ABSTRACT Background: Leprosy is a neglected chronic infection caused by Mycobacterium leprae, that is curable. The magnitude of the disease and severity of the debilitation it causes renders leprosy a public health problem. This study aimed to analyze the endemic profile of leprosy in the Murrupula district and evaluate the socioeconomic, clinical, and serological profiles of leprosy contacts. Methods: A cross-sectional study of patients with leprosy diagnosed between 2013 and 2017 and their household and community contacts was conducted in Murrupula District, Nampula Province, Mozambique. Interviews, simplified dermatoneurological examinations, Mycobacterium leprae flow (ML Flow) tests, and Mitsuda tests were performed. Results: Most of the leprosy cases were multibacillary. The patients had some degree of physical disability. ML Flow positivity was more common in household contacts of the patients diagnosed with leprosy and in community individuals who spontaneously presented for testing. In total, 17 patients were diagnosed with leprosy. Conclusions: This study revealed an active chain of transmission, hidden prevalence, and operational deficiencies in leprosy surveillance and care. The results suggest that the implementation of a public health policy for leprosy prevention and control in Nampula Province is necessary. In future, the possibility of expanding the policy to the entire country should be considered.

ABSTRACT Background: The epidemic curve has been obtained based on the 7-day moving average of the events. Although it facilitates the visualization of discrete variables, it does not allow the calculation of the absolute variation rate. Recently, we demonstrated that the polynomial interpolation method can be used to accurately calculate the daily acceleration of cases and deaths due to COVID-19. This study aimed to measure the diversity of epidemic curves and understand the importance of socioeconomic variables in the acceleration, peak cases, and deaths due to COVID-19 in Brazilian states. Methods: Epidemiological data for COVID-19 from federative units in Brazil were obtained from the Ministry of Health’s website from February 25 to July 11, 2020. Socioeconomic data were obtained from the Instituto Brasileiro de Geografia e Estatística (https://www.ibge.gov.br/). Using the polynomial interpolation methods, daily cases, deaths and acceleration were calculated. Moreover, the correlation coefficient between the epidemic curve data and socioeconomic data was determined. Results: The combination of daily data and case acceleration determined that Brazilian states were in different stages of the epidemic. Maximum case acceleration, peak of cases, maximum death acceleration, and peak of deaths were associated with the Gini index of the gross domestic product of Brazilian states and population density but did not correlate with the per capita gross domestic product of Brazilian states. Conclusions: Brazilian states showed heterogeneous data curves. Population density and socioeconomic inequality were correlated with a more rapid exponential growth in new cases and deaths.

ABSTRACT Chronic Chagas Cardiomyopathy (CCC) is the most prevalent type of myocarditis and the main clinical form of the Chagas disease, which has peculiarities such as focal inflammation, structural derangement, hypertrophy, dilation, and intense reparative fibrosis. Many cellular compounds contribute to CCC development. Galectin-3 is a partaker in inflammation and contributes to myocardial fibrosis formation. Some studies showed the connection between Galectin-3 and fibrosis in Chagas disease but are still inconclusive on the guidance for the early implementation of pharmacological therapy. This systematic review evaluated Galectin-3 as a biomarker for fibrosis intensity in CCC. Two independent reviewers have searched five databases (PubMed, EMBASE, Cochrane Library, Scopus, and Lilacs), using the following search terms: galectin-3, biomarkers, fibrosis, Chagas cardiomyopathy, and Chagas disease. Overall, seven studies met the inclusion criteria and made up this review. There were four trials conducted through animal model experiments and three trials with humans. Experimental data in mice indicate an association between Galectin-3 expression and fibrosis in CCC (75% of studies). Data from human studies showed no direct connection between myocardial fibrosis and Galectin-3 expression (80% of studies). Thus, human findings do not provide significant evidence indicating that Galectin-3 is related to fibrosis formation in Chagas disease. Based on the analyzed studies, it is suggested that Galectin-3 might not be a good fibrosis marker in CCC.

ABSTRACT Patients with Chagas disease have reduced health-related quality of life (HRQoL). Hence, we aimed to identify the factors that mostly affected their HRQoL. This was a systematic review of qualitative studies. The Latin American and Caribbean Health Sciences Literature, Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, Web of Science, and SciVerse Scopus databases were searched for relevant studies without language or date restrictions. The search and data analysis were performed by independent reviewers; all qualitative studies that reported the factors that had an impact on the HRQoL of patients with Chagas disease were included. The risk of bias was assessed using the Critical Appraisal Skills Program Qualitative Study Checklist; confidence in the evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative approach. Five studies were included in this review: four in Brazil and one in California, United States, with immigrants from Central and South America. The sample consisted of 207 patients with chronic Chagas disease. Stigma, physical limitations, work absenteeism, emotional or mental aspects, fear of treatment, and fear of the future had the strongest impact on the HRQoL. All items showed moderate confidence except for fear of treatment (low confidence). The physical, emotional, mental, and cultural aspects affected the HRQoL of patients with chronic Chagas disease. Identification of these factors is important in the development of strategies aimed at improving the HRQoL of this population.

ABSTRACT People who interact with leprosy patients in their environment, neighborhood, family, or social relationships are at risk to develop the disease. This systematic review investigated the risk and protective factors associated with the development of leprosy in Brazilian contacts. The studies were found in Cochrane Library, PubMed (MEDLINE), Embase, Virtual Health Library, grey literature and hand search until July 2021. The study selection, data extraction and quality assessment were independently performed by two investigators. The quality assessment was performed using the Newcastle-Ottawa Scale (NOS). This review was registered in PROSPERO (CRD42020160680). Seventeen articles fulfilled the inclusion criteria (n=544). The immunological and molecular factors, such as Anti-phenolic Glycolipid Antibodies (Anti-PGL-1) seropositivity, negative Mitsuda test, absence of Bacillus Calmette-Guérin (BCG) scar, positive Polymerase Chain Reaction (PCR) in blood; age and race; conviviality, education, contact time and type of contact, as well as elements related to the index case (bacilloscopic index; genetic conditions, family relationships), and some combined factors were shown to be relevant risk factors associated with the development of the disease in Brazilian leprosy contacts. The protective factors reported were the presence of one or more BCG scars, positive Mitsuda test, and education level. All selected studies were considered of high quality according to NOS. The knowledge of disease-related risk and protective factors provides the scientific basis for decision-making in the management of the disease in leprosy contacts.

Abstract INTRODUCTION: Chagas cardiomyopathy (ChC) is highly stigmatized, and the presence of depressive symptoms may be a common feature. However, its determinants remain unclear. Therefore, the present study aimed to verify the prevalence of depression and the clinical, echocardiographic, functional, and quality of life factors associated with depressive symptoms in patients with ChC and predominantly preserved cardiac function. METHODS: Thirty-five patients with ChC (aged 40 to 60 years, 66% men, NYHA I-III) were evaluated by echocardiography, cardiopulmonary exercise testing, 6-minute walk test (6MWT), and Mini-Mental State Examination. Physical activity level was assessed using the Human Activity Profile (HAP) and health-related quality of life was assessed using the Short-Form Health Survey (SF-36). Depressive symptoms were evaluated using the Beck Depression Inventory. A cutoff point greater than 9 was indicative of depression. RESULTS: Depression was detected in 13 patients (37%). In the univariate analysis, female sex, NYHA functional class, body mass index, HAP score, mental summary of SF-36, peak oxygen uptake, and 6MWT distance were associated with depressive symptoms. The final model showed that only the HAP score (B = -0.533; 95% confidence interval [CI]: -0.804 to -0.262) and SF-36 mental summary (B = -0.269; 95% CI: -0.386 to -0.153) remained as independent predictors of depressive symptoms in patients with ChC. CONCLUSIONS: Depression was prevalent in patients with ChC and predominantly preserved cardiac function. Physical activity and mental health were independent risk factors for depressive symptoms.

Abstract Patients with Chagas cardiomyopathy (ChC) usually progress with fatigue and dyspnea. Exercise tests are valuable for the functional evaluation of these patients. However, information about the applicability of the exercise tests is scattered, and no studies have systematically reviewed the results. Thus, the present review explored the general aspects and prognostic value of exercise tests in patients with ChC. A literature search of the MEDLINE, Web of Science, CINAHL, Scopus, and LILACS databases was performed to identify relevant studies. There were no data restrictions, and articles that met the objective of the study were selected. Articles written in English, Portuguese, and Spanish were considered, and 25 articles were finally included. The peak oxygen uptake (VO2peak) was correlated with demographic and echocardiographic variables. Echocardiographic features of the left ventricular diastolic function and right ventricular systolic function appeared to be determinants of functional capacity, in addition to age and sex. VO2peak was associated with higher mortality, especially in patients with dilated ChC. The minute ventilation/carbon dioxide production slope (VE/VCO2 slope) was a strong predictor of survival; however, more studies are needed to verify this observation. Field tests showed moderate to strong correlation with VO2peak and thus may be inexpensive tools for the functional evaluation of patients with ChC. However, few studies have verified their prognostic significance. While exercise tests are useful tools for functional assessment, information is scarce regarding further considerations, and many of the criteria are based on guidelines for other heart diseases.

Abstract INTRODUCTION: The acceleration of new cases is important for the characterization and comparison of epidemic curves. The objective of this study was to quantify the acceleration of daily confirmed cases and death curves using the polynomial interpolation method. METHODS: Covid-19 epidemic curves from Brazil, Germany, the United States, and Russia were obtained. We calculated the instantaneous acceleration of the curve using the first derivative of the representative polynomial. RESULTS: The acceleration for all curves was obtained. CONCLUSIONS: Incorporating acceleration into an analysis of the Covid-19 time series may enable a better understanding of the epidemiological situation.

We aimed to investigate the association of CD14 -260C/T (rs2569190) polymorphism and Chagas cardiomyopathy and the functional characteristics of CD14+ and CD14- monocytes upon infection with Trypanosoma cruzi. We observed an association between the T- genotype (absence of allele -260T) related to low CD14 expression and the dilated cardiomyopathy type of Chagas disease. Furthermore, we observed that CD14- monocytes showed a more activated profile upon in vitro infection with T. cruzi than CD14+ monocytes. Our findings suggest that T- genotype is associated with susceptibility to develop Chagas dilated cardiomyopathy, likely linked to the T. cruzi-induced inflammatory profile of CD14- monocytes.

Resumo A alteração do metabolismo do ferro na insuficiência cardíaca (IC) tem sido descrita como um importante marcador prognóstico. Verificar se os marcadores da cinética do ferro guardam relação com a morbidade e a etiologia da cardiomiopatia chagásica. Pacientes com cardiomiopatia chagásica crônica (CCC, n = 40), com a forma indeterminada (IND, n = 40), além de cardiomiopatia não chagásica (NCh, n = 40). A idade média foi de 50,98 ± 5,88 no CCC, 50% eram do sexo masculino, 49,68 ± 5,28 no IND, 52,2% eram do sexo masculino e 49,20 ±10,09 no NCh, 12,5% eram do sexo masculino. Observaram-se níveis de ferro (FeSe) menores no grupos CCC (93,15 ± 36,53), quando comparados ao IND (125,30 ± 22,79) e NCh (114,77 ± 18,90) (p = 0,0004), índice de saturação de transferrina (IST) menor no CCC (29,48 ± 6,59), quando comparado ao IND (30,95 ± 7,06) e no grupo NCh (39,70 ± 7,54) (p= 0,0001), capacidade total de ligação do ferro CTLF menor no grupo CCC (297,30 ± 36,46), quando comparado ao grupo IND (196,52 ± 56,95) e ao grupo NCh (275,18 ± 33,48) (p = 0,0001), ferritina menor no grupo CCC (134,55, 1,56-42,36), quando comparada ao grupo IND (156,25, 1,72 - 42,20) e ao grupo NCh (112,95, 2,88-42,66) (p = 0.0004). Verificou-se também que o FeSe (IC% 95% 1,00-1,04; p = 0,0014), o IST (IC 95% 1,02-1,22) (p = 0,0012) e o sexo (IC 95% 1,07-14,43 p = 0,0038) associaram-se independentemente ao grau de disfunção ventricular na cardiomiopatia chagásica. Os pacientes com CCC demonstraram maior alteração no metabolismo do ferro em relação a forma indeterminada e outras formas de miocardiopatias.

Abstract Changes in iron metabolism in heart failure (HF) have been described as an important prognostic marker. To check if the markers of iron kinetics are related to the morbidity and etiology of chagasic cardiomyopathy. Patients with Chronic Chagasic Cardiomyopathy (CCC, n = 40), with indeterminate form (IND, n = 40), besides non-chagasic cardiomyopathy (NCh, n = 40). The mean age was 50.98 ± 5.88 in CCC, 50% were male, 49.68 ± 5.28 in IND, 52.2% were male, and 49.20 ± 10.09 in NCh, 12.5% were male. Lower levels of iron (FeSe) were observed in the CCC groups (93.15 ± 36.53), when compared to IND (125.30 ± 22.79) and NCh (114.77 ± 18.90) (p = 0.0004), lower IST transferrin saturation index in CCC (29.48 ± 6.59), when compared to IND (30.95 ± 7.06) and in the NCh group (39.70 ± 7.54) p = 0.0001), total binding capacity of the lower CTLF iron in the CCC group (297.30 ± 36.46), when compared to the IND group (196.52 ± 56.95) and the NCh group (275.18 ± 33, 48) (p = 0.0001), lower ferritin in the CCC group (134.55, 1.56-42.36), when compared to the IND group (156,25, 1,72-42,20) and the NCh group (112.95, 2.88-42.66) (p = 0.0004). It was also observed that FeSe (95% CI 1.00-1.04, p = 0.0014), IST (95% CI 1.02-1.22) (p = 0.0012) and gender (95% CI 1.07-14.43 p = 0.0038) were independently associated with the degree of ventricular dysfunction in chagasic cardiomyopathy. CCC patients showed greater change in iron metabolism regarding the indeterminate form and other forms of cariomyopathies.

ABSTRACT The present study sought to investigate the risk factors for physical disability upon release from multidrug therapy (MDT) in new cases of leprosy, registered at a referral center in Brazil. This is a longitudinal and retrospective study that evaluated 260 patients. Multivariate analyses, using both the ordinal logistic regression, as well as the classification and regression tree (CART) algorithm were performed to determine the factors associated with physical disability upon release from treatment. The prevalence of disability did not differ significantly between diagnosis and release from treatment. Number of affected nerves and sensory impairment upon diagnosis were risk factors for disability at the end of MDT. The analysis using the CART algorithm resulted in the development of a clinical score to predict the risk of disability upon release from MDT. The decision tree may have a direct applicability in clinical practice for professionals dealing with leprosy, as it allows them to identify patients with a higher risk of physical disability through the use of simple and widely available clinical tests. This study also shows that the disability grade upon admission is the main risk factor for disability upon release from MDT. This result draws attention to the importance of early diagnosis in disability prevention.

ABSTRACT The Mitsuda test is a skin test based on the individual’s immune response through late and highly specific hypersensitivity reaction to the Mycobacterium leprae bacillus. A negative reaction identifies individuals who present a higher risk of becoming ill if exposed to M. leprae and, if they become ill, to develop the virchowian form of disease. The Mitsuda test reading is performed by means of a millimeter ruler. The dermatoscopy is a method that has not been used in the evaluation of cutaneous tests, although its use has increased in several areas. The study aimed to compare the results between the standardized reading and the total area of the Mitsuda test obtained by a computerized method which was structured by the association of digital dermatoscopy, the Dermatology Web system and the Image Tool 3.0 software. Data collection was performed at the Dermatology Outpatient Clinic of the Eduardo de Menezes Hospital, in Belo Horizonte, from November 2015 to August 2016. The sample consisted of 100 leprosy domiciliary contacts. There was an excellent agreement between the Mitsuda test (diameter and area), with a coefficient greater than 80%, and an excellent correlation with the Spearman’s correlation coefficient (0.936). The intraclass correlation coefficient indicated a low (0.219) but significant agreement between the two measurements. In conclusion, there is a significant correlation between the standardized reading and the total area of the Mitsuda test. Digital dermoscopy can be an alternative instrument of evaluation, allowing the computerization and recording of the Mitsuda test.

Abstract Reduced peak oxygen uptake (VO2peak) is a common clinical finding in progressive Chagas disease. However, the disease stage in which functional impairment is detectable remains uncertain. The present study compared functional capacity between healthy controls and patients with different clinical forms of Chagas disease. A systematic review and meta-analysis (PROSPERO database CRD42017058353) was conducted following a search of the MEDLINE, Web of Science, CINAHL, and LILACS databases from September to December 2017 for articles published in English, Spanish, or Portuguese, with no date restrictions. We included studies that compared the VO2peak between healthy and Chagas disease patients, stratified according to 3 clinical forms [no apparent cardiac disease, non-dilated Chagas heart disease (CHD), and dilated CHD]. Seven cross-sectional studies were included. Chagas disease patients without apparent cardiac disease (n=208) had VO2peak values [mean difference, -1.55ml/kg/min; 95% confidence interval (CI), -4.98ml/kg/min to 1.88ml/kg/min] similar to those of healthy controls (n=105; p=0.38, I2=52%). In non-dilated CHD (n=159), VO2peak was 8.71ml/kg/min lower (95% CI, -13.99 to -3.42ml/kg/min) than in healthy controls (n=59; p=0.001, I2=75%). VO2peak was also significantly lower (mean difference, -9.30ml/kg/min; 95% CI, -11.34 to -7.25ml/kg/min) in dilated CHD patients (n=131) than in healthy controls (n=53; p<0.001, I2=0%). Exercise capacity in Chagas disease patients without apparent cardiac disease is similar to that in healthy controls. Functional impairment in Chagas disease is detectable in the early stages of cardiac involvement, even in the absence of systolic dysfunction and signs of heart failure.

ABSTRACT The vasoactive intestinal peptide (VIP) expression is lower in cardiac chagasic patients and is related to worse cardiac function. The reduction of VIP in patients with Chagas disease may be a result of its enhanced degradation. To test this hypothesis, the tryptase and chymase expression was evaluated. We also related VIP levels with interleukin-17 (IL-17) expression since VIP may modulate IL-17 production. Plasma levels of chymase were higher in chagasic patients. Conversely, VIP/chymase and VIP/tryptase ratios were lower in chagasic patients when compared to non-infected individuals. Besides, the VIP/chymase ratio was lower in chagasic cardiac patients in comparison with the indeterminate group. A positive correlation between tryptase and chymase levels was observed in chagasic cardiac patients. In relation to IL-17, we observed a higher expression of this cytokine in the cardiac form of the disease than in the indeterminate form. IL-17/VIP ratio was higher in the cardiac form in comparison with non-infected or indeterminate form. These results suggest that the low levels of VIP observed in chagasic patients could be due to an increased production of chymase and/or to the additive effect of the interaction between chymase and tryptase in the cardiac form. Moreover, the decreased VIP expression may contribute to the increase of IL-17 in chagasic cardiac patients.