Citizen science to complement the surveillance of Triatominae (Hemiptera: Reduviidae) with data of Trypanosoma cruzi (Kinetoplastea: Trypanosomatidae) infection and spatial distribution models in northeast Mexico.

Described by the Brazilian scientist Carlos Chagas more than a century ago, Chagas disease (ChD) currently affects 8 to 10 million persons and causes more than 10 000 deaths each year.[1][1] Originally confined to Latin American countries, ChD had been considered an exotic disease and received less

Chagas disease is a major vector-borne parasitic disease in Latin America, primarily transmitted to humans by triatomine vectors. Non-domiciliated triatomine species such as Triatoma dimidiata in the Yucatan peninsula, Mexico, can transiently invade houses and are emerging as a major challenge to control Trypanosoma cruzi transmission to humans. We analyzed the spatio-temporal spreading of house infestation by T. dimidiata in four rural villages. Triatomines were collected in four rural villages over a 2 years period, and the spatio-temporal patterns of infestation were analyzed. Triatomines were consistently more abundant at the periphery of villages than in centers, indicating a much higher risk of T. cruzi transmission at the periphery. Male T. dimidiata were found further in the center of the village, while females remained closer to the periphery, suggesting differential dispersal capabilities between sexes, although the timing of dispersal appeared identical. Surprisingly, infected females were consistently collected in houses much further from the surrounding bushes than non-infected females, while the distribution of males was unaffected by their T. cruzi infection status, suggesting an increased dispersal capability in infected females. The spatial structure of infestation should be taken into account for the prioritization of vector control activities within villages, and spatially targeted interventions may be explored. A potential vector manipulation by T. cruzi, observed for the first time in triatomines, may favor parasite transmission to new hosts.

Dear Sir, We read the article “Reactivation of Chagas disease after a bone marrow transplant in Italy: first case report” by Angheben et al1. It is well known that Chagas disease, caused by a protozoa, Trypanosoma cruzi, is an autochthonous disease with a widespread distribution from the south of the United States to Mexico and South America. The disease can also affect people in Europe with its presence related to migratory flows. In non-endemic countries, Chagas disease can be acquired by congenital transmission, blood transfusion and organ transplantation. Transfusion is considered the second most common mode of transmission for T. cruzi; it is estimated that approximately 10–20% of blood from chronically infected donors is infective considering that T. cruzi remains viable in stored whole blood and citrated blood samples stored at refrigerator and room temperatures, respectively. Furthermore, it is known that this disease can be fatal, especially in immunosuppressed patients2, following reactivation of latent infections. The most common symptoms of Chagas disease reactivation are both cardiac and gastrointestinal manifestations. Most of the infected people are not aware of their status because the disease frequently causes few or no symptoms during the acute phase and evolves commonly to a clinically silent phase. Several cases of acute Chagas disease following solid organ and bone marrow transplantation have been described in the past. The first case of Chagas disease reactivation after a bone marrow transplant recorded in Italy is of great interest: the case was a 9-year old Argentinean girl with a diagnosed acute lymphoblastic leukaemia1. The authors of the case report hypothesised that a probable cause of reactivation of Chagas disease in the patient could have been immunosuppression secondary to the bone marrow transplant and Graft-versus-Host disease prophylaxis (cyclosporine A and a short course of methotrexate). In accordance with this hypothesis, there is another report of immunosuppression associated with cord blood transplantation seeming to be responsible for the fatal outcome of Chagas disease in a 25-year old male with high-risk acute myeloid leukemia3. Immunosuppression, which has become an increasingly relevant clinical condition in the last 50 years, modifies the natural history of several diseases, including T. cruzi infection: patients become predisposed to the development or reactivation of opportunistic infections with particular and often severe clinical outcomes. Several guidelines for the treatment of immunosuppressed patients with Chagas disease have been published recently, but there is no international consensus on the management of reactivation in these patients. In cases of reactivation, early anti-parasitic treatment with benznidazole and/or nifurtimox has proven to be highly effective and posaconazole should be indicated when these fail. Importantly, little is known about the relationship between the incidence of neoplastic disease and T. cruzi infection, or about whether the immune response, induced by this infection, modifies the development or localisation of neoplasms. Based on clinical observations in immunosuppressed patients some authors have speculated that benznidazole treatment might actually cause neoplasms. The relationship between immunosuppression and neoplastic disease in patients with T. cruzi infection has been analysed from three perspectives as reported by Pinazo et al.4: (i) neoplastic disease as a potentially immunosuppressive condition that increases the likelihood of reactivation of infections; (ii) neoplastic disease occurring as a result of treatment with benznidazole, either alone or in combination with immunosuppressive drugs; and (iii) neoplastic disease as a condition that is potentially more common in patients with Chagas disease. Clinical studies with long-term follow-up have found no evidence of a higher incidence of histological signs of malignancy with immunosuppressive therapy, concluding that benznidazole and its association with other immunosuppressive drugs do not contribute to an increased incidence of neoplastic disease4. However, reactivation of T. cruzi infection must be considered in patients with chronic Chagas disease and neoplastic diseases requiring intensive and/or long-term pharmacological immunosuppression4. Currently, it is not easy to make general evidence-based recommendations for the management of T. cruzi-infected patients or for the prevention of reactivation. Clinicians should bear in mind that the natural course of T. cruzi infection can be modified by other diseases or their treatment. Furthermore, there have been no reports of a relationship between Chagas disease reactivation and other immunosuppressive drugs used in the treatment of systemic autoimmune diseases and it has not been shown that these diseases have a direct role in the progression of T. cruzi infection. The main goal in T. cruzi-infected patients with an immunosuppressive condition could be to prevent reactivation by close monitoring. To do this, an early diagnosis of T. cruzi infection in immunosuppressed individuals is extremely important and should be considered prior to immunosuppressive treatment. For this reason, investigations for parasitaemia, detectable by Strout or quantitative buffy coat testing or microhaematocrit methods, are recommended, especially in immunosuppressed patients during follow-up. The only effective form of prevention for T. cruzi infection would be to avoid the use of blood or organs from donors who come from countries where Chagas disease is endemic or to perform serological screening for T. cruzi on these donors. Chagas disease is considered an emerging problem in Italy5. Since chronic T. cruzi infection is often asymptomatic, most infected organ donors will not have a known history of the disease and laboratory screening is essential. Although there is already some infrastructure at a national level5, there is not yet a systematic programme of reference centres for neglected diseases. Thus, Italy should implement a national network to prevent donations of blood and/or organs from T. cruzi-infected donors, improving the access to diagnosis. In addition, an infrastructure that ensures detection and treatment of acute and chronic cases, as well as congenital infections, should be developed. In conclusion, it is important to extend epidemiological programmes to control Chagas disease in blood donors, stem cell donors and recipients by serological screening, in order to prevent adverse outcomes, especially in immunosuppressed patients.

BackgroundVector infection prevalence is a key component of vectorial capacity and transmission risk. Optical microscopy observation (OM) of fecal drops has been the classic method for detecting Trypanosoma cruzi infection in triatomine bugs until the advent of polymerase chain reaction (PCR)-based techniques. However, agreement among OM- and PCR-based techniques has been highly heterogeneous.MethodsWe used hierarchical site-occupancy models accounting for imperfect detection to estimate method-specific detection probabilities of T. cruzi infection in field-collected Triatoma infestans and to assess whether T. cruzi infection varied with triatomine developmental stage and collection ecotope. We also performed a scoping review of the literature on comparisons between OM and PCR for T. cruzi infection diagnosis in triatomines. Triatomines were collected before vector control interventions in Pampa del Indio houses (Argentine Chaco) and examined by OM. We amplified the variable regions of the kinetoplastid minicircle genome (vkDNA-PCR) in DNA extracted from the rectal ampoules of 64 OM-positive and 65 OM-negative T. infestans.ResultsvkDNA-PCR detected T. cruzi infection in 59 (92.2%) OM-positive bugs and in 19 (29.2%) OM-negative triatomines in blind tests. The overall prevalence of infection, as determined by a positive test result by either vkDNA-PCR or OM, was 64.3% [95% confidence interval (95% CI) 55.8–72.1%]. Detection probability of T. cruzi infection by vkDNA-PCR (92%, 95% CI 83–97%) was substantially higher than for OM (76%, 95% CI 65–84%). Infection was minimal (26.2%) in peridomestic nymphs and maximal in domestic adult triatomines (81.7%). In the literature review encompassing 26 triatomine species from 11 countries, inter-method agreement ranged from 28.6% to 100%. The lowest agreement was observed in Rhodnius sp. and Panstrongylus lutzi and the highest among Triatoma sp., with wide variability in the protocols and outcomes of molecular diagnosis in comparison with OM.ConclusionsOur study provides a synthesis on the different sources (both biological and technical) of variation of the outcomes of OM- and PCR-based diagnosis of T. cruzi infection in triatomines and identifies new research needs for diagnostic improvement.Graphical

Cytokine modulation, oxidative stress and thymic dysfunctions: Role of age-related changes in the experimental Trypanosoma cruzi infection: Age-related thymic dysfunctions and Trypanosoma cruzi infection

Chagas Disease Recommendations for Solid-Organ Transplant Recipients and Donors.

International migration has changed the global distribution of Chagas disease, with the emerging importance of non-endemic regions. We aimed at better documenting the Australia and New Zealand risk of Chagas disease and needs for interventions. We reviewed Chagas disease-related evidences, policies and practices in Australia and New Zealand and calculated the estimated prevalence. Australia hosts a rapidly growing population at risk and had 1928 infected residents in 2011; New Zealand had 98 in 2006. These figures underestimate the real situation, as they do not consider non-permanent residents. The only existing policy in both countries is the identification of blood donors with a history of or a risk of infection via questionnaire. There is no programme of detection and care of patients. The lifetime economic burden of disease for society is potentially very high. Chagas disease is an emerging health risk with potential high human and economic costs in Australia and New Zealand in the absence of public health attention. Implementing strategies to screen high-risk groups and prevent transmission should be considered. Moreover, migration between the Western Pacific and Chagas endemic regions and the presence of vectors means this risk applies in the whole region.

Trypanosoma cruzi is the parasite responsible for Chagas disease (CD), that affects 6-8 million people worldwide. CD treatment is limited to two drugs (benznidazole and nifurtimox). Treatment is mostly effective during the acute phase of the disease (initial two months post-infection), while their efficacy during the chronic phase is controversial. In the absence of treatment, 30% of infected individuals suffer irreversible chronic cardiac and digestive damages, which lead to inability and, in some instances, death. Patients with Laron Syndrome (LS, a form of congenital GH insensitivity) are short in stature with low levels of IGF-1, elevated levels of GH and, surprisingly, are resistant to cancer and diabetes. A cohort of LS patients living in southern Ecuador, where CD is endemic, has been studied by Dr. Jaime Guevara for over 25 years (1). Few, if any, cases of CD have been reported among these patients (Dr. Guevara, personal communications). T. cruzi infection has been shown to directly modulate pituitary hormones such as GH, PRL and glucocorticoids (stress related hormones), leading to immunosuppression and thymic atrophy by depletion of CD4+ CD8+ cells. Previously, rats infected with T. cruzi and treated with GH showed reduced parasitism and less tissue damage compared to controls (2). The purpose of this research is to investigate the in vitro effect of GH during T. cruzi infection, simulating conditions of GH insensitivity. First, we separately treated T. cruzi and the host cells [human cervical cancer cell line (HeLa) and male mouse fibroblast (L-cells)] with relatively low or high levels of GH, IGF-1, PRL, and EGF. Next, we treated the parasite and host cells simultaneously with these hormones. When the parasites were treated alone, T. cruzi responded to exogenous GH (5ng/ml-50ng/ml) by significantly increasing the percentage of amastigotes (less infective form of the parasite). Also, when GH (50ng/ml) were administered to the host cells, T. cruzi infectivity was significantly reduced by 12% (percentage of infection) compared to 20% from untreated conditions. Similarly, both parasite and host cells treated with GH significantly reduced T. cruzi infectivity (10%) compared to untreated conditions (18%). We further treated both cell lines with a combination of GH/IGF-1. Conditions used were as follows: control (no-treatment), moderate levels (5ng/ml GH+150 ng/ml IGF-1), relatively high levels (50ng/ml GH+600ng/ml IGF-1), or levels that would simulate those found in patients with LS(50ng/ml GH+20 ng/ml IGF-1). Of these, the LS concentrations significantly reduced infection in both cell lines (11%) compared to control (16%). Together these results indicate that GH can influence T. cruzi infectivity and that GH, not IGF-1, is mediating the decreased infectivity. Finally, the results suggest that high concentrations of GH, as seen in LS patients, could be protective during T. cruzi infection.1)Guevara-Aguirre et al., 2011 2) Frare et al., 2010

BackgroundThe highly complex and largely neglected Chagas disease (CD) has become a global health problem due to population movements between Latin America and non-endemic countries, as well as non-vectorial transmission routes. Data on CD testing and treatment from routine patient care in Germany of almost two decades was collected and analysed.MethodsGerman laboratories offering diagnostics for chronic Trypanosoma cruzi (T. cruzi) infection in routine patient care were identified. All retrievable data on tests performed during the years of 2000–2018 were analysed. Additional clinical information regarding patients diagnosed with CD was collected through questionnaires.ResultsFive German laboratories with diagnostics for T. cruzi infection in routine patient care were identified. Centres in Hamburg and Munich offered two independent serological tests to confirm the CD diagnosis, as recommended by WHO during the entire time period 2000–2018. Overall, a total of n = 10,728 independent tests involving n = 5991 individuals were identified with a progressive increase in testing rates over time, only n = 130 (16.0%) of the tested individuals with known nationality came from CD endemic countries. Of all test units conducted at the included institutes, a total of n = 347/10,728 (3.2%) tests on CD were positive, of which n = 200/347 (57.6%) were ELISA, n = 133/347 (38.3%) IFT, n = 10/347 (2.9%) PCR, and n = 4/347 (1.2%) RDT. Of the n = 5991 individuals only n = 81 (1.4%) with chronic infection were identified, n = 52 females and n = 28 males. Additional clinical information could only be collected from n = 47.ConclusionThe results of this study give insight into the deployment of screening, detection, diagnosis, and treatment of T. cruzi over the last two decades in Germany and existing deficits therein; the creation of guidelines for Germany could be a step forward to improve the existing gaps.

Event Abstract Back to Event Role of arachidonic acid metabolites in Trypanosoma cruzi infection Néstor A. Guerrero1, Manuel Fresno1 and Núria Gironès1* 1 Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Spain Cardiac inflammation plays an important role in the pathophysiology of Chagas disease, caused by Trypanosoma cruzi. Lipid mediators derived from arachidonic acid (AA), like prostaglandins and leukotrienes, are considered regulators of homeostasis and inflammation. These molecules are produced by a biosynthetic pathway controlled by enzymes as cyclooxygenases and lipoxygenases. The role of cyclooxygenase-2 (COX-2) in immunosuppression during the acute phase of T. cruzi infection has been described using non-steroidal anti-inflammatory drugs, which are inhibitors of this enzyme. In this study, we first investigated the expression of enzymes involved in AA metabolism during T. cruzi infection. Susceptible and non-susceptible mouse models of infection were used to further analyze the role of lipid mediators in T. cruzi infection. Our results confirm the expression of several of these enzymes in T. cruzi-infected heart, in particular COX-2. CD68+ heart-infiltrating macrophages were the major cell type expressing COX-2. CD11b+ heart-infiltrating myeloid cells were purified and they were able to produce prostaglandins PGE2 and PGF2α. Studies using gene-deficient mouse models indicated that regulation of COX-2 and PGE2, through PGE2 receptor 2 signaling, was in part responsible of cardiac inflammation in T. cruzi infection. The key role of lipid mediators in Chagas disease inflammation and the availability of drugs that inhibit their synthesis and their receptors could be useful for the treatment of this neglected disease. Acknowledgements This work was supported by grants: SAF2007-61716, SAF2005-02220, PS09/00538, RECAVA RD06/0014/1013, RICET RD06/0021/0016, HEALTH-FE-2008-22303,ChagasEpiNet, CC08-UAM/SAL-4440/08, AECID A/025417/09 and ‘‘Fundacion Ramon Areces". M. Fresno and N. Girones are professors at the UAM. N.A.G. was a recipient of a fellowship from ISCIII and RICET. We thank Beatriz Barrocal, Maria A. Chorro, M.C. Maza and Carlos Chillon for their technical assistance. Keywords: Trypanosoma cruzi, Cyclooxigenase-2, Prostaglandin E2 receptor 2, Cardiac inflammation, in vivo infection Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Host-pathogen interactions Citation: Guerrero NA, Fresno M and Gironès N (2013). Role of arachidonic acid metabolites in Trypanosoma cruzi infection. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01131 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Jul 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Núria Gironès, Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, 28049, Spain, ngirones@cbm.csic.es Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Néstor A Guerrero Manuel Fresno Núria Gironès Google Néstor A Guerrero Manuel Fresno Núria Gironès Google Scholar Néstor A Guerrero Manuel Fresno Núria Gironès PubMed Néstor A Guerrero Manuel Fresno Núria Gironès Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Chagas disease (CD) is a highly prevalent parasitic disease in immigrants from Mexico, as well as all of Central and South America. The total number of infected people is estimated between eight and ten million [1], [2], of whom 30%–40% either have, or will, develop cardiopathy, gastrointestinal disease, or both [1]. Cardiac involvement is the main cause of death from this infection through arrhythmias and cardiomyopathy. Nifurtimox and benznidazole are the only available medicines with proven efficacy against Trypanosoma cruzi infection in acute, congenital infection and early chronic infection. Until recently the treatment of chronic disease, particularly of adult patients with indeterminate form, was controversial; but during the past decade there has been a trend to offer treatment to adult patients and those with early cardiomyopathy [3]. To understand the magnitude of the problem, some economic studies have calculated the global cost of the disease worldwide at around 7,200,000,000 American dollars per year [4], which is mainly due to cardiovascular disease and early mortality. This cost is similar to, or even higher than, other prominent conditions such as rotavirus disease or cervical cancer [4]. In endemic countries, the main transmission route to humans is vectorial transmission through the faeces of infected triatomine bugs [1]. Oral transmission also occurs in endemic countries when beverages or food are contaminated with triatomine faeces [5]. Transmission through blood transfusion, organ transplantation from an infected donor, or from mother to child are less common routes, although they are of increasing importance, particularly in nonendemic areas where vectorial and oral transmission do not occur [1]. Another sporadic route of transmission is through the syringe sharing among drug users [6]. During the past decade, the infection has become a public health problem in some nonendemic countries, mainly due to migration and the chronic carriage of T. cruzi infection among a proportion of immigrants from endemic Latin American countries [7]. Since the first report of a case of CD in Europe was published in 1981 [8], sporadic cases have been detected in different European countries [9]. Since 2000, the number of reported cases has alarmingly increased, particularly in Spain and, to a lesser extent, in Italy and Switzerland [9]–[15]. In Europe, the currently estimated number of people with CD is between 68,000 and 122,000, but by 2009 only 4,290 had been diagnosed (index of underdiagnosis 93.9%–96.4%) [16]. The risk of transmission of T. cruzi infection in nonendemic countries through blood transfusion and organ transplantation has been described in multiple studies in the USA and more recently in Europe [17]–[21]. Moreover, several confirmed cases of T. cruzi transmission have already been detected in Europe [9], [22]. Accordingly, some studies have shown that it is cost-effective to screen for T. cruzi infection at blood banks, but depending on the prevalence of the disease, a mass screening of subjects—testing all—or a more selected strategy with screening questions to determine the risk level—screening and testing—should be applied [23]. Regarding congenital transmission, several studies have reported a rate of seroprevalence in Europe from 1.53% to 9.7% in pregnant women with the Bolivian population showing the highest seroprevalence rate [10], [24], [25], and with a transmission rate to newborn of around 7.3% [10]. Moreover, the strategy of screening pregnant women to control and treat newly diagnosed infected newborns has also shown to be cost-effective [26]. In response, several nongovernmental and later governmental initiatives have developed strategies to tackle this public health problem in the last years. The main aim of these initiatives has been to control the main transmission routes in nonendemic countries. Accordingly, some European countries have implemented national or regional measures to control transmission [27], [28], but many countries still have no legislation about it. In 2009, the World Health Organization (WHO) convened a WHO informal consultation (jointly organized by WHO headquarters and the WHO Regional Office for Europe) that performed a comprehensive review outlining this specific issue in Europe [29]. In collaboration with WHO, a research group working on migrant health, COHEMI, (COordinating resources to assess and improve HEalth status of MIgrants from Latin America) has undertaken this study aimed at reviewing the health policies implemented in European Union countries with the highest disease prevalence, plus Switzerland, to control the transmission of CD through blood transfusion, organ transplantation, and the congenital route.

BackgroundWe evaluate the association between Trypanosoma cruzi infection and strongyloidiasis in a cohort of Latin American (LA) migrants screened for both infections in a non-endemic setting.MethodologyCase-control study including LA individuals who were systematically screened for T. cruzi infection and strongyloidiasis between January 2013 and April 2015. Individuals were included as cases if they had a positive serological result for Strongyloides stercoralis. Controls were randomly selected from the cohort of individuals screened for T. cruzi infection that tested negative for S. stercoralis serology. The association between T. cruzi infection and strongyloidiasis was evaluated by logistic regression models.Principal findingsDuring the study period, 361 individuals were screened for both infections. 52 (14.4%) individuals had a positive serological result for strongyloidiasis (cases) and 104 participants with negative results were randomly selected as controls. 76 (48.7%) indiviuals had a positive serological result for T. cruzi. Factors associated with a positive T. cruzi serology were Bolivian origin (94.7% vs 78.7%; p = 0.003), coming from a rural area (90.8% vs 68.7%; p = 0.001), having lived in an adobe house (88.2% vs 70%; p = 0.006) and a referred contact with triatomine bugs (86.7% vs 63.3%; p = 0.001). There were more patients with a positive S. stercoralis serology among those who were infected with T. cruzi (42.1% vs 25%; p = 0.023). Epidemiological variables were not associated with a positive strongyloidiasis serology. T. cruzi infection was more frequent among those with strongyloidiasis (61.5% vs 42.3%; p = 0.023). In multivariate analysis, T. cruzi infection was associated with a two-fold increase in the odds of strongyloidiasis (OR 2.23; 95% CI 1.07–4.64; p = 0.030).ConclusionsT. cruzi infection was associated with strongyloidiasis in LA migrants attending a tropical diseases unit even after adjusting for epidemiological variables. These findings should encourage physicians in non-endemic settings to implement a systematic screening for both infections in LA individuals.

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

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

BackgroundPeri-urban and urban settings have recently gained more prominence in studies on vector-borne transmission of Trypanosoma cruzi due to sustained rural-to-urban migrations and reports of urban infestations with triatomines. Prompted by the finding of Triatoma infestans across the rural-to-urban gradient in Avia Terai, an endemic municipality of the Argentine Chaco, we assessed selected components of domestic transmission risk in order to determine its variation across the gradient.MethodsA baseline vector survey was conducted between October 2015 and March 2016, following which we used multistage random sampling to select a representative sample of T. infestans at the municipal level. We assessed T. cruzi infection and blood-feeding sources of 561 insects collected from 109 houses using kinetoplast DNA-PCR assays and direct enzyme-linked immunosorbent assays, respectively. We stratified triatomines according to their collection site (domestic or peridomestic), and we further categorized peridomestic sites in ecotopes of low- or high-risk for T. cruzi infection.ResultsThe overall adjusted prevalence of T. cruzi-infected T. infestans was 1.8% (95% confidence interval [CI] 1.3–2.3) and did not differ between peri-urban (1.7%) and rural (2.2%) environments. No infection was detected in bugs captured in the urban setting; rather, infected triatomines were mainly collected in rural and peri-urban domiciles, occurring in 8% of T. infestans-infested houses. The main blood-feeding sources of domestic and peridomestic triatomines across the gradient were humans and chickens, respectively. The proportion of triatomines that had fed on humans did not differ between peri-urban (62.5%) and rural (65.7%) domiciles, peaking in the few domestic triatomines collected in urban houses and decreasing significantly with an increasing proportion of chicken- and dog- or cat-fed bugs. The relative odds ratio (OR) of having a T. cruzi infection was nearly threefold higher in bugs having a blood meal on humans (OR 3.15), dogs (OR 2.80) or cats (OR: 4.02) in a Firth-penalized multiple logistic model.ConclusionsTrypanosoma cruzi transmission was likely occurring both in peri-urban and rural houses of Avia Terai. Widespread infestation in a third of urban blocks combined with high levels of human–triatomine contact in the few infested domiciles implies a threat to urban inhabitants. Vector control strategies and surveillance originally conceived for rural areas should be tailored to peri-urban and urban settings in order to achieve sustainable interruption of domestic transmission in the Chaco region.Graphical