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OBJECTIVE: To analyze the survival of patients with Chagas disease, beneficiaries of social security and social assistance, in Brazil, from 1942 to 2016. METHODS: This is a retrospective cohort study with data from the Brazilian Ministry of Social Security. The event of interest was death, and the survival functions were estimated by the Kaplan-Meier and Cox regression methods. RESULTS: In the period "onset of the disease until death", women (HR=0.54; 95%CI 0.43-0.53) and receiving social security benefits (HR=0.13; 95%CI 0.11-0.23) were associated with longer survival. Lower survival was associated with the cardiac form of the disease (HR=2.64; 95%CI 2.23-3.12), living in a rural area (HR=1.23; 95%CI 1.14-1.21), and manifestation of the disease between the years 2000 and 2016 (HR=5.32; 95%CI 4.74-5.93). Likewise, in the period "work disability until death", women (HR=0.51; 95%CI 0.41-0.52) and receiving social security benefits (HR=0.24; 95%CI 0,14-0.45) were associated with longer survival, as well as the cardiac form of the disease (HR=1.95; 95%CI 1.83-2.13), living in a rural area (HR=1.31; 95%CI 1.21-1.54), and manifestation of the disease between 2000 and 2016 (HR=1.53; 95%CI 1.33-1.71) were associated with lower survival. CONCLUSION: The main predictors of mortality and survival of patients with Chagas disease who receive social security and assistance benefits in Brazil were presented. These findings can guide the definition of priorities for follow-up actions by Primary Health Care, currently recommended for the longitudinal management of the disease.
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Doença de Chagas , Previdência Social , Humanos , Brasil/epidemiologia , Previdência Social/estatística & dados numéricos , Feminino , Masculino , Estudos Retrospectivos , Doença de Chagas/mortalidade , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Idoso , Análise de Sobrevida , Criança , Estimativa de Kaplan-Meier , Pré-Escolar , Lactente , Fatores de Tempo , Modelos de Riscos Proporcionais , Distribuição por SexoRESUMO
Chagas disease (CD) is a neglected parasitic zoonotic disease that affects over 6 million people worldwide. We conducted a retrospective study to analyze the spatiotemporal trends and risk factors for hospitalization rates of CD with cardiac and digestive diagnoses in Chile. We used the Mann-Kendall analysis for temporal trends, Global Moran's Index, and Local Indicators of Spatial Association to identify spatial autocorrelation, and regression models to determine the risk factors associated with in-hospital mortality and surgical intervention. Between 2010 and 2020, a total of 654 hospitalizations were reported, corresponding to 527 individuals. The hospitalization rate steadily decreased over the years (t = -0.636; p = 0.009). The Global Moran's I for the study period showed a positive spatial autocorrelation for hospitalization municipality and for residence municipality of CD patients (I = 0.25, p<0.001 and I = 0.45, p<0.001 respectively), indicating a clustering of hospitalizations in northern municipalities. The most frequent diagnosis was a chronic CD with digestive system involvement (55.8%) followed by a chronic CD with heart involvement (44.2%). The highest percentage of hospital discharges was observed among males (56.9%) and in the 60-79 age group (52.7%). In-hospital mortality risk was higher with increasing age (OR = 1.04), and in patients with cardiac involvement (OR = 2.3), whereas factors associated with the risk of undergoing a surgical intervention were sex (OR = 1.6) and diagnosis of CD with digestive involvement (OR = 4.4). The findings of this study indicate that CD is still a significant public health burden in Chile. Efforts should focus on improving access to timely diagnoses and treatment, reducing disease progression and hospitalization burden, and supporting clinicians in preventing complications and deaths.
Assuntos
Doença de Chagas , Mortalidade Hospitalar , Hospitalização , Análise Espaço-Temporal , Humanos , Chile/epidemiologia , Masculino , Feminino , Doença de Chagas/mortalidade , Doença de Chagas/epidemiologia , Hospitalização/estatística & dados numéricos , Fatores de Risco , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Idoso , Doença Crônica , Adulto Jovem , Adolescente , Idoso de 80 Anos ou mais , CriançaRESUMO
INTRODUCCIÓN: Las zoonosis son enfermedades transmitidas desde un hospedador animal al ser humano o viceversa. En Chile, las zoonosis de Notificación Obligatoria (NO) son: brucelosis, carbunco, triquinosis, hidatidosis, leptospirosis, dengue, enfermedad de Chagas, hantavirosis y rabia. OBJETIVO: Evaluar la tendencia y caracterizar la mortalidad por zoonosis de NO en Chile entre 1997-2018. METODOLOGÍA: Estudio ecológico de la mortalidad por zoonosis de NO. Se utilizaron bases de mortalidad y población oficiales. Se describió la mortalidad relativa, general y específica, según variables sociodemográficas. Se calcularon tasas de mortalidad anuales brutas (TMb) y ajustadas (TMa, método directo). Se evaluó la tendencia temporal con modelos de regresión de Prais-Winsten. Resultados: Entre 1997 y 2018 la mortalidad por zoonosis de NO correspondió al 0,12% (2.359 muertes) de la mortalidad total, siendo las principales causas la enfermedad de Chagas (59,8%), hidatidosis (23,9%) y hantavirosis (13,8%). La TMa general disminuyó significativamente (B: -0,017; IC95%: -0,024; -0,009) al igual que hidatidosis (B: -0,011; IC95%: -0,013; -0,008), sólo hantavirosis mostró un aumento (no significativo). CONCLUSIÓN: La mortalidad por zoonosis de NO disminuyó durante el período estudiado; solo la hantavirosis mostró un aumento en su tendencia. Se sugiere enfocar estrategias para prevenir la transmisibilidad y mortalidad por hanta, así como mejorar el acceso a tratamiento para las otras zoonosis.
BACKGROUND: Zoonoses are diseases transmitted from an animal host to humans or vice versa. In Chile, the zoonoses of mandatory notification are brucellosis, anthrax, trichinosis, hydatidosis, leptospirosis, dengue, Chagas disease, hantavirosis and rabies. AIM: To assess the trend and characterize the mortality from zoonoses of mandatory notification in Chile between 1997-2018. METHODS: An official mortality and population data were used. Relative, general and specific mortality rates were described according to sociodemographic variables. Crude and adjusted annual mortality rates (direct method) were calculated. Temporal trend was evaluated with the Prais-Winsten regression model. RESULTS: Between 1997 and 2018, the mortality rate due to zoonosis of mandatory notification corresponded to 0.13% (2152 deaths) of the total mortality, being Chagas disease (59.2%), hydatidosis (24.6%) and hantavirosis (13.5%) the main causes. The general adjusted mortality rate decreased significantly (B: -0.017; IC95%: -0.024; -0.009) as did hydatidosis (B: -0.011; IC95%: -0.013; -0.008), and only hantavirosis showed an increase trend (not significant). CONCLUSION: Mortality due to zoonoses decreased during the period; only hantavirosis showed an increasing trend. It is suggested to focus on strategies to prevent contagion and mortality by hantavirosis, as well as to improve access to treatment for the other zoonoses.
Assuntos
Humanos , Animais , Zoonoses/mortalidade , Raiva/mortalidade , Triquinelose/mortalidade , Brucelose/mortalidade , Chile/epidemiologia , Doença de Chagas/mortalidade , Infecções por Hantavirus/mortalidade , Notificação de Doenças , Dengue/mortalidade , Equinococose/mortalidade , Estudos EcológicosRESUMO
OBJECTIVE: Chagas disease (CD) globalization facilitated the co-infection with Human Immunodeficiency Virus (HIV) in endemic and non-endemic areas. Considering the underestimation of Trypanosoma cruzi (T. cruzi)-HIV co-infection and the risk of life-threatening Chagas Disease Reactivation (CDR), this study aimed to analyze the major co-infection clinical characteristics and its mortality rates. METHODS: This is a cross-sectional retrospective multicenter study of patients with CD confirmed by two serological or one parasitological tests, and HIV infection confirmed by immunoblot. CDR was diagnosed by direct microscopy with detection of trypomastigote forms in the blood or other biological fluids and/or amastigote forms in inflammatory lesions. RESULTS: Out of 241 patients with co-infection, 86.7% were from Brazil, 47.5% had <200 CD4+ T cells/µL and median viral load was 17,000 copies/µL. Sixty CDR cases were observed. Death was more frequent in patients with reactivation and was mainly caused by CDR. Other causes of death unrelated to CDR were the manifestation of opportunistic infections in those with Acquired Immunodeficiency Syndrome. The time between the co-infection diagnosis to death was shorter in patients with CDR. Lower CD4+ cells count at co-infection diagnosis was independently associated with reactivation. Similarly, lower CD4+ cells numbers at co-infection diagnosis and male sex were associated with higher lethality in CDR. Additionally, CD4+ cells were lower in meningoencephalitis than in myocarditis and milder forms. CONCLUSION: This study showed major features on T. cruzi-HIV co-infection and highlighted the prognostic role of CD4+ cells for reactivation and mortality. Since lethality was high in meningoencephalitis and all untreated patients died shortly after the diagnosis, early diagnosis, immediate antiparasitic treatment, patient follow-up and epidemiological surveillance are essentials in T. cruzi/HIV co-infection and CDR managements.
Assuntos
Doença de Chagas/mortalidade , Coinfecção/mortalidade , Atenção à Saúde , Infecções por HIV/mortalidade , Terapia de Imunossupressão , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/mortalidade , Adulto , Brasil/epidemiologia , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos , Doença de Chagas/parasitologia , Coinfecção/parasitologia , Estudos Transversais , Gerenciamento de Dados , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trypanosoma cruzi , Carga ViralRESUMO
Chagas disease remains an important public health problem with high morbidity and mortality in several Latin American countries. This nationwide population-based ecological study analyzes the epidemiological characteristics and time trends of Chagas disease-related mortality in Brazil, 2000-2019. We included all deaths reported in Brazil in which Chagas disease was mentioned in the death certificate either as an underlying or associated cause of death (multiple causes of death). Crude and age-adjusted mortality rates (per 100,000 inhabitants) were calculated and time trends analysis was performed using joinpoint regression models. In the study period, a total of 22,663,092 deaths were recorded in Brazil. Chagas disease was identified in 122,291 deaths (0.54%), 94.788 (77.5%) as an underlying cause and 27,503 (22.5%) as an associated cause. Average annual age-adjusted mortality rate was 3.22 deaths/100,000 inhabitants (95% confidence interval [CI]: 3.14-3.30). Chronic Chagas disease with cardiac involvement was the predominant clinical presentation mentioned. The highest mortality rates were observed in males, age group ≥80 years, black race/skin color, schooling 1-3 years of study, and residents in the Central-West region. Age-adjusted mortality rates showed a significant declining trend at the national level in the period (Average Annual Percent Change: -3.1%; 95% CI: -3.3; -3.0), with different local patterns and a more pronounced reduction in important endemic areas in the past. The findings show that, despite a consistent decline in mortality rates in Brazil over the study period, Chagas disease remains an important and neglected cause of death in the country, showing a marked regional variation that has social and health care implications. In addition to the control measures for disease transmission, it is necessary to guarantee access, coverage, and quality of health care to Chagas disease patients, seeking to prevent the occurrence of severe forms and deaths from the disease.
Assuntos
Doença de Chagas/epidemiologia , Adulto , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Doença de Chagas/mortalidade , Escolaridade , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: To describe the clinical and sociodemographic characteristics of participants as well as discontinuation and mortality rates in a cardiac rehabilitation programme (CRP) tailored to Chagas disease (CD). METHODS: Participants underwent functional capacity, anthropometry and cardiac function evaluations before beginning a CRP. Univariate and multivariate Cox proportional hazards models were performed to investigate the associations between clinical and sociodemographic characteristics at baseline with discontinuation rates and deaths. RESULTS: Forty-two patients were enrolled in the CRP (61.9% men, mean age of 58.1 ± 11.8 years). During a median follow-up period of 10.8 months, 74% discontinued and 14% died while enrolled in CRP. 34% of the patients who discontinued CRP died during follow-up. White race (HR = 0.09; 95% CI 0.01-1.00), right ventricular systolic dysfunction (HR = 10.54; 95% CI 1.24-89.50) and oxygen pulse (HR = 0.69; 95% CI 0.48-0.99) were independently associated with death while enrolled in CRP. Married status (HR = 0.44; 95% CI 0.21-0.95) was independently associated with discontinuation rates from CRP. VO2 peak (HR = 0.85; 95% CI 0.74-0.98) and CRP discontinuation due to CD-related reasons (HR = 8.33; 95% CI 1.91-36.27) were the variables independently associated with death after discontinuation of CRP. CONCLUSION: In this population, sociodemographic aspects and severity of CD were important determinants of CRP discontinuation and mortality.
OBJECTIFS: Décrire les caractéristiques cliniques et sociodémographiques des participants ainsi que les taux d'abandon et de décès dans un programme de réadaptation cardiaque (PRC) adapté à la maladie de Chagas (MC). MÉTHODES: Les participants ont subi des évaluations de la capacité fonctionnelle, de l'anthropométrie et de la fonction cardiaque avant de commencer un PRC. Des modèles de risques proportionnels de Cox univariés et multivariés ont été appliqués pour étudier les associations entre les caractéristiques cliniques et sociodémographiques au départ avec les taux d'abandon et les décès. RÉSULTATS: 42 patients ont été enrôlés dans le PRC (61,9% d'hommes, âge moyen de 58,1 ± 11,8 ans). Au cours d'une période médiane de suivi de 10,8 mois, 74% ont abandonné et 14% sont décédés durant leur enrôlement au PRC. 34% des patients qui ont arrêté le PRC sont décédés au cours du suivi. La race blanche (HR = 0,09; IC95%: 0,01-1,00), le dysfonctionnement systolique ventriculaire droite (HR = 10,54; IC95%: 1,24-89,50) et le pouls d'oxygène (HR = 0,69; IC95%: 0,48-0,99) étaient indépendamment associés avec le décès lors de l'enrôlement au PRC. Le statut marié (HR = 0,44; IC95%: 0,21-0,95) était indépendamment associé aux taux d'abandon de la CRP. Le pic de VO2 (HR = 0,85; IC95%: 0,74-0,98) et l'arrêt du PRC pour des raisons liées à la MC (HR = 8,33; IC95%: 1,91 à 36,27) étaient les variables indépendamment associées au décès après l'arrêt du PRC. CONCLUSION: Dans cette population, les aspects sociodémographiques et la sévérité de la MC étaient des déterminants importants de l'arrêt du PRC et du décès.
Assuntos
Reabilitação Cardíaca/mortalidade , Doença de Chagas/mortalidade , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Idoso , Brasil/epidemiologia , Doença de Chagas/classificação , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Socioeconômicos , Análise de Sobrevida , Centros de Atenção TerciáriaRESUMO
Abstract Background The importance of regional sympathetic denervation in the pathophysiology and prognosis of Chagas disease has been recognized. Objective To conduct a review of studies that have assessed dysautonomia in chronic Chagas heart disease. Methods The search was performed on the Medline, Pubmed, Lilacs and SciELO databases. The inclusion criteria were: original articles published in full; studies on individuals with Chagas disease, that used diagnostic methods for chagasic cardiomyopathy, and had clear inclusion and exclusion criteria. Duplicate studies, studies including children (0 to 10 years old), studies involving animals, in vitro experiments, case reports, editorials, theses, and dissertations were excluded. Results A total of 281 articles were retrieved, and 10 met the inclusion criteria and were analyzed. There was great heterogeneity as to the technique for assessing dysautonomia, groups of patients studied and classification of Chagas disease. The methods used for studying the autonomic system was immunohistochemistry (n=1), Valsalva and tilt-test (n=1), scintigraphy (n=6) and Holter monitoring (n=2). The results indicated dysautonomia in the indeterminate, digestive and cardiac forms of Chagas disease, and sympathetic denervation in the indeterminate and cardiac forms of the disease. There was agreement between areas of denervation, hypoperfusion and fibrosis, but areas of denervation were larger than those of hypoperfusion. The frequency of denervation and its extension increased from the indeterminate to the cardiac form. There was an association between extension of denervation and previous history of malignant ventricular arrhythmia. Conclusions The evidence presented in this review supports that an early diagnosis of autonomic denervation in chronic Chagas' disease allows the identification of patients with an increased risk of sudden death. Int J Cardiovasc Sci. 2020; [online].ahead print, PP.0-0
Assuntos
Cardiomiopatia Chagásica/complicações , Doença de Chagas/diagnóstico , Disautonomias Primárias/complicações , Disautonomias Primárias/diagnóstico , Sistema Nervoso Autônomo , Doença de Chagas/mortalidade , Diagnóstico PrecoceRESUMO
Chagas disease (CD) is a neglected disease and endemic in Brazil. In the Brazilian Northeast Region, it affects millions of people. Therefore, it is necessary to identify the spatiotemporal trends of CD mortality in the Northeast of Brazil. This ecological study was designed, in which the unit of analysis was the municipality of the Brazilian northeast. The data source was the Information System of Mortality. It was calculated relative risk from socioeconomic characteristics. Mortality rates were smoothed by the Local Empirical Bayes method. Spatial dependency was analysed by the Global and Local Moran Index. Scan spatial statistics were also used. A total of 11 287 deaths by CD were notified in the study. An expressive parcel of this number was observed among 70-year-olds or more (n = 4381; 38.8%), no schooling (n = 4381; 38.8%), mixed-race (n = 4381; 62.3%), male (n = 6875; 60.9%). It was observed positive spatial autocorrelation, mostly in municipalities of the state of Bahia, Piauí (with high-high clusters), and Maranhão (with low-low clusters). The spatial scan statistics has presented a risk of mortality in 24 purely spatial clusters (P < 0.05). The study has identified the spatial pattern of CD mortality mostly in Bahia and Piauí, highlighting priority areas in planning and control strategies of the health services.
Assuntos
Doença de Chagas/mortalidade , Doenças Endêmicas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Análise Espaço-Temporal , Adulto JovemRESUMO
OBJECTIVE: To analyse spatial patterns and the temporal tendency of mortality related to Chagas disease, in order to identify priority control areas in the state of Sergipe, Northeast Brazil. METHODS: We conducted an ecological and time-series study with spatial analysis techniques on deaths from Chagas disease in the state of Sergipe (1996-2016). We used data from the Mortality Information System (SIM). The temporal analysis was performed using a statistical technique capable of describing changes in the trend pattern for the period. Thematic maps were elaborated from point and polygonal analyses. RESULTS: There were 247 deaths related to Chagas disease, with a mean of 11.7 deaths/year, most of them male (64%), and aged 50-59 years (21%) and 60-69 years (26%). Two segments with increasing, non-constant and significant trends were identified: 1996-2005 (APC = 21.6%; P = 0.01) and 2005-2016 (APC = 4.4%; P = 0.01), with APPC = 11.8% (P = 0.01). A positive and significant spatial autocorrelation with areas of higher risk of death was found in the southern region of the state. CONCLUSIONS: The trend of mortality related to Chagas disease in the state of Sergipe was increasing during the period analysed, with a heterogeneous distribution of cases. A main risk area was identified in the southern region of the state.
OBJECTIF: Analyser les profils spatiaux et la tendance temporelle de la mortalité liée à la maladie de Chagas, afin d'identifier les domaines de priorité de lutte dans l'Etat de Sergipe, dans le nord-est du Brésil. MÉTHODES: Nous avons mené une étude écologique et de séries chronologiques avec des techniques d'analyse spatiale sur les décès dus à la maladie de Chagas dans l'état de Sergipe (1996-2016). Nous avons utilisé les données du système d'information sur la mortalité (SIM). L'analyse temporelle a été réalisée à l'aide d'une technique statistique capable de décrire les changements dans le profil de tendance pour la période. Des cartes thématiques ont été élaborées à partir d'analyses ponctuelles et polygonales. RÉSULTATS: Il y a eu 247 décès liés à la maladie de Chagas, avec une moyenne de 11,7 décès/an, pour la plupart de sexe masculin (64%), et âgés de 50 à 59 ans (21%) et de 60 à 69 ans (26%). Deux segments avec des tendances à la hausse, non constantes et significatives ont été identifiés: 1996-2005 (APC = 21,6%; p = 0,01) et 2005-2016 (APC = 4,4%; p = 0,01), avec APPC = 11,8% (p = 0,01). Une autocorrélation spatiale positive et significative avec des zones à haut risque de décès a été trouvée dans la région sud de l'Etat. CONCLUSIONS: La tendance de la mortalité liée à la maladie de Chagas dans l'état de Sergipe a augmenté au cours de la période analysée , avec une répartition hétérogène des cas. Une principale zone à risque a été identifiée dans la région sud de l'Etat.
Assuntos
Doença de Chagas/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Doença de Chagas/etiologia , Doença de Chagas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Análise Espaço-Temporal , Adulto JovemRESUMO
Neglected tropical diseases, such as Chagas disease caused by the protozoa Trypanosoma cruzi, affect millions of people worldwide but lack effective treatments that are accessible to the entire population, especially patients with the debilitating chronic phase. The recognition of host cells, invasion and its intracellular replicative success are essential stages for progression of the parasite life cycle and the development of Chagas disease. It is predicted that programmed cell death pathways (apoptosis) would be activated in infected cells, either via autocrine secretion or mediated by cytotoxic immune cells. This process should play a key role in resolving infections by hindering the evolutionary success of the parasite. In this research, we performed assays to investigate the role of the lectin galectin-3 (Gal3) in parasite-host signaling pathways. Using cells with endogenous levels of Gal3 compared to Gal3-deficient cells (induced by RNA interference), we demonstrated that T. cruzi mediated the survival pathways and the subverted apoptosis through Gal3 promoting a pro-survival state in infected cells. Infected Gal3-depleted cells showed increased activation of caspase 3 and pro-apoptotic targets, such as poly (ADP-ribose) polymerase (PARP), and lower accumulation of anti-apoptotic proteins, such as c-IAP1, survivin and XIAP. During the early stages of infection, Gal3 translocates from the cytoplasm to the nucleus and must act in survival pathways. In a murine model of experimental infection, Gal3 knockout macrophages showed lower infectivity and viability. In vivo infection revealed a lower parasitemia and longer survival and an increased spleen cellularity in Gal3 knockout mice with consequences on the percentage of T lymphocytes (CD4+ CD11b+) and macrophages. In addition, cytokines such as IL-2, IL-4, IL-6 and TNF-α are increased in Gal3 knockout mice when compared to wild type genotype. These data demonstrate a Gal3-mediated complex interplay in the host cell, keeping infected cells alive long enough for infection and intracellular proliferation of new parasites. However, a continuous knowledge of these signaling pathways should contribute to a better understanding the mechanisms of cell death subversion that are promoted by protozoans in the pathophysiology of neglected diseases such as Chagas disease.
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Apoptose/fisiologia , Doença de Chagas/parasitologia , Galectina 3/fisiologia , Trypanosoma cruzi/fisiologia , Análise de Variância , Animais , Western Blotting , Caspase 3/análise , Sobrevivência Celular , Doença de Chagas/mortalidade , Chlorocebus aethiops , Colorimetria , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Imunofluorescência , Galectina 3/análise , Galectina 3/genética , Células HeLa , Humanos , Imunofenotipagem , Macrófagos Peritoneais/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Parasitemia/mortalidade , Parasitemia/parasitologia , Fenótipo , Baço/patologia , Células VeroRESUMO
Chagas disease remains a major impediment to sustainable socioeconomic development in Latin America. Transplacental transmission explains the persistence of transmission in urban areas, in non-endemic regions, and in areas with an established interrupted vectorial transmission. One of every five cases of congenital Chagas disease in the world occurs in Colombia and Venezuela. The massive migration of impoverished populations from neighboring Venezuela has worsened the situation creating a humanitarian crisis in Northeastern Colombia, including the Sierra Nevada de Santa Marta. The prevalence of Chagas infection among pregnant women in these areas is higher than the national average, and the public health resources are insufficient. This perspective discusses the associated increased morbidity and mortality of congenital Chagas in this region, where stigmatization contributes to the impression among health authorities and the general population that it affects indigenous communities only. The monitoring and control of congenital Chagas disease in the Sierra Nevada of Santa Marta is a public health necessity that demands urgent and effective interventions.
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Doença de Chagas/congênito , Doença de Chagas/epidemiologia , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Doença de Chagas/mortalidade , Colômbia/epidemiologia , Feminino , Humanos , Gravidez , Saúde Pública , Trypanosoma cruziRESUMO
Autophagy is a catabolic pathway required for cellular and organism homeostasis. Autophagy participates in the innate and adaptive immune responses at different levels. Xenophagy is a class of selective autophagy that involves the elimination of intracellular pathogens. Trypanosoma cruzi is the causative agent of Chagas, a disease that affects 8 million individuals worldwide. Previously, our group has demonstrated that autophagy participates in the invasion of T. cruzi in non-phagocytic cells. In this work we have studied the involvement of autophagy in the development of T. cruzi infection in mice. Beclin-1 is a protein essential for autophagy, required for autophagosome biogenesis and maturation. We have performed an acute model of infection on the autophagic deficient Beclin-1 heterozygous knock-out mice (Bcln±) and compared to control Bcln+/+ animals. In addition, we have analyzed the infection process in both peritoneal cells and RAW macrophages. Our results have shown that the infection was more aggressive in the autophagy-deficient mice, which displayed higher numbers of parasitemia, heart´s parasitic nests and mortality rates. We have also found that peritoneal cells derived from Bcln± animals and RAW macrophages treated with autophagy inhibitors displayed higher levels of infection compared to controls. Interestingly, free cytosolic parasites recruited LC3 protein and other markers of xenophagy in control compared to autophagy-deficient cells. Taken together, these data suggest that autophagy plays a protective role against T. cruzi infection in mice, xenophagy being one of the processes activated as part of the repertoire of immune responses generated by the host.
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Autofagia , Doença de Chagas/imunologia , Interações Hospedeiro-Patógeno , Animais , Proteína Beclina-1/genética , Proteína Beclina-1/imunologia , Doença de Chagas/mortalidade , Modelos Animais de Doenças , Imunidade Inata , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células RAW 264.7 , Trypanosoma cruziRESUMO
Chagas disease continues to be an important cause of morbidity, mortality and disability in several Latin American countries, including Brazil. Using findings from the Global Burden of Disease Study 2016 (GBD, 2016), we present years of life lost, years lived with disability, and disability-adjusted life years due to Chagas disease in Brazil, by sex, age group, and Brazilian states, from 1990 to 2016. Results are reported in absolute numbers and age-standardized rates (per 100,000 population) with 95% uncertainty intervals. In 2016, 141,640 disability-adjusted life years (95% uncertainty intervals: 129,065-155,941) due to Chagas disease were estimated in Brazil, with a relative reduction of 36.7% compared with 1990 (223,879 disability-adjusted life years (95% uncertainty intervals: 209,372-238,591)). Age-standardized disability-adjusted life year rates declined at the national level (-69.7%) and in all Brazilian states between 1990 and 2016, but with different regional patterns. The decrease in the disability-adjusted life year rates was driven primarily by a consistent reduction in the years of life lost rates, the main component of total disability-adjusted life years for Chagas disease. The highest fatal and non-fatal burden due to Chagas disease was observed among males, the elderly, and in those Brazilian states encompassing important endemic areas for vector transmission in the past. Despite the consistent reduction in its burden during the period, Chagas disease is still an important and neglected cause of health lost due to premature mortality and disability in Brazil. Efforts should be made to maintain the political interest and sustainability of surveillance and control actions for Chagas disease, prevent the risk of re-emergence of vector transmission in endemic areas, and provide health care to chronically infected individuals, including early diagnosis and treatment interventions.
Assuntos
Doença de Chagas/epidemiologia , Efeitos Psicossociais da Doença , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Doença de Chagas/mortalidade , Doença de Chagas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Análise de Sobrevida , Adulto JovemRESUMO
Background: Neglected tropical diseases (NTDs) continue to be an important cause of disability and mortality in the poorest tropical and subtropical areas. Methods: This is an ecological study. We included all death certificates with dengue, cysticercosis and Chagas disease in Ecuador from 2011 to 2016. The spatial autocorrelation was evaluated by GeoDa software through the Global Moran's I index and the formation of clusters by the local index of spatial association. Results: The Global Moran's I index for the study period shows a positive spatial autocorrelation for dengue, cysticercosis and Chagas disease (0.25, p=0.001; 0.07, p=0.04; 0.45, p=0.001, respectively). Conclusions: The clusters identified as higher risk in the country could be targeted by policymakers to adequately develop strategies to strengthen health promotion policies that break the cycle of these diseases.
Assuntos
Doença de Chagas/mortalidade , Cisticercose/mortalidade , Dengue/mortalidade , Adulto , Idoso , Atestado de Óbito , Equador/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Negligenciadas/mortalidade , Pobreza , Características de Residência , Análise Espacial , Medicina TropicalRESUMO
BACKGROUND: The effectiveness of anti-parasite treatment with benznidazole in the chronic Chagas disease (ChD) remains uncertain. We evaluated, using data from the NIH-sponsored SaMi-Trop prospective cohort study, if previous treatment with benznidazole is associated with lower mortality, less advanced cardiac disease and lower parasitemia in patients with chronic ChD. METHODS: The study enrolled 1,959 ChD patients and abnormal electrocardiogram (ECG) from in 21 remote towns in Brazil. A total of 1,813 patients were evaluated at baseline and after two years of follow-up. Those who received at least one course of benznidazole were classified as treated group (TrG = 493) and those who were never treated as control group (CG = 1,320). The primary outcome was death after two-year follow-up; the secondary outcomes were presence at the baseline of major ChD-associated ECG abnormalities, NT-ProBNP levels suggestive of heart failure, and PCR positivity. RESULTS: Mortality after two years was 6.3%; it was lower in the TrG (2.8%) than the CG (7.6%); adjusted OR: 0.37 (95%CI: 0.21;0.63). The ECG abnormalities typical for ChD and high age-adjusted NT-ProBNP levels suggestive of heart failure were lower in the TrG than the CG, OR: 0.35 [CI: 0.23;0.53]. The TrG had significantly lower rates of PCR positivity, OR: 0.35 [CI: 0.27;0.45]. CONCLUSION: Patients previously treated with benznidazole had significantly reduced parasitemia, a lower prevalence of markers of severe cardiomyopathy, and lower mortality after two years of follow-up. If used in the early phases, benznidazole treatment may improve clinical and parasitological outcomes in patients with chronic ChD. TRIAL REGISTRATION: ClinicalTrials.gov, Trial registration: NCT02646943.
Assuntos
Doença de Chagas/tratamento farmacológico , Nitroimidazóis/administração & dosagem , Tripanossomicidas/administração & dosagem , Assistência ao Convalescente , Brasil/epidemiologia , Doença de Chagas/complicações , Doença de Chagas/mortalidade , Doença de Chagas/parasitologia , Doença Crônica/tratamento farmacológico , Seguimentos , Humanos , National Institutes of Health (U.S.) , Nitroimidazóis/efeitos adversos , Parasitemia/epidemiologia , Parasitemia/etiologia , Estudos Prospectivos , Trypanosoma cruzi/efeitos dos fármacos , Trypanosoma cruzi/fisiologia , Estados UnidosRESUMO
BACKGROUND: Chagas disease (CD) is a neglected chronic parasitic infection and a public health problem that is preventable, and has serious complications. In this study, the effects of age, period and birth cohort (APC Effects) on the evolution of the mortality of that disease in Brazil, from 1980-2014, according to sex and geographic region of the country, were analyzed. Mortality forecasts from the years 2015 to 2034 were estimated. METHODS: This is an ecological cross-sectional study in which death records and population data were extracted from the DATASUS (Department of Information Technology of the National Health System) website, in age groups from 20-24 years of age to 80 years and over, from 1980 to 2014. The rates were standardized according to age and sex distributions using the direct method. The APC models were estimated using the Bayesian approach, and the INLA (Integrated Nested Laplace Approximations) method was used for parameter inference. Super dispersion of the data was considered, and we included unstructured random terms in the models. RESULTS: During the analyzed period, there were 178,823 deaths in Brazil (3.85 annual deaths per 100,000 inhabitants). It was found that temporal effects on CD mortality varied by sex and region. In general, there was an increase in mortality rates up to 30 years of age, and the mortality rates were higher between 50 and 64 years of age. On average, men died five years younger than women. Mortality rates were highest in the Central West and Southeast regions. The Central West, Southeast and Southern regions had a reduction over time in the rate of CD deaths between 2000 and 2014. The mortality rate in the Northeast was not statistically different in any period analyzed, while the North had tendency to increase; however, a significant risk increase was only observed between 1995 and 1999. The rate of mortality was high in older birth cohorts. The overall prediction for the next two decades showed a progressive decline in CD mortality, which will be highest among the young. The expected average reduction was 76.1% compared to the last observed period (2010-2014) and the last predicted (2030-2034) period. The average reduction ranged from 86% in the 20-24 age group to 50% in the 80 and over age group. CONCLUSIONS: In the present study, a higher death rate was observed for ages above 30 years, especially 50 to 64 years, and in the older birth cohorts. We believe these results can be related to period effects of vector control actions and preventive and care measures by the health system of Brazil, in addition to demographic changes in the period. The differences among the regions reflect socioeconomic inequities and access to the healthcare systems in the Brazilian population.
Assuntos
Doença de Chagas/mortalidade , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , Brasil/epidemiologia , Efeito de Coortes , Estudos Transversais , Feminino , Geografia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Análise de Sobrevida , Adulto JovemRESUMO
During the acute phase of Trypanosoma cruzi infection, macrophages can act as host cells for the parasites as well as effector cells in the early anti-parasitic immune response. Thus, the targeting of specific signaling pathways could modulate macrophages response to restrict parasite replication and instruct an appropriate adaptive response. Recently, it has become evident that Wnt signaling has immunomodulatory functions during inflammation and infection. Here, we tested the hypothesis that during T. cruzi infection, the activation of Wnt signaling pathway in macrophages plays a role in modulating the inflammatory/tolerogenic response and therefore regulating the control of parasite replication. In this report, we show that early after T. cruzi infection of bone marrow-derived macrophages (BMM), ß-catenin was activated and Wnt3a, Wnt5a, and some Frizzled receptors as well as Wnt/ß-catenin pathway's target genes were upregulated, with Wnt proteins signaling sustaining the activation of Wnt/ß-catenin pathway and then activating the Wnt/Ca+2 pathway. Wnt signaling pathway activation was critical to sustain the parasite's replication in BMM; since the treatments with specific inhibitors of ß-catenin transcriptional activation or Wnt proteins secretion limited the parasite replication. Mechanistically, inhibition of Wnt signaling pathway armed BMM to fight against T. cruzi by inducing the production of pro-inflammatory cytokines and indoleamine 2,3-dioxygenase activity and by downregulating arginase activity. Likewise, in vivo pharmacological inhibition of the Wnts' interaction with its receptors controlled the parasite replication and improved the survival of lethally infected mice. It is well established that T. cruzi infection activates a plethora of signaling pathways that ultimately regulate immune mediators to determine the modulation of a defined set of effector functions in macrophages. In this study, we have revealed a new signaling pathway that is activated by the interaction between protozoan parasites and host innate immunity, establishing a new conceptual framework for the development of new therapies.
Assuntos
Doença de Chagas/imunologia , Interações Hospedeiro-Parasita/imunologia , Macrófagos/imunologia , Trypanosoma cruzi/imunologia , Via de Sinalização Wnt/imunologia , Animais , Linhagem Celular , Doença de Chagas/tratamento farmacológico , Doença de Chagas/mortalidade , Doença de Chagas/parasitologia , Modelos Animais de Doenças , Humanos , Macrófagos/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
BACKGROUND: Chagas disease is related to ischemic stroke (IS), although few epidemiological studies have evaluated the associated mortality and recurrence. Our objective is to determine factors associated with mortality and recurrence of IS in patients with IS and Chagas disease. METHODS: We retrospectively studied data obtained from electronic medical records of patients admitted at SARAH Hospitals across Brazil between 2009 and 2013. Using Cox regression analysis for mortality and logistic regression for recurrence, we assessed primary population characteristics and statistical associations between risk factors and outcomes. RESULTS: We analyzed 279 patients who were followed up until 2016. The mean age at stroke onset was 61 with a 10% frequency of death. Multivariate analysis assessing mortality demonstrated that the associated factors were age at stroke (hazard ratio [HR] 1.04), initial modified Rankin Scale (mRS; HR 20.91), bladder dysfunction (HR 2.51), diabetes mellitus (DM; HR 3.64), and alcoholism (HR 3.37). Multivariate analysis assessing recurrence demonstrated that the associated factors were age at ictus (OR 0.96), cognitive deficit (OR 0.44), initial mRS (OR 1.84), cardioembolic etiology (OR 2.47), and female sex (OR 2.73). CONCLUSIONS: Cardiac conditions did not correlate with mortality or recurrence. Age was a protective factor against recurrence, probably due to cumulative risk of IS over time, while initial mRS was associated with both outcomes. Treating diseases such as DM and bladder dysfunction, and early treatment to reduce the initial mRS could potentially prevent both outcomes; also, establishing a correct etiological diagnosis is important.
Assuntos
Doença de Chagas/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Idoso , Brasil/epidemiologia , Infarto Cerebral/complicações , Infarto Cerebral/epidemiologia , Doença de Chagas/mortalidade , Estudos de Coortes , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Fatores de RiscoRESUMO
A cardiomiopatia crônica da doença de Chagas (CCDC) é resultante de miocardite fibrosante focal de baixa intensidade, mas incessante, causada pela infecção persistente do T cruzi, associada à inflamação mediada por mecanismos imunes adversos. Cerca de 30% dos infectados desenvolvem, ao longo da vida, a forma crônica cardíaca da doença de Chagas com manifestação clínica proteiforme, que pode incluir morte súbita, sintomas e sinais de insuficiência cardíaca, eventos cardioembólicos, arritmia e sintomas anginoides. A morte súbita e a progressão da insuficiência cardíaca (IC) são os mecanismos mais comuns de óbito nesta condição. Os aspectos prognósticos mais relevantes são sintomas de IC avançada (CF III/IV da NYHA), cardiomegalia, disfunção sistólica do VE e taquicardia ventricular não sustentada. A prevenção dos eventos cardioembólicos é aspecto importante no manejo dos pacientes com CCDC. Agentes anticoagulantes orais devem ser indicados para pacientes com risco elevado, conforme a presença de um conjunto de fatores de risco: disfunção sistólica do VE, aneurisma apical, alteração da repolarização ventricular ao ECG e idade avançada. O tratamento da IC na CCDC segue os mesmos princípios aplicados à IC secundária à cardiomiopatia dilatada de outras etiologias
Assuntos
Humanos , Masculino , Feminino , Cardiomiopatias/mortalidade , Cardiomiopatia Chagásica/mortalidade , Doença de Chagas/epidemiologia , Doença de Chagas/mortalidade , Morte Súbita , Ecocardiografia/métodos , Eletrocardiografia Ambulatorial/métodos , Eletrocardiografia/métodos , Espectroscopia de Ressonância Magnética/métodos , Valva Mitral , Valva Tricúspide , Trypanosoma cruzi/parasitologiaRESUMO
Chagas disease is a potentially fatal disease caused by the parasite Trypanosoma cruzi, which can in some cases affect the central nervous system. The objective was to evaluate the effect of aspirin (ASA) in the behavior of mice infected with T. cruzi during the acute phase. This was an experimental study with random assignation. Twenty four BALB/c mice were divided into four groups of six animals each as follows: only ASA (OA), ASA before infection (BI), ASA after infection (AI) and only infection (OI). The strain used for infection was M/HOM/Bra/53/Y. An ASA dose of 100 mg/kg per day was administered 72 h before infection to BI group and the same dose 48 h after infection to AI group. Mice behavior in the open field test, mortality, and brain histopathology was evaluated. Data were analyzed using ANOVA, chi square test, and Kaplan-Meier with long-rank for survival analysis. In the open field test, the OA group has similar results with the BI group, in the variables of immobility and escape. Also, the OA group displayed significantly higher rates of micturition (p < 0.001) and defecation (p < 0.001) compared to infected groups. Mortality was higher in BI group (p = 0.02). The presence of T. cruzi amastigotes were higher in brain tissues of the AI and OI groups (p = 0.008). In conclusion, the administration of ASA before infection seemed to prevent behavioral changes induced by the acute infection, but it led to accelerated mortality. The study highlighted the potential importance of the pathways inhibited by ASA in the early hours of acute infection with T. cruzi.