Dissecting slander and crying for justice: Carlos Chagas and the Nobel Prize of 1921

Chagas disease was discovered by Carlos Chagas in 1909. Chagas worked at Oswaldo Cruz Institute, where the bases of experimental medicine were settled in Brazil, and that had no connection with the Faculty of Medicine of Rio de Janeiro. Chagas had several enemies at Oswaldo Cruz Institute mainly because of his election to Head of Service in 1910, and for the position of Oswaldo Cruz Directorship in 1917. Furthermore, Chagas gained enemies at Faculty of Medicine of Rio de Janeiro, which did not like to see the economical political autonomy of Oswaldo Cruz Institute. This allowed the Institute not only to perform top experimental research, but also to take the leadership of research in the country.     

Precordial chest pain in patients with chronic Chagas disease

Precordial chest pain affects about 15% to 33% of patients with chronic Chagas disease. In the absence of megaesophagus, it should be ascribed to chronic Chagas heart disease. Precordial chest pain is atypical because it can usually neither be associated to physical exercise nor be alleviated by nitroglycerin. However, in certain circumstances, precordial chest pain can masquerade as acute coronary syndrome. Although obstructive coronary artery disease can occasionally be found, microvascular angina seems to be the mechanism behind such phenomenon. Precordial chest pain not always has a benign clinical course; sometimes, it can herald a dismal prognosis. On the basis of cases previously reported, it seems that nitrates, betablockers and/or calcium channel blockers can be of value in the treatment of this condition.     

ECG Manifestations of the Biggest Outbreak of Chagas Disease due to Oral Infection in Latin-America

Background

Chagas disease affects more than 15 million people worldwide. Although vector-borne transmission has decreased, oral transmission has become important. Recently, our group published the clinical and epidemiological characteristics of the largest outbreak of orally transmitted Chagas disease reported till date. Objective: To describe electrocardiographic changes occurring in the study population during the outbreak caused by ingestion of contaminated guava juice.

Methods

We evaluated 103 positive cases, of which 76 (74%) were aged ≤ 18 years (average age: 9.1 ± 3.1 years) and 27 (26%) were aged > 18 years (average age: 46 ± 11.8 years). All patients underwent clinical evaluations and ECG. If the patients had palpitations or evident alterations of rhythm at baseline, ambulatory ECG monitoring was performed.

Results

A total of 68 cases (66%; 53 children and 15 adults) had ECG abnormalities. Further, 69.7% (53/76) of those aged ≤ 18 years and 56% (15/27) of those aged >18 years showed some ECG alteration (p = ns). ST-T abnormalities were observed in 37.86% cases (39/103) and arrhythmias were evident in 28.16% cases (29/103). ST alterations occurred in 72% of those aged ≤18 years compared with 19% of th ose aged >18 years (p < 0.0001).

Conclusion

This study reports the largest number of cases in the same outbreak of acute Chagas disease caused by oral contamination, with recorded ECGs. ECG changes suggestive of acute myocarditis and arrhythmias were the most frequent abnormalities found.     

Prevalence of Trypanosoma cruzi/HIV coinfection in southern Brazil

Chagas disease reactivation has been a defining condition for acquired immune deficiency syndrome in Brazil for individuals coinfected with Trypanosoma cruzi and HIV since 2004. Although the first coinfection case was reported in the 1980s, its prevalence has not been firmly established. In order to know coinfection prevalence, a cross-sectional study of 200 HIV patients was performed between January and July 2013 in the city of Pelotas, in southern Rio Grande do Sul, an endemic area for Chagas disease. Ten subjects were found positive for T. cruzi infection by chemiluminescence microparticle immunoassay and indirect immunofluorescence. The survey showed 5% coinfection prevalence among HIV patients (95% CI: 2.0–8.0), which was 3.8 times as high as that estimated by the Ministry of Health of Brazil. Six individuals had a viral load higher than 100,000 copies per μL, a statistically significant difference for T. cruzi presence. These findings highlight the importance of screening HIV patients from Chagas disease endemic areas.     

Western blotting method (TESAcruzi) as a supplemental test for confirming the presence of anti-Trypanosoma cruzi antibodies in finger prick blood samples from children aged 0–5 years in Brazil

Some Latin American countries have plans for total control and/or eradication of Chagas disease by the main vector (Triatoma infestans) and by blood transfusion. To achieve this, patients with Chagas disease must be identified. A Western blotting test, TESAcruzi, is described as a supplemental test for diagnosis of Chagas disease using samples collected from children <5 years living in different states of Brazil. Blood samples collected by finger prick on filter paper were sent to the test laboratory by a central laboratory to confirm results obtained previously. Ten percent of negative samples, all doubtful and all positive samples were received. Commercial reagents, IgG indirect immunofluorescence, enzyme immunoassay, and a recently introduced TESAcruzi test were used. From 8788 samples, 163 (1.85%) were reactive by IgG-ELISA and 312 (3.55%) by IgG IIF. From these, 77 (0.87%) were reactive in the TESAcruzi test. The results had high clinical value to identify those truly infected.     

Assessment of Galectin-3 Polymorphism in Subjects with Chronic Chagas Disease

Background

Galectin-3, a β-galactoside binding lectin, has been described as a mediator of cardiac fibrosis in experimental studies and as a risk factor associated with cardiovascular events in subjects with heart failure. Previous studies have evaluated the genetic susceptibility to Chagas disease in humans, including the polymorphisms of cytokine genes, demonstrating correlations between the genetic polymorphism and cardiomyopathy development in the chronic phase. However, the relationship between the galectin-3 single nucleotide polymorphism (SNP) and phenotypic variations in Chagas disease has not been evaluated.

Objective

The present study aimed to determine whether genetic polymorphisms of galectin-3 may predispose to the development of cardiac forms of Chagas disease.

Methods

Fifty-five subjects with Chagas disease were enrolled in this observational study. Real-time polymerase chain reaction (PCR) was used for genotyping the variants rs4644 and rs4652 of the galectin-3 gene.

Results

For the SNP rs4644, the relative risk for the cardiac form was not associated with the genotypes AA (OR = 0.79, p = 0.759), AC (OR = 4.38, p = 0.058), or CC (OR = 0.39, p = 0.127). Similarly, for the SNP rs4652, no association was found between the genotypes AA (OR = 0.64, p = 0.571), AC (OR = 2.85, p = 0.105), or CC (OR = 0.49, p = 0.227) and the cardiac form of the disease.

Conclusion

Our results showed no association between the different genotypes for both SNPs of the galectin-3 gene and the cardiac form of Chagas disease.     

The efficacy of photochemical treatment with methylene blue and light for the reduction of Trypanosoma cruzi in infected plasma

Background and Objectives  Chagas disease is a transfusion-transmitted infection. This study evaluates the efficacy of a methylene blue (MB) and light system for reducing the viability of Trypanosoma cruzi in plasma.
Materials and Methods  Trypanosoma cruzi strains were spiked in plasma pools. Treatment arms included combined filtration, MB, light and freezing. Post-treatment parasite viability was assayed through in vitro cultures and in vivo inoculation in inducible nitric oxide synthase- and interferon-γ-receptor-deficient mice.
Results  The filtration, MB and light combined treatment showed a log reduction of > 3·4 in in vitro cultures, and log reductions that ranged from > 4·9 to > 5·8 in deficient mice inoculated with different T. cruzi strains.
Conclusion  The treatment of plasma units with the MB and light system reduces the T. cruzi burden and could be useful in preventing transfusion-transmitted Chagas disease.     

Echocardiographic Parameters and Survival in Chagas Heart Disease with Severe Systolic Dysfunction

Background

Echocardiography provides important information on the cardiac evaluation of patients with heart failure. The identification of echocardiographic parameters in severe Chagas heart disease would help implement treatment and assess prognosis.

Objective

To correlate echocardiographic parameters with the endpoint cardiovascular mortality in patients with ejection fraction < 35%.

Methods

Study with retrospective analysis of pre-specified echocardiographic parameters prospectively collected from 60 patients included in the Multicenter Randomized Trial of Cell Therapy in Patients with Heart Diseases (Estudo Multicêntrico Randomizado de Terapia Celular em Cardiopatias) - Chagas heart disease arm. The following parameters were collected: left ventricular systolic and diastolic diameters and volumes; ejection fraction; left atrial diameter; left atrial volume; indexed left atrial volume; systolic pulmonary artery pressure; integral of the aortic flow velocity; myocardial performance index; rate of increase of left ventricular pressure; isovolumic relaxation time; E, A, Em, Am and Sm wave velocities; E wave deceleration time; E/A and E/Em ratios; and mitral regurgitation.

Results

In the mean 24.18-month follow-up, 27 patients died. The mean ejection fraction was 26.6 ± 5.34%. In the multivariate analysis, the parameters ejection fraction (HR = 1.114; p = 0.3704), indexed left atrial volume (HR = 1.033; p < 0.0001) and E/Em ratio (HR = 0.95; p = 0.1261) were excluded. The indexed left atrial volume was an independent predictor in relation to the endpoint, and values > 70.71 mL/m² were associated with a significant increase in mortality (log rank p < 0.0001).

Conclusion

The indexed left atrial volume was the only independent predictor of mortality in this population of Chagasic patients with severe systolic dysfunction.     

Chagas Cardiomyopathy is Associated With Higher Incidence of Stroke: A Meta-analysis of Observational Studies

BackgroundChagas disease (CD) has been associated with an elevated risk of stroke, but current data are conflicting and prospective controlled studies are lacking. We performed a systematic review and meta-analysis examining the association between stroke and CD.MethodsPubmed, Embase, Cochrane Central, Latin American database, and unpublished data were searched with the use of the following terms: (“Chagas” OR “American trypanosomiasis”) AND (“dilated” OR “ischemic” OR “idiopathic” OR “nonChagasic” OR “stroke” OR “cerebrovascular”). We included studies that reported prevalence or incidence of stroke in a CD group compared with a non-CD control group. Odds ratios (ORs) and their 95% confidence intervals (CIs) were computed with the use of a random-effects model.ResultsA total of 8 studies and 4,158 patients were included, of whom 1,528 (36.7%) had CD. Risk of stroke was elevated in the group of patients with CD (OR 2.10, 95% CI 1.17–3.78). Similar results were observed in a subanalysis of cardiomyopathy patients (OR 1.74, 95% CI 1.02–3.00) and in sensitivity analysis with removal of each individual study. Furthermore, exclusion of studies at higher risk for bias also yielded consistent results (OR 1.70, 95% CI 1.06–2.71). Subanalysis restricted to studies that included patients with the indeterminate form found no significant difference in the stroke prevalence between CD and non-CD patients (OR 3.10, 95% CI 0.89–10.77).ConclusionsCD is significantly associated with cerebrovascular events, particularly among patients with cardiomyopathy. These findings underline the need for prospective controlled studies in patients with Chagas cardiomyopathy to ascertain the prognostic significance of cerebrovascular events and to evaluate the role of therapeutic anticoagulation in primary prevention.     

NK and LAK functions in human chronic Chagas disease

Natural killer (NK) and lymphokine activated killer (LAK) functions were measured in 40 patients with chronic Chagas disease divided into asymptomatic/indeterminate (18) and symptomatic forms (22) and in 24 healthy controls. A chromium release assay was used employing K562 or P815 cell lines as targets. There was no difference in either NK or LAK activity between the three groups. A small number of patients in each group showed results above or below the normal range for controls. However, there was no correlation between NK and LAK values in the same individual. In conclusion, NK and LAK functions do not seem to be involved in the immunosuppression associated with human chronic Chagas disease.     

Trypanosoma cruzi infection in the sylvatic kissing bug Mepraia gajardoi from the Chilean Southern Pacific Ocean coast

The Southern Pacific Ocean coast has been traditionally considered a non-active transmission area for Chagas disease. In this report, we show evidence of Trypanosoma cruzi infection in the sylvatic kissing bug Mepraia gajardoi from the northern Chilean coast.     

Emerging and under-recognized Chagas cardiomyopathy in non-endemic countries

Due to recent population emigration movements,an epidemic of Chagas disease is currently menacing most developed countries.The authors report the case of a 53-year-old Brazilian woman living in Europe for the last 10 years who developed heart failure symptoms,having a previous symptomatic sinus node disease with a pacemaker implant at age of 40 years.The diagnosis was based on serology and myocardial biopsy and the patient was treated with nifurtimox.The authors emphasize the need of a high level of suspicion in patients with suggestive epidemiology and the needof populational screening of specific high risk groups.New treatment options are also discussed.     

Primer choque apropiado del desfibrilador automático implantable en pacientes con cardiopatía chagásica

Objetives:

To assess if patients with Chagasic heart disease (CHD) received effective automatic implantable defibrillator (AID) shocks earlier than patients with ischemic heart disease (IHD).

Methods:

Retrospective cohort of patients with CHD and IHD who received an implantable cardioverter defibrillator (ICD) between 2009 and 2018, in a tertiary hospital. We evaluated the time between the implant of ICD and the first effective shock in patients with CHD and compared it with the IHD control population.

Results:

We included a total of 64 patients, 20 with CHD and 44 with IHD. CHD patients presented earlier an effective shock than patients with IHD during the first year (hazard ratio [HR]: 8.4; 95% confidence interval [95% CI]: 2.09-34.02; p = 0.0027), and at three years (HR: 4.61; 95% CI: 1.51-14.07; p = 0.0072). 100% of CHD patients who received the ICD as secondary prevention of sudden cardiac death presented an effective shock during the first 26 months of follow-up.

Conclusions:

Patients with CHD received effective ICD shocks earlier than the IHD patients. All patients with CHD and ICD as secondary prevention had an appropriate ICD shock at short term, representing the highest risk population, and supporting the indication of the device in a setting where randomized clinical trials are lacking.     

PREVALENCE OF CHAGAS DISEASE AMONG BLOOD DONOR CANDIDATES IN TRIANGULO MINEIRO,MINAS GERAIS STATE,BRAZIL

Despite public health campaigns and epidemiological surveillance activities, Chagas disease remains a major health problem in Latin America. According to data from the World Health Organization, there are approximately 7-8 million people infected with Trypanosoma cruzi worldwide, a large percentage of which in Latin America. This study aims to examine the serological profile of blood donors in blood banks of Hemominas hematology center, in the town of Ituiutaba, Minas Gerais State, Brazil. The study sample consisted of 53,941 blood donors, which were grouped according to gender and age. Sample collections were performed from January 1991 to December 2011, and 277 donors (0.5%) were considered serologically ineligible due to Chagas disease. Analysis of data showed no significant difference between genders. As for age, the highest proportion of ineligible donors was from 40 to 49 years (30%), and there was a positive correlation between increasing age and the percentage of patients seropositive for Chagas disease. Therefore, adopting strategies that allow the safe identification of donors with positive serology for Chagas disease is essential to reduce or eliminate indeterminate serological results.