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Background and Aims: Chagas disease is a common cause of heart failure (HF) and death in developing countries. Although stroke is known to occur in these patients, an accurate estimate of stroke incidence is lacking. We aimed to determine the incidence of stroke and death in patients with HF, comparing Chagas and non-Chagas etiologies., Methods: Cohort of stroke-free patients with HF (Framingham criteria) followed in a university-based outpatient clinic in Brazil. Baseline characteristics included sociodemographic, risk factor assessment, echocardiographic and electrocardiographic findings. Chagas disease was defined by appropriate serologic tests. Cause-specific Cox regression was used to search for predictors of stroke or death as separate outcomes., Results: We studied 565 patients with HF between January 2003 and December 2018, mean age 54.3 ± 12.9 years, 305 (54.0%) females, 271/535 (50.7%) with Chagas disease. Chagas patients were older (55.5 vs. 53.1 years), more frequently women (60.5% vs. 47.3%), less frequently harbored coronary artery disease (14.5% vs. 34.1%) when compared to non-Chagas patients. Echocardiography showed more severe disease among non-Chagas patients [median left ventricle ejection fraction (LVEF) 37.3% vs. 47.0%]. Over a mean 42.9 (±34.4) months, we followed 404 (71.5%) patients, completing 1442 patient-years of follow-up. Stroke incidence was higher in Chagas when compared to non-Chagas patients (20.2 vs. 13.9 events per 1000 patient-years), while death rate was similar (41.6 vs. 43.1 deaths per 1000 patient-years). In the multivariable analysis for stroke outcome adjusted for LVEF and arrhythmias, cause-specific hazard ratio (CSHR) for Chagas was 2.54 (95% confidence interval 1.01-6.42, p  = 0.048). Chagas disease was also associated with increased risk of death (CSHR 1.83; 95% confidence interval 1.04-3.24, p  = 0.037)., Conclusion: Chagas disease is associated with increased risk of stroke and death when compared to other etiologies of HF, independently of HF severity or cardiac arrhythmias, suggesting other factors contribute to increased stroke risk and mortality in Chagas disease. Early prevention and treatment of Chagas disease is imperative to reduce a later risk of stroke in endemic areas.

Objective: To determine the course of serological tests in subjects with chronic Trypanosoma cruzi infection treated with anti-trypanosomal drugs., Methods: A systematic review and meta-analysis was conducted using individual participant data. Survival analysis and the Cox proportional hazards regression model with random effects to adjust for covariates were applied. The protocol was registered in the PROSPERO database (http://www.crd.york.ac.uk/PROSPERO; CRD42012002162)., Results: A total of 27 studies (1296 subjects) conducted in eight countries were included. The risk of bias was low for all domains in 17 studies (63.0%). Nine hundred and thirteen subjects were assessed (149 seroreversion events, 83.7% censored data) for enzyme-linked immunosorbent assay (ELISA), 670 subjects (134 events, 80.0% censored) for indirect immunofluorescence assay (IIF), and 548 subjects (99 events, 82.0% censored) for indirect hemagglutination assay (IHA). A higher probability of seroreversion was observed within a shorter time span in subjects aged 1-19 years compared to adults. The chance of seroreversion also varied according to the country where the infection might have been acquired. For instance, the pooled adjusted hazard ratio between children/adolescents and adults for the IIF test was 1.54 (95% confidence interval 0.64-3.71) for certain countries of South America (Argentina, Bolivia, Chile, and Paraguay) and 9.37 (95% confidence interval 3.44-25.50) for Brazil., Conclusions: The disappearance of anti-T. cruzi antibodies was demonstrated along the course of follow-up. An interaction between age at treatment and country setting was found., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Data from a six-year follow-up of Trypanosoma cruzi-infected adolescents enrolled in a randomized, double-blind, clinical trial of benznidazole showed successful chemotherapy in 64.7% (95% confidence interval [CI] = 50.2-78.7) and 84.7% (95% CI = 66.8-92.9), respectively, by intention-to treat and by per protocol analysis measured by seronegativity in a chemiluminescent enzyme-linked immunosorbent assay with a purified trypomastigote mucin antigen. No incident case of cardiomyopathy was detected by electrocardiogram assessment in this cohort of adolescents who had been infected in childhood. The persistent and consistently long-term negative serologic reactions suggest the absence of the parasite in the treated patients and reinforces the recommendation of early benznidazole chemotherapy for T. cruzi-infected infants as a public health policy in endemic areas.

Assessment of cure of Trypanosoma cruzi infection by antibody seroconversion usually involves several years of follow-up. Parasitological negativity is useless for cure assessment, since even untreated patients mostly show negative results; conversely, positive tests are of great value because they indicate treatment failure. Here, PCR was used to assess the rate of specific chemotherapy failure in a well-characterized Brazilian cohort of T. cruzi-seropositive children, who were enrolled in a field trial of benznidazole (Bz) efficacy. Paired blood samples from 111 children were taken at baseline and 36 months after treatment with either Bz (n = 58) or a placebo (n = 53). DNA extraction and PCR amplification were carried out as previously described, and hybridization was performed with all PCR products. At the end of follow-up, PCR was positive for 39.6% of the patients in the Bz group versus 64.2% in the placebo group (P = 0.01). Untreated patients had a 1.6-fold-higher chance of remaining positive by PCR than those in the Bz group (P < 0.05). We conclude that PCR is a useful tool for revealing therapeutic failure of T. cruzi infection on a short-term basis.

As part of a major epidemiologic study on Chagas' disease, we compared the prevalence of electrocardiographic (ECG) abnormalities among 141 school children 7-12 years of age and seropositive for Trypanosoma cruzi, and 282 age-, sex-, and school-matched seronegative children in an endemic area in Brazil. The prevalence of ECG abnormalities was 11.3% among seropositive children and 3.5% among seronegative children (odds ratio = 3.5, 95% confidence interval [CI] = 1.5-8.4). The prevalence rate of ECG alterations was 10.7% for seropositive males versus 8.9% for seropositive females. Complete right bundle branch block (CRBBB), which is highly suggestive of Chagas' disease cardiopathy, was diagnosed in nine (6.4%) seropositive children and in only one (0.3%) seronegative child (odds ratio = 18.5, 95% CI = 2.3-146.5, attributable fraction = 58.3%). Five incident new cases of CRBBB were diagnosed after a 36-month follow-up of seropositive children who were enrolled in an independent clinical field trial. No case of frequent and/or multifocal ventricular premature beats was found in the cohort of children. The surprisingly high frequency of early ECG abnormalities, which indicates a rapid evolution from infection to disease, suggests the existence of endemic areas with a particular accelerated disease progression that was not described before. Under such conditions, a public health chemotherapy program focusing on the treatment of young seropositive children would be recommended.

Ten Trypanosoma cruzi stocks recently isolated from patients in acute and chronic phases of Chagas disease were inoculated to susceptible (A/Sn) mice. The mice were inoculated with 10(4) trypomastigotes intraperitoneally and monitored for parasitaemia and mortality for up to 300 d. The results demonstrated that (i) T. cruzi stocks isolated from patients in the acute phase killed animals, while stocks from patients in the chronic phase did not; (ii) survival curves differed statistically among mice infected with lethal stocks, and (iii) parasite burden did not affect the mortality rate of mice.

Background: Benznidazole, a nitroimidazole derivative, has been recommended for the treatment of acute and congenital Trypanosoma cruzi infection (Chagas' disease). We have examined the safety and efficacy of this drug in the treatment of the early chronic phase of T cruzi infection., Methods: Between 1991 and 1995, we carried out a randomised, double-blind, placebo-controlled trial in a rural area of Brazil with endemic Chagas' disease. 82% of 2434 schoolchildren (aged 7-12 years) identified in a census were screened for antibodies to T cruzi by indirect immunofluorescence, indirect haemagglutination, and ELISA. 130 were positive in all tests and were randomly assigned benznidazole (7.5 mg/kg daily for 60 days by mouth) or placebo. The primary endpoint for efficacy was the disappearance of specific antibodies (negative seroconversion) by the end of 3-year follow-up. The secondary endpoint was the reduction of antibody titres on repeated serological tests. One child moved away from the area just after randomisation and was excluded from the analyses. Insecticidal measures were taken throughout the trial to reduce the risk of reinfection., Findings: Minor side-effects requiring no specific medication were recorded in a small proportion of individuals. On a chemiluminescent ELISA with purified trypomastigote glycoconjugate, serum from all participants was positive at the beginning of the trial. At the end of follow-up, 37 (58%) of the 64 benznidazole-treated participants and 3 (5%) of those who received placebo were negative for T cruzi antibodies. The efficacy of benznidazole treatment estimated by intention to treat was 55.8% (95% CI 40.8-67.0). At the end of follow-up, children who received benznidazole had five-fold lower geometric mean titres by indirect immunofluorescence than placebo-treated children (196[147-256] vs 1068[809-1408], p < 0.00001)., Interpretation: The trial showed that a 60-day course of benznidazole treatment of early chronic T cruzi infection was safe and 55.8% effective in producing negative seroconversion of specific antibodies. The results are very encouraging and justify the recommendation of treatment for seropositive children as public health policy.

An active entomologic survey was conducted by a team of trained health workers in a rural area endemic for Chagas' disease in central Brazil. They used pyrethrum as a flushing agent and 4,232 houses were inspected for triatomine bugs both inside and in the immediate environs. Houses with Triatoma infestans or evidence of an established colony were identified and defined as infested houses (cases). The building and environmental characteristics of 161 randomly selected infested houses were compared with 161 matched, noninfested houses (controls) that were the shortest distance from the infested house. Domestic and peridomestic potential risk factors associated with house infestation by Triatoma infestans were assessed by logistic regression analysis. Incomplete house construction (odds ratio [OR] = 2.5, 95% confidence interval [CI] = 1.5-4.1) was confirmed as a risk factor related to the presence or evidence of Triatoma infestans in the dwellings. The study also disclosed a statistically significant association between the presence of rats (OR = 1.6, 95% CI = 1.1-2.6) and indoor crop storage (OR = 2.3, 95% CI = 1.1-5.2) and house infestation. Further experimental field studies using tagged rodents should be conducted to assess their epidemiologic role in the domestic chain of Trypanosoma cruzi transmission.

This population-based case-control study was conducted in northern Goias State, central Brazil, in rural settings under vector control surveillance. One hundred forty-nine children seropositive for Trypanosoma cruzi antibodies, selected in a cross-sectional survey carried out in village schools, were compared with 298 seronegative classmate controls matched for age, sex, and place of residence. Information on potential environmental, familiar, and social economic risk factors for T. cruzi infection was collected during household visits, and interviews with parents and entomologic inspections of domestic and peridomestic environments were conducted. The presence of triatomines in dwellings or evidence of triatomine colonization was found to be statistically associated with seropositivity in children. The presence of exuviae and a report of triatomines indoors or outdoors by householders in the past were strong predictors of an infected child. Children from seropositive mothers had a 3.9-fold increase in the risk of having anti-T. cruzi antibodies after adjusting for the confounding variables, including triatomine capture, mother's age, and family size in multivariate analysis. Parent's report of vector presence showed a 97.7% sensitivity in identifying a dwelling with at least one seropositive child. The possibility of transplacental T. cruzi transmission and its implication for Chagas' disease control were considered.

Characteristics and possible risk factors associated with Trypanosoma cruzi infection among blood donors were assessed within a routine screening programme in blood banks in an endemic area of Chagas disease. 6,172 voluntary blood donors were interviewed and tested for anti-T. cruzi antibodies by Haemagglutination and Complement Fixation tests in six blood banks in Goiânia-Central Brazil from October 1988 to April 1989. An overall prevalence of 2.3% for T. cruzi infection was obtained, being 3.3% for first-time blood donors and 1.9% for regular ones (p < 0.01). Considering this seropositivity among regular blood donors, selection of candidates relying only on the history of previous donation was found to be inadequate. The risk of infection increased inversely with the degrees of education and monthly income. There was a 9.2 risk of infection (95% CI 3.8-22.6) for those who had lived more than 21 years in an endemic area compared to subjects who had never lived in rural settings, after multivariate analysis. These informations may help to review the criteria of selection of donors in order to improve quality of blood products in endemic areas.

The present study compares the results of serological screening for Trypanosoma cruzi infection done at blood banks with results obtained in Chagas' disease studies undertaken by the Reference Laboratory of the Federal University of Goiás (UFG) and evaluates the use of the enzyme-linked immunosorbent assay (ELISA) for this purpose. The study was conducted with data from six of the eight blood banks in the city of Goiânia in central Brazil, an urban area in which this infection is highly endemic. The population studied consisted of 1,513 volunteers who had donated blood for the first time between October 1988 and April 1989. The sample represented 50% of all first-time blood donors during the period. Of these donors, 94% were residents of urban areas, and of these, approximately 26% had migrated from the countryside. Nearly 90% of the blood donations in the city are received at these banks, which normally use the indirect hemagglutination and complement-fixation tests. The samples selected for the study of T. cruzi antibody in first-time blood donors were assayed at the Reference Laboratory of the Federal University of Goiás using the indirect hemagglutination (IH), indirect immunofluorescence (IF), and enzyme-linked immunosorbent assay (ELISA) tests, independently of the serological classification performed by the blood banks. Comparison of the results provided by the latter with the positivity pattern established in the study (IH and IF yielded simultaneous positive results in the Reference Laboratory) revealed a relative sensitivity of 77%, with extremes ranging between 50% and 100%, depending on the blood bank studied.(ABSTRACT TRUNCATED AT 250 WORDS)

The study reported here compares results obtained by blood banks screening sera for chagasic (Trypanosoma cruzi) infection with results obtained by the Chagas' Disease Reference Laboratory of the Federal University of Goiás in Goiânia, Brazil. It also evaluates results obtained using the ELISA technique to screen the study sera. The survey used data from six of eight blood banks serving the city of Goiânia, an urban region of Central Brazil where Chagas' disease is highly endemic. The survey population consisted of 1,513 voluntary first-time blood donors whose donations occurred between October 1988 and April 1989. This group included 50% of all the first-time blood donors in that period. The six participating blood banks, which accounted for about 90% of all blood donations in Goiânia during the study period, routinely used indirect hemagglutination (IHA) and complement fixation (CF) tests to screen sera for antibodies to T. cruzi. Comparison of the results provided by the blood banks with the reference laboratory's results indicated a relative sensitivity of 77%, which ranged from 50% to 100% depending on the blood bank studied. The comparison, which found 12 false negative results, indicated that transfusions of infected blood might have occurred despite the serologic screening performed by the blood banks. Relative to the standard of positivity established for the study, the enzyme-linked immunosorbent assay (ELISA) technique was found to have a sensitivity of 96.3%. Considering as positive only those sera yielding positive IHA and indirect immunofluorescence (IIF) test results, the ELISA technique yielded 2 false negative and 41 false positive responses.(ABSTRACT TRUNCATED AT 250 WORDS)

The seroprevalence of Trypanosoma cruzi infection among children is a sensitive indicator for assessing the effectiveness of programmes for control of Chagas disease. In this study we report the result of a cross-sectional serological survey carried out among schoolchildren living in a poor rural area in central Brazil. Eluates of blood collected on filter-paper were tested for anti-T. cruzi antibodies using immunofluorescence, haemagglutination, and enzyme-linked immunosorbent assays. The overall seroprevalence of T. cruzi infection was 7.9%, which compared with the findings of the national survey carried out in 1975-80 indicates that a twofold-to-threefold reduction in prevalence has occurred over the last 10 years. This is consistent with a reduction of transmission in the area, probably related to vector control efforts. Based on our results, the incidence of new cases was estimated to be 44 per annum in the study region. In rural areas with a scattered population, surveillance of T. cruzi transmission by serological screening of children at school entry is more practical and economical than entomological evaluation for assessing both the risk of transmission in the community and the efficacy of vector control measures. A sample size of around 1000 schoolchildren is sufficient to detect prevalences as low as 2%, and such an approach would be practical and applicable to most areas where Chagas disease is endemic.

Between October 1988 and April 1989 a cross-sectional survey was carried out in six out of eight blood banks of Goiánia, Central Brazil. Subjects attending for first-time blood donation in the mornings of the study period (n = 1358) were interviewed and screened for T. cruzi infection as a part of a major study among blood donors. Tests to anti-T. cruzi antibodies were performed, simultaneously, by indirect hemagglutination test (IHA) and complement fixation test (CFT). A subject was considered seropositive when any one of the two tests showed a positive result. Information on age, sex, place of birth, migration and socio-economic level was recorded. Results from this survey were compared with seroprevalence rates obtained in previous studies in an attempt to analyse trend of T. cruzi infection in an endemic urban area. The overall seroprevalence of T. cruzi infection among first-time donors was found to be 3.5% (95% confidence interval 2.5%-4.5%). The seroprevalence rate increased with age up to 45 years and then decreased. Migrants from rural areas had higher seroprevalence rates than subjects from urban counties (1.8%-16.2% vs. 0%-3.6%). A four fold decrease in prevalence rates was observed when these rates were compared with those of fifteen years ago. Two possible hypotheses to explain this difference were suggested: 1. a cohort effect related with the decrease of transmission in rural areas and/or 2. a differential proportion of people of rural origin among blood donors between the two periods. The potential usefulness of blood banks as a source of epidemiological information to monitor trends of T. cruzi infection in an urban adult population was stressed.