases, seropositive diagnosis may revert to negative. However, there are no definitive parasitological or serological biomarkers of cure. Methods: Following a pilot study with seven Bolivian migrants to Spain, we tested 71 serum samples from chronic patients (mean age 12.6 years) inhabiting the Argentine Chaco region. Benznidazole chemotherapy (5–8 mg/kg day, twice daily for 60 days) was administered during 2011–2016. Subsequently, pre-and post-chemotherapy serum samples were analysed in pairs by IgG1 and IgG ELISA using two different antigens and Chagas Sero K-SeT rapid diagnostic tests (RDT). Molecular diagnosis by kDNA-PCR was applied to post-treatment samples. Results: Pilot data demonstrated IgG1 antibody decline in three of seven patients from Bolivia 1 year post-treatment. All Argentine patients in 2017 (averaging 5 years post-treatment), except one, were positive by conventional serology. All were kDNA-PCR-negative. Most (91.5%) pre-treatment samples were positive by the Chagas Sero K-SeT RDT, confirming the predominance of TcII/V/VI. IgG1 and IgG of Argentine patients showed significant decline in antibody titres post-chemotherapy, with either lysate (IgG, P = 0.0001, IgG1, P = 0.0001) or TcII/V/VI peptide antigen (IgG, P = 0.0001, IgG1, P = 0.0001). IgG1 decline was more discriminative than IgG. Antibody decline after treatment was also detected by the RDT. Incomplete treatment was associated with high IgG1 post-treatment titres against lysate (P = 0.013), as were IgG post-treatment titres to TcII/V/VI peptide (P = 0.0001). High pre-treatment IgG1 with lysate was associated with Qom ethnicity (P = 0.045). No associations were found between gender, age, body mass index and pre- or post-treatment antibody titres. Conclusions: We show that following chemotherapy of early chronic Chagas disease, significant decline in IgG1 antibody suggests cure, whereas sustained or increased IgG1 is a potential indicator of treatment failure. Due to restricted sensitivity, IgG1 should not be used as a diagnostic marker but has promise, with further development, as a biomarker of cure. We show that following chemotherapy of early chronic Chagas disease, a significant decline in IgG1 antibody suggests cure, whereas sustained or increased IgG1 is a potential indicator of treatment failure. Due to restricted sensitivity, IgG1 should not be used as a diagnostic marker but has promise, with further development, as a biomarker of cure. [ABSTRACT FROM AUTHOR]

Background: Colombia's National Army is one of the largest military institutions in the country based on the number of serving members and its presence throughout the country. There have been reports of cases of acute or chronic cases of Chagas disease among active military personnel. These may be the result of military-associated activities performed in jungles and other endemic areas or the consequence of exposure to Trypanosoma cruzi inside military establishments/facilities located in endemic areas. The aim of the present study was to describe the circulation of T. cruzi inside facilities housing four training and re-training battalions [Battalions of Instruction, Training en Re-training (BITERs)] located in municipalities with historical reports of triatomine bugs and Chagas disease cases. An entomological and faunal survey of domestic and sylvatic environments was conducted inside each of these military facilities. Methods: Infection in working and stray dogs present in each BITER location was determined using serological and molecular tools, and T. cruzi in mammal and triatomine bug samples was determined by PCR assay. The PCR products of the vertebrate 12S rRNA gene were also obtained and subjected to Sanger sequencing to identify blood-feeding sources. Finally, we performed a geospatial analysis to evaluate the coexistence of infected triatomines and mammals with the military personal inside of each BITER installation. Results: In total, 86 specimens were collected: 82 Rhodnius pallescens, two Rhodnius prolixus, one Triatoma dimidiata and one Triatoma maculata. The overall T. cruzi infection rate for R. pallescens and R. prolixus was 56.1 and 100% respectively, while T. dimidiata and T. maculata were not infected. Eight feeding sources were found for the infected triatomines, with opossum and humans being the most frequent sources of feeding (85.7%). Infection was most common in the common opossum Didelphis marsupialis, with infection levels of 77.7%. Sylvatic TcI was the most frequent genotype, found in 80% of triatomines and 75% of D. marsupialis. Of the samples collected from dogs (n = 52), five (9.6%; 95% confidence interval: 3.20–21.03) were seropositive based on two independent tests. Four of these dogs were creole and one was a working dog. The spatial analysis revealed a sympatry between infected vectors and mammals with the military population. Conclusions: We have shown a potential risk of spillover of sylvatic T. cruzi transmission to humans by oral and vectorial transmission in two BITER installations in Colombia. The results indicate that installations where 100,000 active military personnel carry out training activities should be prioritized for epidemiological surveillance of Chagas disease. [ABSTRACT FROM AUTHOR]

Background: Triatomine bugs transmit Chagas disease across Latin America, where vector control-surveillance is increasingly decentralized. Locally run systems often deal with highly diverse native-vector faunas—plus, in some areas, domestic populations of non-native species. Flexible entomological-risk indicators that cover native and non-native vectors and can support local decision-making are therefore needed. Methods: We present a local-scale entomological-risk score ("TriatoScore") that leverages and builds upon information on the ecology-behavior and distribution-biogeography of individual triatomine bug species. We illustrate our approach by calculating TriatoScores for the 417 municipalities of Bahia state, Brazil. For this, we (i) listed all triatomine bug species recorded statewide; (ii) derived a "species relevance score" reflecting whether each species is native/non-native and, if native, whether/how often it invades/colonizes dwellings; (iii) mapped each species' presence by municipality; (iv) for native vectors, weighted presence by the proportion of municipal territory within ecoregions occupied by each species; (v) multiplied "species relevance score" × "weighted presence" to get species-specific "weighted scores"; and (vi) summed "weighted scores" across species to get municipal TriatoScores. Using standardized TriatoScores, we then grouped municipalities into high/moderate/low entomological-risk strata. Results: TriatoScores were higher in municipalities dominated by dry-to-semiarid ecoregions than in those dominated by savanna-grassland or, especially, moist-forest ecoregions. Bahia's native triatomines can maintain high to moderate risk of vector-borne Chagas disease in 318 (76.3%) municipalities. Historical elimination of Triatoma infestans from 125 municipalities reduced TriatoScores by ~ 27% (range, 20–44%); eight municipalities reported T. infestans since Bahia was certified free of Trypanosoma cruzi transmission by this non-native species. Entomological-risk strata based on TriatoScores agreed well with Bahia's official disease-risk strata, but TriatoScores suggest that the official classification likely underestimates risk in 42 municipalities. Of 152 municipalities failing to report triatomines in 2006–2019, two and 71 had TriatoScores corresponding to, respectively, high and moderate entomological risk. Conclusions: TriatoScore can help control-surveillance managers to flexibly assess and stratify the entomological risk of Chagas disease at operationally relevant scales. Integrating eco-epidemiological, demographic, socioeconomic, or operational data (on, e.g., local-scale dwelling-infestation or vector-infection frequencies, land-use change and urbanization, housing conditions, poverty, or the functioning of control-surveillance systems) is also straightforward. TriatoScore may thus become a useful addition to the triatomine bug control-surveillance toolbox. [ABSTRACT FROM AUTHOR]

Background: Chagas disease is a parasitic disease endemic to Latin America, but it has become a disease of global concern due to migration flows. Asymptomatic carriers may host the parasite for years, without knowing they are infected. The aim of this study is to assess prevalence of Chagas disease and evaluate the participants' level of knowledge between Latin American migrants attending a community-based screening campaign. Methods: Three community-based campaigns were performed in Alicante (Spain) in 2016, 2017 and 2018, including educational chats and blood tests for Trypanosoma cruzi serology. Participants completed a questionnaire assessing knowledge about the mechanisms of transmission, disease presentation, diagnosis, and treatment. People seropositive for T. cruzi underwent diagnostic confirmation by two different tests. Results were analyzed by multivariable logistic regression and expressed as adjusted odds ratios (aORs), adjusting for age, sex, and time in Spain. Results: A total of 596 participants were included in the study; 17% were aged under 18 years. Prevalence in adults was 11% [54/496; 95% confidence interval (CI): 8.3–14.5%] versus 0% among children. All but one case were in Bolivians. Diagnosis was independently associated with having been born in Bolivia (aOR: 102, 95% CI: 13–781) and a primary school-level education (aOR: 2.40, 95% CI: 1.14–5.06). Of 54 people diagnosed with Chagas disease (most of whom were asymptomatic), 42 (77.7%) returned to the clinic at least once, and 24 (44.4%) received treatment. Multivariable analysis showed that coming from Argentina (aOR: 13, 95% CI: 1.61–1188) or Bolivia (aOR: 1.90, 95% CI: 1.19–3.39) and having received information about Chagas disease in Spain (aOR: 4.63, 95% CI: 2.54–8.97) were associated with a good level of knowledge on the disease. Having primary level studies (aOR: 0.59, 95% CI: 0.34–0.98) and coming from Ecuador (aOR: 4.63, 95% CI: 2.52–847) were independently associated with a lower level of knowledge. Conclusions: Community-based interventions are a good strategy for diagnosing neglected diseases such as Chagas disease in non-endemic countries and for identifying and treating infected, asymptomatic individuals. [ABSTRACT FROM AUTHOR]

Background: Triatomines are responsible for the vector transmission of the protozoan parasite Trypanosoma cruzi, which causes Chagas disease. Triatoma brasiliensis is the main vector of the parasite in Brazil, and dogs are an important reservoir of the parasite. The aim of this study was to evaluate the insecticidal effect of fluralaner (Bravecto®) on T. brasiliensis after a blood meal in treated dogs. Methods: Healthy mongrel dogs (n = 8) were recruited from the Zoonoses Control Center (ZCC) in the city of Natal, Rio Grande do Norte, Brazil, and randomized into two groups, a fluralaner (Bravecto®)-treated group (n = 4) and a control group (n = 4). Colony-reared third-, fourth- and fifth-instar nymphs of T. brasiliensis nymphs (n = 10) were allowed to feed on dogs from both groups for 30–40 min, once monthly, for up to 12 months. Bug mortality was observed up to 5 days after each blood meal. Results: Mortality in triatomines which had a blood meal on fluralaner (Bravecto®)-treated dogs was 100% for up to 7 months after treatment, with mortality decreasing to 66.4% after 8 months, 57% after 9 months, 35% after 10 months, 10% after 11 months and 0% after 12 months. The mortality of triatomines that fed on non-treated control dogs was always ≤ 2.5%. Conclusions: Our results suggest that fluralaner (Bravecto®) treatment of dogs induces long-term mortality of T. brasiliensis after the blood meal. This is a potential approach to be used to control vector transmission of T. cruzi, the etiological agent of Chagas disease, especially in endemic areas. [ABSTRACT FROM AUTHOR]

Background: Chagas disease is considered important and presents intense inflammatory and fibrotic processes induced by the perpetuation of the parasite in the affected tissues and organs. Therefore, it is necessary to inquire about the host defense and attack mechanisms to have a more detailed knowledge about Chagas disease. MicroRNAs are found in blood, tissues and extracellular vesicles. These small regulators of gene expression are involved in physiological and pathological processes in both mammals and parasites. Several microRNAs have deregulated expression in chagasic heart disease, although little is known about their extracellular expression. Our main objective was to evaluate the involvement of miR-21, miR-146a and miR-155 in several samples from mice infected with the TcI Ninoa strain from the acute and indeterminate phases. We also explored a potential functional association of the selected microRNAs using STRING software. This software identified 23 pathways associated with Trypanosoma cruzi infection. In addition, eleven genes were identified through bioinformatics analysis, and we found that SMAD family member 5 was downregulated in both phases. This gene serves as a mediator in the TGF-β signaling pathway. Thus, forty female mice of the CD1 strain were distributed into 4 groups and the expression levels of miR-21, miR-146a and miR-155 were measured in samples of heart tissue, total plasma and plasma extracellular vesicles by quantitative real-time polymerase chain reaction. Results: Overexpression of miR-21, miR-146a and miR-155 was observed in heart and plasma in both phases. Moreover, in extracellular vesicles miR-21 and miR-146a were also overexpressed in the acute phase, whereas in the indeterminate chronic phase we found only miR-146a up-regulated. Conclusions: The expression of inflammatory microRNAs miR-21, miR-146a and miR-155 were up-regulated in each of the samples from acutely and chronically infected mice. The relevant finding was that miR-146a was up-regulated in each sample in both phases; therefore, this miRNA could be a possible candidate biomarker in Chagas disease. [ABSTRACT FROM AUTHOR]

Background: Parasite persistence, exacerbated and sustained immune response, and continuous oxidative stress have been described to contribute to the development of the cardiac manifestations in Chronic Chagas Disease. Nevertheless, there are no efficient therapies to resolve the Trypanosoma cruzi infection and prevent the disease progression. Interestingly, trypanocide, antioxidant, and immunodulatory properties have been reported separately for some major terpenes, as citral (neral plus geranial), limonene, and caryophyllene oxide, presents in essential oils (EO) extracted from two chemotypes (Citral and Carvone) of Lippia alba. The aim of this study was to obtain L. alba essential oil fractions enriched with the aforementioned bioactive terpenes and to evaluate the impact of these therapies on trypanocide, oxidative stress, mitochondrial bioenergetics, genotoxicity, and inflammatory markers on T. cruzi-infected macrophages. Methods: T. cruzi-infected J774A.1 macrophage were treated with limonene-enriched (ACT1) and citral/caryophyllene oxide-enriched (ACT2) essential oils fractions derived from Carvone and Citral-L. alba chemotypes, respectively. Results: ACT1 (IC50 = 45 ± 1.7 μg/mL) and ACT2 (IC50 = 80 ± 1.9 μg/mL) exhibit similar trypanocidal effects to Benznidazole (BZN) (IC50 = 48 ± 2.5 μg/mL), against amastigotes. Synergistic antiparasitic activity was observed when ACT1 was combined with BZN (∑FIC = 0.52 ± 0.13 μg/mL) or ACT2 (∑FIC = 0.46 ± 1.7 μg/mL). ACT1 also decreased the oxidative stress, mitochondrial metabolism, and genotoxicity of the therapies. The ACT1 + ACT2 and ACT1 + BZN experimental treatments reduced the pro-inflammatory cytokines (IFN-γ, IL-2, and TNF-α) and increased the anti-inflammatory cytokines (IL-4 and IL-10). Conclusion: Due to its highly trypanocidal and immunomodulatory properties, ACT1 (whether alone or in combination with BZN or ACT2) represents a promising L. alba essential oil fraction for further studies in drug development towards the Chagas disease control. [ABSTRACT FROM AUTHOR]

Background: Chagas disease is a neglected zoonosis caused by the parasite Trypanosoma cruzi. It affects over six million people, mostly in Latin America. Drugs available to treat T. cruzi infection have associated toxicity and questionable efficacy at the chronic stage. Hence, the discovery of more effective and safer drugs is an unmet medical need. For this, natural products represent a pool of unique chemical diversity that can serve as excellent templates for the synthesis of active molecules. Methods: A collection of 79 extracts of Amaryllidaceae plants were screened against T. cruzi. Active extracts against the parasite were progressed through two cell toxicity assays based on Vero and HepG2 cells to determine their selectivity profile and discard those toxic to host cells. Anti-T. cruzi-specific extracts were further qualified by an anti-amastigote stage assay. Results: Two extracts, respectively from Crinum erubescens and Rhodophiala andicola, were identified as highly active and specific against T. cruzi and its mammalian replicative form. Conclusions: The results retrieved in this study encourage further exploration of the chemical content of these extracts in search of new anti-T. cruzi drug development starting points. [ABSTRACT FROM AUTHOR]

Background: Panstrongylus megistus is the most important vector of Chagas disease in Brazil. Studies show that the principal factor hindering the control of triatomines is reinfestation of houses previously treated with insecticides. Studies at the microgeographic level are therefore necessary to better understand these events. However, an efficient molecular marker is not yet available for carrying out such analyses in this species. The aim of the present study was to identify and characterize microsatellite loci for future population genetic studies of P. megistus. Methods: This study work consisted of five stages: (i) sequencing of genomic DNA; (ii) assembly and selection of contigs containing microsatellites; (iii) validation of amplification and evaluation of polymorphic loci; (iv) standardization of the polymorphic loci; and (v) verification of cross-amplification with other triatomine species. Results: Sequencing of males and females generated 7,908,463 contigs with a total length of 2,043,422,613 bp. A total of 2,043,690 regions with microsatellites in 1,441,091 contigs were obtained, with mononucleotide repeats being the most abundant class. From a panel of 96 loci it was possible to visualize polymorphisms in 64.55% of the loci. Of the 20 loci genotyped, the number of alleles varied from two to nine with an average of 4.9. Cross-amplification with other species of triatomines was observed in 13 of the loci. Conclusions: Due to the high number of alleles encountered, polymorphism and the capacity to amplify from geographically distant populations, the microsatellites described here show promise for utilization in population genetic studies of P. megistus. [ABSTRACT FROM AUTHOR]

Background: In the Brazilian Amazon, a new epidemiological profile of Chagas disease transmission, the oral route, has been detected and cited as being responsible for the increase in acute cases in Brazil. The clinical evaluation of acute Chagas disease (ACD) has been a challenge since it can progress to a chronic phase with cardiac alterations, and the follow-up by modern diagnostic methods is very difficult due to the socio-geographical characteristics of the Brazilian Amazon. Thus, alternatives should be sought to alleviate this problem. We conducted a study to evaluate subjects with ACD using the 12-lead ECG QRS score (Selvester score) as an estimative of myocardial injury progression before and after ACD treatment.Methods: The study included indigenous subjects from the Amazon region with ACD in clinical follow-up at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD) Chagas Disease outpatient clinic in the state of Amazonas, Brazil. The control group consisted of 31 healthy volunteers with no history of heart disease and no reactive serology for Chagas disease. Baseline ECG was performed in all subjects. The Selvester scoring method was performed according to the standardized guide (< 3 points: no myocardial injury,> 3: points × 3% = % of the predicted LV infarction).Results: A total of 62 subjects were included, 31 as cases and 31 as controls. The mean follow-up of the case group was 17 months. The control group presented normal ECG. The case group presented 13 alterations before treatment and 11 after. Nineteen individuals presented scores > 3 points, 6 before and 13 after. In 19.36% of subjects, myocardial injury was found before treatment and in 41.94% after treatment.Conclusion: This is the first study that uses the Selvester score (SS) to predict myocardial injury in subjects with ACD. The results of this study suggest the significant presence of myocardial injury from the beginning of treatment to the period post treatment of ACD, which demonstrates that the SS can be applied for stratification and follow-up of Chagas disease in the Amazon region. [ABSTRACT FROM AUTHOR]

Background: Chagas disease is endemic in Latin America and, over the last few decades, due to population movements, the disease has spread to other continents. Early diagnosis and treatment are critical in terms of improving outcomes for those living with Chagas disease. However, poor knowledge and awareness is one of barriers that affects access to Chagas disease diagnosis and treatment for the population at risk. Information regarding immigrants' knowledge concerning Chagas disease control and prevention is insufficient in non-endemic countries and, therefore, this study sought to assess Chagas disease knowledge and awareness within the Bolivian community residing in Madrid. Methods: This cross-sectional study was carried out in March–August 2017. A total of 376 Bolivians answered a structured questionnaire. A knowledge index was created based on respondents' knowledge about transmission, symptoms, diagnosis, and place to seek treatment. Multivariate logistic regressions analyses were performed to assess the factors associated with respondents' knowledge of Chagas disease. Results: A total 159 (42.4%) of Bolivians interviewed about their knowledge of Chagas disease were men and 217 (57.6%) were women. Vinchuca was mentioned as mode of transmission by 71% of the Bolivians surveyed, while only 9% mentioned vertical transmission. Almost half of the Bolivians did not know any symptom of Chagas disease and only 47% knew that a specific blood test is necessary for diagnosis. Most of Bolivians were aware of the severity of Chagas disease, but 45% of Bolivians said that there is no cure for Chagas and 96% did not know any treatment. Based on the index of knowledge generated, only 34% of Bolivians had a good knowledge about Chagas disease transmission, symptoms, diagnosis and treatment. According to the multiple logistic regression analysis, knowledge regarding Chagas disease, diagnosis and treatment was significantly higher amongst older Bolivians who had secondary education at least, as well as amongst those who had already been tested for Chagas disease. Conclusions: This study found that most of the Bolivian population living in Spain had poor knowledge about Chagas disease transmission, symptoms, diagnostic methods and treatment. A poor understanding of the disease transmission and management is one of the most important barriers when it comes to searching for early diagnosis and appropriate care. [ABSTRACT FROM AUTHOR]

Trypanosoma cruzi is a zoonotic parasite endemic in the southern US and the Americas, which may frequently infect dogs, but limited information is available about infections in cats. We surveyed a convenience sample of 284 shelter cats from Southern Louisiana to evaluate T. cruzi infection using serological and PCR tests. Parasites from PCR positive cats were also genotyped by PCR and deep sequencing to assess their genetic diversity. We detected a seropositivity rate for T. cruzi of at least 7.3% (17/234), and 24.6% of cats (70/284) were PCR positive for the parasite. Seropositivity increased with cat age (R2 = 0.91, P = 0.011), corresponding to an incidence of 7.2% ± 1.3 per year, while PCR positivity decreased with age (R2 = 0.93, P = 0.007). Cats were predominantly infected with parasites from TcI and TcVI DTUs, and to a lesser extent from TcIV and TcV DTUs, in agreement with the circulation of these parasite DTUs in local transmission cycles. These results indicate that veterinarians should have a greater awareness of T. cruzi infection in pets and that it would be important to better evaluate the risk for spillover infections in humans. [ABSTRACT FROM AUTHOR]

Background: Triatoma garciabesi, a potential vector of the parasitic protozoan Trypanosoma cruzi, which is the causative agent of Chagas disease, is common in peridomestic and wild environments and found throughout northwestern and central Argentina, western Paraguay and the Bolivian Chaco. Genetic differentiation of a species across its range can help to understand dispersal patterns and connectivity between habitats. Dispersal by flight is considered to be the main active dispersal strategy used by triatomines. In particular, the morphological structure of the hemelytra is associated with their function. The aim of this study was to understand how genetic diversity is structured, how morphological variation of dispersal-related traits varies with genetic diversity and how the morphological characteristics of dispersal-related traits may explain the current distribution of genetic lineages in this species., Methods: Males from 24 populations of T. garciabesi across its distribution range were examined. The cytochrome c oxidase I gene (coI) was used for genetic diversity analyses. A geometric morphometric method based on landmarks was used for morpho-functional analysis of the hemelytra. Centroid size (CS) and shape of the forewing, and contour of both parts of the forewing, the head and the pronotum were characterised. Length and area of the forewing were measured to estimate the aspect ratio., Results: The morphometric and phylogenetic analysis identified two distinct lineages, namely the Eastern and Western lineages, which coincide with different ecological regions. The Eastern lineage is found exclusively in the eastern region of Argentina (Chaco and Formosa provinces), whereas the Western lineage is prevalent in the rest of the geographical range of the species. CS, shape and aspect ratio of the hemelytra differed between lineages. The stiff portion of the forewing was more developed in the Eastern lineage. The shape of both portions of the hemelytra were significantly different between lineages, and the shape of the head and pronotum differed between lineages., Conclusions: The results provide preliminary insights into the evolution and diversification of T. garciabesi. Variation in the forewing, pronotum and head is congruent with genetic divergence. Consistent with genetic divergence, morphometry variation was clustered according to lineages, with congruent variation in the size and shape of the forewing, pronotum and head., (© 2024. The Author(s).)

Background: Increased Attalea butyracea palm propagation, notable for its role as key habitat for the primary Chagas disease vector in Panama, has been linked to landscape disturbance in single-palm observations in this region. Close proximity of these palms to human dwellings is proposed to increase risk of Chagas disease transmission from sylvatic transmission cycles to domestic transmission involving human populations. This study examines the relationship between landscape disturbance and mature A. butyracea spatial distribution, density, and proximity to human populations and vector and reservoir species' movement corridors at a regional scale in a 300 km2 heterogeneous tropical landscape in central Panama. Methods: We remotely identified the locations of over 50,000 mature A. butyracea palms using high-resolution WorldView2 satellite imagery. A local Getis-Ord Gi* spatial analysis identified significant clusters of aggregated palms. Associations between palm and cluster abundance and a landscape disturbance gradient, derived from official Panama land cover data, were tested using Chi-square tests for Homogeneity and Z-test for proportions. Kruskall-Wallis non-parametric analysis of variance tests were run to assess whether palm cluster area varied by disturbance level, or whether disturbance was associated with proximity of palms and palm clusters to susceptible populations or vector movement corridors. Results: Our findings indicate a regional relationship between landscape disturbance and A. butyracea occurrence. We observe a significant increase in both individual and clustered A. butyracea in secondary forest, but a reduction of palms in agricultural settings. We do not detect evidence of any reduction in abundance of palms in residential settings. The majority of residential and commercial buildings in our study area are within vector flight distance of potential vector habitat in palm crowns. Conclusions: We observe probable anthropogenic elimination of A. butyracea palms in agricultural, but not residential, settings. Even in heavily deforested regions, significant concentrations of mature palms remain in close proximity to human establishments. [ABSTRACT FROM AUTHOR]

Background: Trypanosoma cruzi - the causative agent of Chagas disease - is known to circulate in commensal pests, but its occurrence in urban environments is not well understood. We addressed this deficit by determining the distribution and prevalence of T. cruzi infection in urban populations of commensal and wild rodents across New Orleans (Louisiana, USA). We assessed whether T. cruzi prevalence varies according to host species identity and species co-occurrences, and whether T. cruzi prevalence varies across mosaics of abandonment that shape urban rodent demography and assemblage structure in the city. Methods: Leveraging city-wide population and assemblage surveys, we tested 1428 rodents comprising 5 species (cotton rats, house mice, Norway rats, rice rats and roof rats) captured at 98 trapping sites in 11 study areas across New Orleans including nine residential neighborhoods and a natural area in Orleans Parish and a neighborhood in St. Bernard Parish. We also assayed Norway rats at one site in Baton Rouge (Louisiana, USA). We used chi-square tests to determine whether infection prevalence differed among host species, among study areas, and among trapping sites according to the number of host species present. We used generalized linear mixed models to identify predictors of T. cruzi infection for all rodents and each host species, respectively. Results: We detected T. cruzi in all host species in all study areas in New Orleans, but not in Baton Rouge. Though overall infection prevalence was 11%, it varied by study area and trapping site. There was no difference in prevalence by species, but roof rats exhibited the broadest geographical distribution of infection across the city. Infected rodents were trapped in densely populated neighborhoods like the French Quarter. Infection prevalence seasonally varied with abandonment, increasing with greater abandonment during the summer and declining with greater abandonment during the winter. Conclusions: Our findings illustrate that T. cruzi can be widespread in urban landscapes, suggesting that transmission and disease risk is greater than is currently recognized. Our findings also suggest that there is disproportionate risk of transmission in historically underserved communities, which could reinforce long-standing socioecological disparities in New Orleans and elsewhere. [ABSTRACT FROM AUTHOR]