RESUMEN
By controlling the transmission of Chagas disease, the challenge of providing assistance to millions of infected patients that reach old age arises. In this study, the socioeconomic, demographic and comorbidity records of all elderly chagasic patients followed at the Pharmaceutical Care Service of the Chagas Disease Research Laboratory were assessed. The information related to the clinical form of the disease was obtained from medical records provided by the Walter Cantídio University Hospital. The profile of the studied population was: women (50.5%); mean age of 67 years; retired (54.6%); married (51.6 %); high illiteracy rate (40.2%); and family income equal to the minimum wage (51.5%). The predominant clinical forms of Chagas disease were cardiac (65.3%) and indeterminate (14.7%). The main electrocardiographic changes were the right bundle branch block (41.0%), associated or not with the anterosuperior left bundle branch block (27.4%). The average number of comorbidities per patient was 2.23 ± 1.54, with systemic arterial hypertension being the main one found (67.0%). It was found that the elderly comprise a vulnerable group of patients that associate aging with cardiac and/or digestive disorders resulting from the evolution of Chagas disease and other comorbidities, which requires special attention from health services to ensure more appropriate medical and social care.
Asunto(s)
Enfermedad de Chagas/epidemiología , Servicios Farmacéuticos , Anciano , Brasil/epidemiología , Enfermedad Crónica , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores SocioeconómicosRESUMEN
By controlling the transmission of Chagas disease, the challenge of providing assistance to millions of infected patients that reach old age arises. In this study, the socioeconomic, demographic and comorbidity records of all elderly chagasic patients followed at the Pharmaceutical Care Service of the Chagas Disease Research Laboratory were assessed. The information related to the clinical form of the disease was obtained from medical records provided by the Walter Cantídio University Hospital. The profile of the studied population was: women (50.5%); mean age of 67 years; retired (54.6%); married (51.6 %); high illiteracy rate (40.2%); and family income equal to the minimum wage (51.5%). The predominant clinical forms of Chagas disease were cardiac (65.3%) and indeterminate (14.7%). The main electrocardiographic changes were the right bundle branch block (41.0%), associated or not with the anterosuperior left bundle branch block (27.4%). The average number of comorbidities per patient was 2.23 ± 1.54, with systemic arterial hypertension being the main one found (67.0%). It was found that the elderly comprise a vulnerable group of patients that associate aging with cardiac and/or digestive disorders resulting from the evolution of Chagas disease and other comorbidities, which requires special attention from health services to ensure more appropriate medical and social care.
Controlando-se a transmissão da doença de Chagas, surge o desafio de prestar assistência a milhões de pacientes infectados que chegam à velhice. Neste estudo, foram avaliados os registros socioeconômicos, demográficos e de comorbidades de todos os pacientes chagásicos idosos acompanhados no Serviço de Atenção Farmacêutica do Laboratório de Pesquisa em Doença de Chagas. As informações relacionadas à forma clínica da doença foram obtidas a partir de registros médicos disponibilizados pelo Hospital Universitário Walter Cantídio. O perfil da população estudada foi de: mulheres (50,5%); idade média de 67 anos; aposentados (54,6%); casados (51,6%); alta taxa de analfabetismo (40,2%); e renda familiar de um salário mínimo (51,5%). As formas clínicas predominantes da doença de Chagas foram a cardíaca (65,3%) e a indeterminada (14,7%). As principais alterações eletrocardiográficas foram o bloqueio de ramo direito (41,0%), associado ou não ao bloqueio ântero superior esquerdo (27,4%). O número médio de comorbidades por paciente foi de 2,23 ± 1,54, sendo a hipertensão arterial sistêmica a principal encontrada (67,0%). Verificou-se que os idosos constituem grupo vulnerável de pacientes que associam o envelhecimento com as alterações cardíacas e/ou digestivas resultantes da evolução da doença de Chagas e outras comorbidades, o que exige atenção especial dos serviços de saúde para um atendimento médico e social mais adequado.
Asunto(s)
Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Chagas/epidemiología , Servicios Farmacéuticos , Brasil/epidemiología , Enfermedad Crónica , Estudios Transversales , Factores SocioeconómicosRESUMEN
In Chagas disease, understanding how the immune response controls parasite growth but also leads to heart damage may provide insight into the design of new therapeutic strategies. Tumor necrosis factor-alpha (TNF-alpha) is important for resistance to acute Trypanosoma cruzi infection; however, in patients suffering from chronic T. cruzi infection, plasma TNF-alpha levels correlate with cardiomyopathy. Recent data suggest that CD8-enriched chagasic myocarditis formation involves CCR1/CCR5-mediated cell migration. Herein, the contribution of TNF-alpha, especially signaling through the receptor TNFR1/p55, to the pathophysiology of T. cruzi infection was evaluated with a focus on the development of myocarditis and heart dysfunction. Colombian strain-infected C57BL/6 mice had increased frequencies of TNFR1/p55+ and TNF-alpha+ splenocytes. Although TNFR1-/- mice exhibited reduced myocarditis in the absence of parasite burden, they succumbed to acute infection. Similar to C57BL/6 mice, Benznidazole-treated TNFR1-/- mice survived acute infection. In TNFR1-/- mice, reduced CD8-enriched myocarditis was associated with defective activation of CD44+CD62Llow/- and CCR5+ CD8+ lymphocytes. Also, anti-TNF-alpha treatment reduced the frequency of CD8+CCR5+ circulating cells and myocarditis, though parasite load was unaltered in infected C3H/HeJ mice. TNFR1-/- and anti-TNF-alpha-treated infected mice showed regular expression of connexin-43 and reduced fibronectin deposition, respectively. Furthermore, anti-TNF-alpha treatment resulted in lower levels of CK-MB, a cardiomyocyte lesion marker. Our results suggest that TNF/TNFR1 signaling promotes CD8-enriched myocarditis formation and heart tissue damage, implicating the TNF/TNFR1 signaling pathway as a potential therapeutic target for control of T. cruzi-elicited cardiomyopathy.
Asunto(s)
Antiinflamatorios/farmacología , Anticuerpos Monoclonales/farmacología , Linfocitos T CD8-positivos/inmunología , Cardiomiopatía Chagásica/inmunología , Receptores CCR5/inmunología , Receptores Tipo I de Factores de Necrosis Tumoral/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Animales , Movimiento Celular , Cardiomiopatía Chagásica/tratamiento farmacológico , Enfermedad Crónica , Femenino , Citometría de Flujo , Inmunohistoquímica , Infliximab , Ratones , Ratones Endogámicos C57BL , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Receptores Tipo I de Factores de Necrosis Tumoral/sangre , Receptores Tipo I de Factores de Necrosis Tumoral/inmunología , Transducción de Señal , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
In Chagas disease, understanding how the immune response controls parasite growth but also leads to heart damage may provide insight into the design of new therapeutic strategies. Tumor necrosis factor-alpha (TNF-á) is important for resistance to acute Trypanosoma cruzi infection; however, in patients suffering from chronic T. cruzi infection, plasma TNF-á levels correlate with cardiomyopathy. Recent data suggest that CD8-enriched chagasic myocarditis formation involves CCR1/CCR5-mediated cell migration. Herein, the contribution of TNF-á, especially signaling through the receptor TNFR1/p55, to the pathophysiology of T. cruzi infection was evaluated with a focus on the development of myocarditis and heart dysfunction. Colombian strain-infected C57BL/6 mice had increased frequencies of TNFR1/p55+ and TNF-á+ splenocytes. Although TNFR1-/- mice exhibited reduced myocarditis in the absence of parasite burden, they succumbed to acute infection. Similar to C57BL/6 mice, Benznidazole-treated TNFR1-/- mice survived acute infection. In TNFR1-/- mice, reduced CD8-enriched myocarditis was associated with defective activation of CD44+CD62Llow/- and CCR5+ CD8+ lymphocytes. Also, anti-TNF-á treatment reduced the frequency of CD8+CCR5+ circulating cells and myocarditis, though parasite load was unaltered in infected C3H/HeJ mice. TNFR1-/- and anti-TNF-á-treated infected mice showed regular expression of connexin-43 and reduced fibronectin deposition, respectively. Furthermore, anti-TNF-á treatment resulted in lower levels of CK-MB, a cardiomyocyte lesion marker. Our results suggest that TNF/TNFR1 signaling promotes CD8-enriched myocarditis formation and heart tissue damage, implicating the TNF/TNFR1 signaling pathway as a potential therapeutic target for control of T. cruzi-elicited cardiomyopathy.
Asunto(s)
Animales , Femenino , Ratones , Antiinflamatorios/farmacología , Anticuerpos Monoclonales/farmacología , /inmunología , Cardiomiopatía Chagásica/inmunología , /inmunología , Receptores Tipo I de Factores de Necrosis Tumoral/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Movimiento Celular , Enfermedad Crónica , Cardiomiopatía Chagásica/tratamiento farmacológico , Citometría de Flujo , Inmunohistoquímica , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Receptores Tipo I de Factores de Necrosis Tumoral/sangre , Receptores Tipo I de Factores de Necrosis Tumoral/inmunología , Transducción de Señal , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
In this study, we investigated the involvement of Th1 cytokines in the expression of cell adhesion molecules (CAM) and recruitment of inflammatory cells to the heart of mice infected with Trypanosoma cruzi. Our results show that endogenously produced IFN-gamma is essential to induce optimal expression of VCAM-1 and ICAM-1 on the cardiac vascular endothelium of infected mice. Furthermore, the influx of inflammatory cells into the cardiac tissue was impaired in Th1 cytokine-deficient infected mice, paralleling the intensity of VCAM-1 and ICAM-1 expression on the vascular endothelium. Consistent with the importance of ICAM-1 in host resistance, ICAM-1 knockout (KO) mice were highly susceptible to T. cruzi infection, as assessed by mortality rate, parasitemia, and heart tissue parasitism. The enhanced parasitism was associated with a decrease in the numbers of CD4(+) and CD8(+) T lymphocytes in the heart tissue of ICAM-1 KO mice. Additionally, ICAM-1 KO mice mounted an unimpaired IFN-gamma response and IFN-gamma-dependent production of reactive nitrogen intermediates and parasite- specific IgG2a. Supporting the participation of ICAM-1 in cell migration during T. cruzi infection, the entrance of adoptively transferred PBL from T. cruzi-infected wild-type C57BL/6 mice into the cardiac tissue of ICAM-1 KO mice was significantly abrogated. Therefore, we favor the hypothesis that ICAM-1 plays a crucial role in T lymphocyte recruitment to the cardiac tissue and host susceptibility during T. cruzi infection.
Asunto(s)
Enfermedad de Chagas/inmunología , Molécula 1 de Adhesión Intercelular/fisiología , Linfocitos T/fisiología , Animales , Movimiento Celular , Susceptibilidad a Enfermedades , Femenino , Molécula 1 de Adhesión Intercelular/análisis , Interferón gamma/fisiología , Interleucina-12/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Miocardio/inmunología , Molécula 1 de Adhesión Celular Vascular/análisisRESUMEN
Sera and peripheral blood mononuclear cells (PBMC) from patients displaying different clinical symptoms as well as from normal uninfected individuals (NI) were used to evaluate the humoral and cellular responses of Chagas' disease patients to Trypanosoma cruzi-derived paraflagellar rod proteins (PFR). Our results show that sera from both asymptomatic Chagas' disease patients (ACP) and cardiac Chagas' disease patients (CCP) have higher levels of antibodies to PFR than sera from NI. Immunoglobulin G1 (IgG1) and IgG3 were the main Ig isotypes that recognized PFR. We also tested three recombinant forms of PFR, named rPAR-1, rPAR-2, and rPAR-3, by Western blot analysis. Sera from seven out of eight patients with Chagas' disease recognized one of the three rPAR forms. Sera from 75, 50, and 37.5% of Chagas' disease patients tested recognized rPAR-3, rPAR-2, and rPAR-1, respectively. PFR induced proliferation of 100 and 70% of PBMC from ACP and CCP, respectively. Further, stimulation of cells from Chagas' disease patients with PFR enhanced the frequencies of both small and large CD4(+) CD25(+) and CD4(+) CD69(+) lymphocytes, as well as that of small CD8(+) CD25(+) lymphocytes. Finally, we evaluated the ability of PFR to elicit the production of gamma interferon (IFN-gamma) by PBMC from patients with Chagas' disease. Fifty percent of the PBMC from ACP as well as CCP produced IFN-gamma upon stimulation with PFR. PFR enhanced the percentages of IFN-gamma-producing cells in both CD3(+) and CD3(-) populations. Within the T-cell population, large CD4(+) T lymphocytes were the main source of IFN-gamma.