Cardiac damage during the acute phase of Chagas disease (CD) is associated with an increase in pro-inflammatory markers and oxidative stress. Melatonin (MEL) has emerged as a promising therapy for CD due to its antioxidant and immunomodulatory properties; however, the protective action of MEL in the cardiac tissue, as well as its direct action on the parasite cycle, is not fully understood. We investigated the effects of MEL on heart parasitism in mice infected with Trypanosoma cruzi and also its effects on the parasitic proliferation in vitro. Our in vivo study showed that MEL reduced circulating parasitemia load, but did not control tissue (heart, liver, and spleen) parasitism in mice. MEL did not prevent the redox imbalance in the left ventricle of infected mice. Our in vitro findings showed that MEL did not inhibit parasites replication within cells, but rather increased their release from cells. MEL did not control parasitism load in the heart or prevent the cardiac redox imbalance induced by acute T. cruzi infection. The hormone controlled the circulating parasitic load, but within cells MEL accelerated parasitic release, a response that can be harmful.

Chagas disease is a zoonotic, parasitic, vector-borne neglected tropical disease that affects the lives of over 6 million people throughout the Americas. Trypanosoma cruzi, the causative agent, presents extensive genetic diversity. Here we report the genome sequence of reference strain SC43cl1, a hybrid strain belonging to the TcV discrete typing unit (DTU). The assembled diploid genome was 79 Mbp in size, divided into 1236 contigs with an average coverage reaching 180×. There was extensive synteny of SC43cl1 genome with closely related TcV and TcVI genomes, with limited sequence rearrangements. TcVI genomes included several expansions not present in TcV strains. Comparative analysis of both nuclear and kinetoplast sequences clearly separated TcV from TcVI strains, which strongly supports the current DTU classification.

To analyse spatial patterns and the temporal tendency of mortality related to Chagas disease, in order to identify priority control areas in the state of Sergipe, Northeast Brazil.
We conducted an ecological and time-series study with spatial analysis techniques on deaths from Chagas disease in the state of Sergipe (1996-2016). We used data from the Mortality Information System (SIM). The temporal analysis was performed using a statistical technique capable of describing changes in the trend pattern for the period. Thematic maps were elaborated from point and polygonal analyses.
There were 247 deaths related to Chagas disease, with a mean of 11.7 deaths/year, most of them male (64%), and aged 50-59 years (21%) and 60-69 years (26%). Two segments with increasing, non-constant and significant trends were identified: 1996-2005 (APC = 21.6%; P = 0.01) and 2005-2016 (APC = 4.4%; P = 0.01), with APPC = 11.8% (P = 0.01). A positive and significant spatial autocorrelation with areas of higher risk of death was found in the southern region of the state.
The trend of mortality related to Chagas disease in the state of Sergipe was increasing during the period analysed, with a heterogeneous distribution of cases. A main risk area was identified in the southern region of the state.
Analyser les profils spatiaux et la tendance temporelle de la mortalité liée à la maladie de Chagas, afin d\'identifier les domaines de priorité de lutte dans l\'Etat de Sergipe, dans le nord-est du Brésil. MÉTHODES: Nous avons mené une étude écologique et de séries chronologiques avec des techniques d\'analyse spatiale sur les décès dus à la maladie de Chagas dans l\'état de Sergipe (1996-2016). Nous avons utilisé les données du système d\'information sur la mortalité (SIM). L\'analyse temporelle a été réalisée à l\'aide d\'une technique statistique capable de décrire les changements dans le profil de tendance pour la période. Des cartes thématiques ont été élaborées à partir d\'analyses ponctuelles et polygonales. RÉSULTATS: Il y a eu 247 décès liés à la maladie de Chagas, avec une moyenne de 11,7 décès/an, pour la plupart de sexe masculin (64%), et âgés de 50 à 59 ans (21%) et de 60 à 69 ans (26%). Deux segments avec des tendances à la hausse, non constantes et significatives ont été identifiés: 1996-2005 (APC = 21,6%; p = 0,01) et 2005-2016 (APC = 4,4%; p = 0,01), avec APPC = 11,8% (p = 0,01). Une autocorrélation spatiale positive et significative avec des zones à haut risque de décès a été trouvée dans la région sud de l\'Etat.
La tendance de la mortalité liée à la maladie de Chagas dans l\'état de Sergipe a augmenté au cours de la période analysée , avec une répartition hétérogène des cas. Une principale zone à risque a été identifiée dans la région sud de l\'Etat.

To estimate the prevalence of Chagas disease in pregnant women and the vertical transmission of the disease.
Observational studies were identified from eight electronic databases, and details on study design, population and prevalence of Chagas disease were extracted. The data were pooled using a random-effects model, and choropleth maps were created based on geopolitical regions and countries.
The search identified 7788 articles, of which 50 were eligible. We observed a 9% prevalence of Chagas disease among pregnant women in the Americas (95% confidence interval [CI]: 8-10, I2  = 99.96%). High disease prevalence was identified in pregnant women in South American countries (12%, 95% CI: 11-13), while lower values were identified in pregnant women in North America (2%, 95% CI: 1-3). Countries with medium Human Development Index (HDI) had a higher prevalence of Chagas disease in pregnant women (15%, 95% CI: 13-16, I2  = 99.98%) than countries with high HDI (3%, 95% CI: 2-3). The rate of vertical transmission in the continent was 2% (95% CI: 1-2). The statistical analysis showed that this heterogeneity was explained by the study design, region of the Americas and mean income of the country.
South and Central American countries have a high prevalence and vertical transmission of Chagas disease. Therefore, systematic screens for this disease during the prenatal period are necessary in addition to the diagnosis and treatment of children at risk for Trypanosoma cruzi infection.
Estimer la prévalence de la maladie de Chagas chez les femmes enceintes et la transmission verticale de la maladie. MÉTHODES: Des études d\'observation ont été identifiées à partir de huit bases de données électroniques et des détails sur la concept de l\'étude, la population et la prévalence de la maladie de Chagas ont été extraits. Les données ont été regroupées à l\'aide d\'un modèle à effets aléatoires et des cartes choroplèthes ont été créées en fonction des régions et des pays géopolitiques. RÉSULTATS: La recherche a identifié 7.788 articles, dont 50 étaient éligibles. Nous avons observé une prévalence de 9% de la maladie de Chagas chez les femmes enceintes dans les Amériques (intervalle de confiance [IC] à 95%: 8-10, I2 = 99,96%). Une prévalence élevée de la maladie a été identifiée chez les femmes enceintes dans les pays d\'Amérique du Sud (12%, IC95%: 11-13), tandis que des valeurs plus faibles ont été identifiées chez les femmes enceintes d’Amérique du Nord (2%, IC95%: 1-3). Les pays à indice de développement humain (IDH) moyen présentaient une prévalence plus élevée de la maladie de Chagas chez les femmes enceintes (15%, IC95%: 13-16, I2 = 99,98%) que les pays à IDH élevé (3%, IC95%: 2 -3). Le taux de transmission verticale sur le continent était de 2% (IC95%: 1-2). L\'analyse statistique a montré que cette hétérogénéité s\'expliquait par le concept d\'étude, la région des Amériques et le revenu moyen du pays.
Les pays d\'Amérique du Sud et d\'Amérique centrale ont une prévalence élevée et de transmission verticale de la maladie de Chagas. Par conséquent, des dépistages systématiques de cette maladie pendant la période prénatale sont nécessaires en plus du diagnostic et du traitement des enfants à risque d\'infection par Trypanosoma cruzi.

To evaluate co-infection of Strongyloides stercoralis and Trypanosoma cruzi and to assess eosinophilia as a screening test for the detection of S. stercoralis infection in patients with Chagas disease (CD).
A retrospective diagnostic validation study was performed on serum samples from primary care patients diagnosed with CD in the southern Barcelona metropolitan area. All samples with eosinophilia (n = 87) and a random sample of non-eosinophilic sera (n = 180) were selected. Diagnosis of CD was based on positive serology by means of two tests: ORTHO® T. cruzi ELISA test, and BIO-FLASH® Chagas or Bioelisa CHAGAS. SCIMEDX ELISA STRONGY-96 was used to diagnose strongyloidiasis.
Strongyloides stercoralis serology was positive in 15% of patients of whom 95% showed eosinophilia, vs. 21% of those with negative serology (P < 0.001), with differences in the mean eosinophil count (0.49 vs. 0.27 × 109 /l). Only 1.1% of patients with CD but without eosinophilia presented positive serology for S. stercoralis, whereas 44% of patients with CD and eosinophilia did (P < 0.001). Sensitivity and specificity values for eosinophilia were thus 95% and 79%, respectively. PPV was 42.5% and NPV, 98.9%.
The prevalence of co-infection by T. cruzi and S. stercoralis is not negligible and has probably been underestimated for years in many areas, due to frequently subclinical infections. Therefore, serology seems mandatory for these patients and the use of eosinophilia as initial screening could facilitate the task, decreasing the number of analyses to be performed.
Evaluer la coinfection par Strongyloides stercoralis et Trypanosoma cruzi et évaluer éosinophilie comme un test de dépistage pour la détection de l’infection à S. stercoralis chez les patients atteints de la maladie de Chagas (MC). MÉTHODES: Une étude de validation diagnostique rétrospective a été réalisée sur des échantillons de sérum de patients de soins primaires diagnostiqués avec la MC dans la région métropolitaine du sud de Barcelone. Tous les échantillons avec éosinophilie (n = 87) et un échantillon aléatoire de sérums non éosinophiliques (n = 180) ont été sélectionnés. Le diagnostic de la MC était basé sur une sérologie positive au moyen de deux tests: le test ELISA ORTHO® T. cruzi et le test BIO-FLASH® Chagas ou Bioelisa CHAGAS. SCIMEDX ELISA STRONGY-96 a été utilisé pour diagnostiquer la strongyloïdose. RÉSULTATS: La sérologie de S. stercoralis était positive chez 15% des patients dont 95% présentaient une éosinophilie, contre 21% de ceux avec une sérologie négative (P <0,001), avec des différences dans le taux moyen d\'éosinophiles (0,49 contre 0,27 × 109 /L). Seuls 1,1% des patients avec la MC mais sans éosinophilie présentaient une sérologie positive pour S. stercoralis ; contrairement à 44% des patients atteints de la MC avec une éosinophilie (p <0,001). Les valeurs de sensibilité et de spécificité pour l\'éosinophilie étaient ainsi respectivement de 95% et 79%. La VPP était de 42,5% et la VPN, 98,9%.
La prévalence de la coinfection par T. cruzi et S. stercoralis n\'est pas négligeable et a probablement été sous-estimée depuis des années dans de nombreuses régions, en raison d\'infections fréquemment infracliniques. Par conséquent, la sérologie semble obligatoire pour ces patients et l\'utilisation de l\'éosinophilie comme dépistage initial pourrait faciliter la tâche, diminuant le nombre d\'analyses à effectuer.

To evaluate the quality of life (QoL) of patients with Chagas disease (CD) and the association between QoL domains and several clinical, socioeconomic and lifestyle characteristics of this population.
Cross-sectional observational study conducted from March 2014 to March 2017 including a total of 361 outpatients followed at Evandro Chagas National Institute of Infectious Disease, Brazil. QoL was assessed using the Portuguese shorter version of the original WHO Quality of Life questionnaire (WHOQOL-BREF). Information about clinical CD presentation, presence of comorbidities, functional class, previous benznidazole treatment, socioeconomic profile and lifestyle was also obtained.
Environment and physical domains presented the worst QoL scores, while the social relationship domain presented the highest score. Multivariate regression analysis demonstrated that variables independently associated with QoL were functional class, sex, clinical presentation of CD, sleep duration, schooling, physical activity level, smoking, income per capita and residents by domicile.
The low socioeconomic status and the physical limitations imposed by the disease presented an important impact on the QoL reduction among CD patients, especially on environment and physical domains. Strategies to improve QoL among CD patients should be tailored and consider many different variables to maximise improvements not only of patients\' physical but also of their mental health.

Imported Chagas disease (CD) is an emerging health problem in Europe due to immigration from endemic countries. Although WHO currently recommends two different serological methods to establish diagnosis, new tools like the ARCHITECT Chagas assay have potential for use as a single diagnostic test. Our objective was to determine an optimal signal-to-cut-off (S/CO) value for the ARCHITECT Chagas assay to diagnose CD with a single test.
A retrospective study conducted at the 12 de Octubre University Hospital (Madrid, Spain). All patients with requests for Chagas screening between January 2014 and August 2017 were consecutively included. All samples were routinely tested with the ARCHITECT assay. Negative samples (S/CO < 0.8) required no further testing. Immunochromatographic testing (ICT) and/or indirect immunofluorescence (IFI) was used to confirm samples with S/CO ≥ 0.8. Receiver operator characteristic (ROC) curve analysis determined the ARCHITECT S/CO value that yielded 100% specificity and positive predictive value. SPSS software, version 22.0 was used for data analysis.
A total of 4153 samples were analysed; 361 (8.69%) gave a reactive ARCHITECT Chagas result. 261/361 (72.3%) were women; median age was 38 years old (2-79). 92.8% were Bolivian. A total of 307 (85.0%) were confirmed as cases of Chagas; 52 (14.4%) were not infected; two (0.6%) were not evaluable. Seroprevalence was 7.39%. An S/CO ≥ 3.80 yielded 100% specificity (95% confidence interval [CI], 0.93-1.00) and 100% positive predictive value (95% CI, 0.99-1.00).
Using S/CO ≥ 3.80, the ARCHITECT Chagas could be used as a single test for diagnosis of chronic CD in Bolivian immigrants. Patients with S/CO between 0.80 and 3.80 would require additional testing.

To develop an alcohol-free solution suitable for children of benznidazole, the drug of choice for treatment of Chagas disease.
In a quality-by-design approach, a systematic optimisation procedure was carried out to estimate the values of the factors leading to the maximum drug concentration. The formulations were analysed in terms of chemical and physical stability and drug content. The final preparation was subjected to an in vivo palatability assay. Mice were infected and treated orally in a murine model.
The results showed that benznidazole solubility increased up to 18.38 mg/ml in the optimised co-solvent system. The final formulation remained stable at all three temperatures tested, with suitable drug content and no significant variability. Palatability of the preparation was improved by taste masking of BZL. In vivo studies showed that both parasitaemia and mortality diminished, particularly at a dose of 40 mg/kg/day.
Quality by design was a suitable approach to formulate a co-solvent system of benznidazole. The in vivo studies confirmed the suitability of the optimised such solutions to diminish both parasitaemia and mortality. Thus, this novel alternative should be taken into account for further clinical evaluation in all age ranges.

In a previous study performed by our group, Strongyloides stercoralis infection in patients with Chagas disease was associated with higher proportion of Trypanosoma cruzi DNA detection in peripheral blood. The aim of the study was to confirm this association in a larger cohort of patients.
Cross-sectional study of all patients with Chagas disease diagnosed from 2005 to 2015 during blood donation at the Catalan Blood Bank. Demographic data and T. cruzi RT-PCR were collected. S. stercoralis infection diagnosis was based on a serological test.
Two hundred and two blood donors were included. T. cruzi RT-PCR was positive in 72 (35.6%) patients, and S. stercoralis serology was positive in 22 (10.9%) patients. Patients with positive S. stercoralis serology had higher proportion of positive T. cruzi RT-PCR than those with negative serology (54.5% vs. 33.3%, P = 0.050), and the difference increased when taking a serological index cut-off of 2.5, which increases the specificity of the test to detect a confirmed strongyloidiasis (60% vs. 33%, P = 0.017).
Patients with Chagas disease with positive S. stercoralis serology had higher proportion of positive T. cruzi RT-PCR in peripheral blood than those with negative serology, which reflects the potential immunomodulatory effects of S. stercoralis in T. cruzi co-infected patients.

To evaluate the correlation of the total distance walked during the six-minute walk test (6MWT) with left ventricular function and quality of life in patients with Chagas Disease (ChD) complicated by heart failure.
This is a cross-sectional study of adult patients with ChD and heart failure diagnosed based on Framingham criteria. 6MWT was performed following international guidelines. New York Heart Association functional class, brain natriuretic peptide (BNP) serum levels, echocardiographic parameters and quality of life (SF-36 and MLHFQ questionnaires) were determined and their correlation with the distance covered at the 6MWT was tested.
Forty adult patients (19 male; 60 ± 12 years old) with ChD and heart failure were included in this study. The mean left ventricular ejection fraction was 35 ± 12%. Only two patients (5%) ceased walking before 6 min had elapsed. There were no cardiac events during the test. The average distance covered was 337 ± 105 metres. The distance covered presented a negative correlation with BNP (r = -0.37; P = 0.02), MLHFQ quality-of-life score (r = -0.54; P = 0.002), pulmonary artery systolic pressure (r = -0.42; P = 0.02) and the degree of diastolic dysfunction (r = -0.36; P = 0.03) and mitral regurgitation (r = -0.53; P = 0.0006) and positive correlation with several domains of the SF-36 questionnaire.
The distance walked during the 6MWT correlates with BNP, quality of life and parameters of left ventricular diastolic function in ChD patients with heart failure. We propose this test to be adopted in endemic areas with limited resources to aid in the identification of patients who need referral for tertiary centres for further evaluation and treatment.