LEWIS FLETCHER BUSS
Projetos de Pesquisa
Unidades Organizacionais
LIM/46 - Laboratório de Parasitologia Médica, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
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- Incidence and Predictors of Progression to Chagas Cardiomyopathy: Long-Term Follow-Up of Trypanosoma cruzi-Seropositive Individuals(2021) NUNES, Maria Carmo P.; BUSS, Lewis F.; SILVA, Jose Luiz P.; MARTINS, Larissa Natany A.; OLIVEIRA, Claudia Di Lorenzo; CARDOSO, Clareci Silva; BRITO, Bruno Oliveira de Figueiredo; FERREIRA, Ariela Mota; OLIVEIRA, Lea Campos; BIERRENBACH, Ana Luiza; FERNANDES, Fabio; BUSCH, Michael P.; HOTTA, Viviane Tiemi; MARTINELLI, Luiz Mario Baptista; SOEIRO, Maria Carolina F. Almeida; BRENTEGANI, Adriana; SALEMI, Vera M. C.; MENEZES, Marcia M.; RIBEIRO, Antonio Luiz P.; SABINO, Ester CerdeiraBackground: There are few contemporary cohorts of Trypanosoma cruzi-seropositive individuals, and the basic clinical epidemiology of Chagas disease is poorly understood. Herein, we report the incidence of cardiomyopathy and death associated with T. cruzi seropositivity. Methods: Participants were selected in blood banks at 2 Brazilian centers. Cases were defined as T. cruzi-seropositive blood donors. T. cruzi-seronegative controls were matched for age, sex, and period of donation. Patients with established Chagas cardiomyopathy were recruited from a tertiary outpatient service. Participants underwent medical examination, blood collection, ECG, and echocardiogram at enrollment (2008-2010) and at follow-up (2018-2019). The primary outcomes were all-cause mortality and development of cardiomyopathy, defined as the presence of a left ventricular ejection fraction <50% or QRS complex duration 120 ms, or both. To handle loss to follow-up, a sensitivity analysis was performed using inverse probability weights for selection. Results: We enrolled 499 T. cruzi-seropositive donors (age 4810 years, 52% male), 488 T. cruzi-seronegative donors (age 49 +/- 10 years, 49% male), and 101 patients with established Chagas cardiomyopathy (age 48 +/- 8 years, 59% male). The mortality in patients with established cardiomyopathy was 80.9 deaths/1000 person-years (py) (54/101, 53%) and 15.1 deaths/1000 py (17/114, 15%) in T. cruzi-seropositive donors with cardiomyopathy at baseline. Among T. cruzi-seropositive donors without cardiomyopathy at baseline, mortality was 3.7 events/1000 py (15/385, 4%), which was no different from T. cruzi-seronegative donors with 3.6 deaths/1000 py (17/488, 3%). The incidence of cardiomyopathy in T. cruzi-seropositive donors was 13.8 (95% CI, 9.5-19.6) events/1000 py (32/262, 12%) compared with 4.6 (95% CI, 2.3-8.3) events/1000 py (11/277, 4%) in seronegative controls, with an absolute incidence difference associated with T. cruzi seropositivity of 9.2 (95% CI, 3.6-15.0) events/1000 py. T. cruzi antibody level at baseline was associated with development of cardiomyopathy (adjusted odds ratio, 1.4 [95% CI, 1.1-1.8]). Conclusions: We present a comprehensive description of the natural history of T. cruzi seropositivity in a contemporary patient population. The results highlight the central importance of anti-T. cruzi antibody titer as a marker of Chagas disease activity and risk of progression.
- Deriving a parsimonious cardiac endpoint for use in epidemiological studies of Chagas disease: results from the Retrovirus Epidemiology Donor Study-II (REDS-II) cohort(2021) BUSS, Lewis F.; BES, Taniela Marli; PEREIRA, Alexandre; NATANY, Larissa; OLIVEIRA, Claudia Di Lorenzo; RIBEIRO, Antonio Luiz P.; SABINO, Ester CerdeiraChagas cardiomyopathy (ChCM) is a severe consequence of Trypanosoma cruzi infection and has a range of electrocardiographic (ECG) and echocardiographic (ECHO) manifestations. There is a need for a standard and parsimonious research cardiac end point that does not rely on expert panel adjudication, and it is not intended to change the ChCM definition. We use data from the REDS-II cohort to propose a simplified cardiac endpoint. A total of 499 T. cruzi-seropositive blood donors were included. All participants underwent a 12-lead ECG, echocardiogram and clinical examination, and those with abnormal findings were reviewed by a panel of cardiologists who classified cases as having Chagas cardiomyopathy or not. We created an exhaustive set of ECG and ECHO finding combinations and compared these with the panel's classification. We selected the simplest combination that most accurately reproduced the panel's results. Individual ECG and ECHO variables had low sensitivity for panel-defined cardiomyopathy. The best performing combination was right bundle branch block and/or ECHO evidence of left ventricular hypocontractility. This combination had 98% specificity and 85% sensitivity for panel-defined ChCM. It was not possible to improve the overall accuracy by addition of any other ECG or ECHO variable. Substituting right bundle branch block for the more inclusive finding of QRS interval > 120 ms produced similar results. The combination of prolonged QRS interval and/or left ventricular hypocontractility closely reproduced the REDS-II expert panel classification of Chagas ChCM. In conclusion, the simple and reproducible research endpoint proposed here captures most of the spectrum of cardiac abnormalities in Chagas disease.
- Pharmacogenomic Profile and Adverse Drug Reactions in a Prospective Therapeutic Cohort of Chagas Disease Patients Treated with Benznidazole(2021) FRANCO, Lucas A. M.; MOREIRA, Carlos H. V.; BUSS, Lewis F.; OLIVEIRA, Lea C.; MARTINS, Roberta C. R.; MANULI, Erika R.; LINDOSO, Jose A. L.; BUSCH, Michael P.; PEREIRA, Alexandre C.; SABINO, Ester C.Chagas disease remains a major social and public health problem in Latin America. Benznidazole (BZN) is the main drug with activity against Trypanosoma cruzi. Due to the high number of adverse drug reactions (ADRs), BZN is underprescribed. The goal of this study was to evaluate the genetic and transcriptional basis of BZN adverse reactions. Methods: A prospective cohort with 102 Chagas disease patients who underwent BZN treatment was established to identify ADRs and understand their genetic basis. The patients were classified into two groups: those with at least one ADR (n = 73), and those without ADRs (n = 29). Genomic analyses were performed comparing single nucleotide polymorphisms between groups. Transcriptome data were obtained comparing groups before and after treatment, and signaling pathways related to the main ADRs were evaluated. Results: A total of 73 subjects (71.5%) experienced ADRs. Dermatological symptoms were most frequent (45.1%). One region of chromosome 16, at the gene LOC102724084 (rs1518601, rs11861761, and rs34091595), was associated with ADRs (p = 5.652 x 10(-8)). Transcriptomic data revealed three significantly enriched signaling pathways related to BZN ADRs. Conclusions: These data suggest that part of adverse BZN reactions might be genetically determined and may facilitate patient risk stratification prior to starting BZN treatment.
- Cohort profile update: the main and new findings from the SaMi-Trop Chagas cohort(2021) OLIVEIRA, Claudia Di Lorenzo; CARDOSO, Clareci Silva; BALDONI, Nayara Ragi; NATANY, Larissa; FERREIRA, Ariela Mota; OLIVEIRA, Lea Campos de; NUNES, Maria do Carmo Pereira; QUINTINO, Nayara Dornela; BIERRENBACH, Ana Luiza; BUSS, Lewis F.; HAIKAL, Desiree Sant'Ana; NETO, Edecio Cunha; RIBEIRO, Antonio Luiz Pinho; SABINO, Ester CerdeiraThe SaMi-Trop project is a cohort study conducted in 21 municipalities of endemic areas of Chagas disease, including 1,959 patients with chronic Chagas cardiomyopathy. In this article we updated the results of the project, adding information from the second cohort visit. Trypanosoma cruzi-seropositive patients were enrolled from the primary care Telehealth service in Minas Gerais State, Brazil. The eligibility criterium for the second visit was the participation in the baseline evaluation. Of 1,959 participants at the baseline assessment, 1,585 (79.9%) returned after two years for the second evaluation. The mortality rate was 6.7%, but varied from 0.9% to 18.2% when it was stratified by certain clinical characteristics. A lower age-adjusted NT-Pro-BNP level (less than 300) and a prior benznidazole treatment were associated with lower mortality. There was an improvement in most quality of life domain scores. Participants have also reported fewer signs and symptoms and greater use of medication. The second follow-up visit will be complete in Oct 2021.