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Transplacental transmission by Trypanosoma cruzi (T. cruzi) infection can be effectively treated if parasiticide drugs are administered as early as possible during childhood. Furthermore, an ideal situation would be to diagnose the infection near birth in order to avoid the loss of patients during the subsequent follow-up. These situation are desirable due to the maximum benefit of drugs in early stages which, consequently, implies a relevant contribution to eliminate mother-to-child transmission. However, available techniques for that purpose have limitations as being operator-dependent (microhematocrit), require several months follow-up (IgG detection) or specialized laboratories (PCR). In this study we propose to detect specific IgM antibodies (Ab) by developing a capture-based ELISA employing an improved antigen (Ag) to diagnose the transplacental transmission of T. cruzi, and in consequence, to enhance access to effective treatment. Firstly, a new chimera Ag (CP4) was obtained from the fusion of CP1 and CP3 protein, carrying FRA, SAPA, MAP, TSSAII/V/VI and TcD Ag from T. cruzi. Then, we optimized the assay by capturing IgM Ab with a polyclonal anti-IgM Ab and evaluating three Ag formulations to detect specific IgM bound. The formulations were formed as follows: i) F1: CP1 and CP3; ii) F2: CP1, CP3, B13 and P2β; iii) F3: by CP4. Detection of Ab-binding Ag was carried out using an anti-His Ab since all Ag were expressed with a His-tag. The evaluation panel consisted of sera from vertically infected children under 1-year-old (6 younger than 15 days, 7 older) and samples from non-infected children of women with chronic Chagas Disease. The ELISA assay employing CP4 showed better performance with notable high sensitivity and specificity (92.3% and 93.9%, respectively). Positive and negative likelihood ratios of the test (15.2 and 0.082) suggest its potential clinical relevance in term of post-test probability of infection. In conclution, we developed a standardized and non-operator dependent test to detect specific anti-T. cruzi IgM Ab. Although increased sample size is needed for its validation, our results indicate that this capture-based technique employing CP4 Ag can certainly improve the diagnosis of connatal infection., (Copyright © 2020. Published by Elsevier B.V.)

Since the immune response mounted by the host to a particular microorganism might be influenced by the acquired immunological experience due to previous contact with other microorganisms, we performed a cross-sectional study to explore the pattern of Trypanosoma cruzi infection-related antibodies in T. cruzi-seropositive individuals presenting concomitant tuberculosis, or the antecedent of BCG vaccination. Sampled individuals were grouped as follows: patients with Chagas disease, not vaccinated with BCG, who further developed pulmonary tuberculosis; individuals with Chagas disease, BCG-vaccinated; and subjects with Chagas disease, presenting neither BCG scar nor tuberculosis disease. Non-vaccinated individuals or without tuberculosis, presented the highest values of anti-PH (P < 0.001), anti-FRA (P < 0.001), anti-p2β (P = 0.0023) and anti-B13 (P < 0.001) antibodies. The present findings constitute the first demonstration of the potential influence of concomitant tuberculosis on Chagas disease., (© FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective The aim of the present research was to evaluate the correlation of vertically transmitted IgG antibodies induced by T. cruzi and newborn early outcome assessment, mainly birth weight and gestational age. Methods We performed a cross-sectional study with 183 pregnant women (64 with asymptomatic Chagas disease) and their newborns. Both were subjected to complete clinical examination. Peripheral parasitemia was assessed in mother and neonates by parasite detection through microscopic examination of the buffycoat from mother's peripheral and cord blood. Antibodies induced by T. cruzi, such as anti-FRA, anti-B13, anti-p2β and anti-T. cruzi were assessed by immunoassay. Birth weight, general condition evaluation by APGAR Score and gestational age by Capurro Score, were determined in newborns. Results The rate of stillbirth background and pregnancy-induced hypertension were higher in patients with Chagas disease (p = 0.01 and p = 0.02, respectively). Parasitemia was detectable in 17 mothers and 4 newborns. The newborns of mothers with detectable parasitemia presented decreased gestational age (p = 0.006) and body weight (p = 0.04). Mostly all the mothers with Chagas disease and all their newborns have positive values of antibodies induced by T. cruzi; however, only anti-p2β showed to be related to the presence of complication during pregnancy (OR 2.35, p = 0.036), and to low birth weight (OR 1.55, p = 0.02). Conclusions Low birth weight and decreased postnatal estimation of maturity were related to detectable parasitemia in the mother. Also, vertical transmission of T. cruzi-induced autoantibodies might have clinical implication in newborns given the negative association between anti-p2β values and weight.

Studies indicate that Trypanosoma cruzi is capable of inducing immunological disturbances such as decreased expression of molecules involved in T-cell survival and costimulation for antigen-driven T-cell responses. On the other hand, several reports have described that BCG vaccination induces a T-helper 1-type immune response with protective effects in different pathologies. In this regard, we evaluated whether BCG vaccination coexists with a better clinical and immunological profile of chronic Chagas heart disease (CCHD). We performed a cross-sectional study in T. cruzi seropositive patients categorized according the BCG vaccine background and to the well-established CCHD classification provided by Storino et al. All individuals were subjected to a complete clinical examination. All patients presented detectable levels of autoantibodies anti-p2β, anti-B13, anti-FRA and antiparasite homogenate immunoglobulins, which were unrelated to age and sex distribution or blood pressure values. Comparisons according to BCG vaccination revealed that individuals who had not been vaccinated presented higher values of antibodies, and patients without BCG vaccine had an OR of 6.1 (95 % CI 1.23-29.25, p = 0.02) for globally dilated cardiomyopathy with reduced ejection fraction (Hosmer and Lemeshow test of 5.2 p = 0.73). Our results suggest that BCG vaccination coexists with a better clinical and immunological profile of CCHD, associated with lower cardiac involvement.

Background: Studies indicate that antibodies cross-reacting with cardiac β1 adrenergic receptors are likely to play a role in the development of chronic Chagas heart disease (CCHD). In parallel, clinical trials have shown that β1 antagonist drugs exert beneficial effects in the prognosis of patients with CCHD. In a group of patients with CCHD undergoing therapy with β1-blockers, we have now evaluated the levels of anti-p2β antibodies and the severity of CCHD., Methods: We performed a cross-sectional study in Trypanosoma cruzi seropositive patients categorized according to a standard CCHD classification. All individuals were subjected to a complete clinical examination., Results: There was no association between CCHD stages, electrocardiographic conduction disturbances, and echocardiogram pathological signs with the levels of autoantibodies. However, when patients were analyzed according to selective cardio-β1-blocker therapy, those receiving treatment had higher levels of anti-p2β. Patients from CCHD stage III treated with combined therapy of cardio-β1-selective blockers, enalapril, and statins, presented decreased cardiac involvement and lower score of risk of mortality than individuals from the same group who were not treated., Conclusions: Our results suggest that selective cardio-β1-blockers might modify the autoantibody anti-p2β levels, and that combined therapy in patients with stage III CCHD might be associated with lower cardiac involvement and risk score of mortality in patients with heart failure. Longitudinal studies will help to ascertain the proper role of β1-blockers in the immunopathological processes underlying chronic Chagas disease., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)