RESUMEN
Neglected tropical diseases are a diverse group of communicable pathologies that mainly prevail in tropical and subtropical regions. Thus, the objective of this work was to evaluate the biological potential of eight 4-(4-chlorophenyl)thiazole compounds. Tests were carried out in silico to evaluate the pharmacokinetic properties, the antioxidant, cytotoxic activities in animal cells and antiparasitic activities were evaluated against the different forms of Leishmania amazonensis and Trypanosoma cruzi in vitro. The in silico study showed that the evaluated compounds showed good oral availability. In a preliminary in vitro study, the compounds showed moderate to low antioxidant activity. Cytotoxicity assays show that the compounds showed moderate to low toxicity. In relation to leishmanicidal activity, the compounds presented IC50 values that ranged from 19.86 to 200 µM for the promastigote form, while for the amastigote forms, IC50 ranged from 101 to more than 200 µM. The compounds showed better results against the forms of T. cruzi with IC50 ranging from 1.67 to 100 µM for the trypomastigote form and 1.96 to values greater than 200 µM for the amastigote form. This study showed that thiazole compounds can be used as future antiparasitic agents.
Asunto(s)
Enfermedad de Chagas , Leishmania mexicana , Tripanocidas , Trypanosoma cruzi , Animales , Tripanocidas/farmacología , Enfermedad de Chagas/tratamiento farmacológico , Antiparasitarios/farmacologíaRESUMEN
Visceral Leishmaniasis (VL) is a severe parasitic disease that has emerged as an important opportunistic condition in HIV-infected patients and whose control is impaired by inaccurate identification. This is mainly due to the serological tests used for VL having a reduced performance in cases of VL-HIV coinfection due to a low humoral response. In this situation, however, a positive test has even greater diagnostic value when combined with the clinical status. This study aimed to evaluate the application and performance of flow cytometry to detect anti-Leishmania infantum antibodies in HIV-infected patients. Sera from VL/HIV coinfected patients, characterized using "gold standard" techniques, were compared with sera from healthy controls plus sera from HIV-infected individuals. The flow cytometry results were expressed as levels of IgG reactivity, based on the percentage of positive fluorescent parasites (PPFP). A ROC curve analysis of a serum titration indicated a PPFP of 1.26% as being the cutoff point to segregate positive and negative results. At the 1:2,048 dilution, with 89% sensitivity and 83% specificity, flow cytometry showed greater sensitivity in relation to the serological tests evaluated. Futhermore, flow cytometry was the only assay that positively identified all VL-HIV patients with quantified HIV load. Together, these findings suggest that flow cytometry may be used as an alternative serological approach for VL identification and as a tool to characterize the humoral response against Leishmania infantum in HIV-infected patients.
RESUMEN
We report a case of visceral leishmaniasis (VL)/HIV coinfection in a patient undergoing regular antiretroviral therapy and treatment with thalidomide for erythema nodosum leprosum. He presented at a health service with high fever, chills, asthenia, pale skin, lower limb edema, hepatomegaly, and splenomegaly. Visceral leishmaniasis was confirmed by direct examination, and serological and molecular tests. Serum levels of Th1/Th2 cytokines were measured. The patient began treatment with liposomal amphotericin B, with good clinical response; however, VL recurred 6 months later. Treatment was reinitiated, maintaining secondary prophylaxis with liposomal amphotericin B. The patient showed clinical improvement with important recovery of CD4+ T-lymphocyte count.
Asunto(s)
Anfotericina B/uso terapéutico , Antirretrovirales/uso terapéutico , Eritema Nudoso/tratamiento farmacológico , Infecciones por VIH/complicaciones , Leishmaniasis Visceral/diagnóstico , Adulto , Coinfección , Eritema Nudoso/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Humanos , Leishmaniasis Visceral/complicaciones , Leishmaniasis Visceral/tratamiento farmacológico , Masculino , Recurrencia , Resultado del TratamientoRESUMEN
While the role of cytokine genes has been well documented in the context of Leishmania (Viannia) braziliensis infection, no studies have addressed the influence of human leukocyte antigen-G (HLA-G) in susceptibility/resistance to American Tegumentary Leishmaniasis (ATL). Here, we evaluated the influences of HLA-G, IL-10, TNF-A and IFN-G in the susceptibility and clinical manifestations of ATL. DNA of 114 ATL patients and 346 healthy individuals were sequenced for well-documented polymorphisms in HLA-G 3' untranslated region (UTR), in IL-10 and TNF-A promoters and in IFN-G intron 1. Soluble HLA-G (sHLA-G) and cytokine levels were evaluated by ELISA and flow cytometry, respectively. Analyses were performed using GraphPad and R-package software. Individuals bearing HLA-G +3142G/G showed an association with increased risk for ATL, whereas those carrying the HLA-G +3142C/G and one copy of UTR6 haplotype, showed an association with decreased risk for ATL. sHLA-G was overexpressed in "susceptible" patients compared to the "resistant'' one, and also in patients bearing +3142G/G genotype. From these results, HLA-G +3142G/G may be considered as genotype of susceptibility and UTR6 as marker of protection to ATL. Our findings showed a participation of HLA-G in the pathogenesis of the ATL.
Asunto(s)
Región de Flanqueo 3'/genética , Genotipo , Antígenos HLA-G/genética , Leishmaniasis/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil , Niño , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
BACKGROUND: Thiazolidine-2,4-dione ring system is used as a pharmacophore to build various heterocyclic compounds aimed to interact with biological targets. In the present study, benzylidene-2,4-thiazolidinedione derivatives (compounds 2-5) were synthesized and screened against cancer cell lines and the genotoxicity and cytotoxicity of the most active compound (5) was investigated on normal and lung cancer cell line. METHODS: For in vitro cytotoxic screening, the MTT assay was used for HL60 and K562 (leukemia), MCF-7 (breast adenocarcinoma), HT29 (colon adenocarcinoma), HEp-2 (cervix carcinoma) and NCI-H292 (lung carcinoma) tumor cell lines and Alamar-blue assay was used for non-tumor cells (PBMC, human peripheral blood mononuclear cells) were used. Cell morphology was visualized after Giemsa-May-Grunwald staining. DNA content, phosphatidylserine externalization and mitochondrial depolarization were measured by flow cytometry. Genotoxicity was assessed by Comet assay. RESULTS: 5-(2-Bromo-5-methoxybenzylidene)-thiazolidine-2,4-dione (5) presented the most potent cytotoxicity, especially against NCI-H292 lung cancer cell line, with IC50 value of 1.26µg/mL after 72h incubation. None of the compounds were cytotoxic to PBMC. After 48h incubation, externalization of phosphatidylserine, mitochondrial depolarization, internucleosomal DNA fragmentation and morphological alterations consistent with apoptosis were observed in NCI-H292 cells treated with compound (5). In addition, compound (5) also induced genotoxicity in NCI-H292 cells (2.8-fold increase in damage index compared to the negative control), but not in PBMC. CONCLUSION: Compound 5 presented selective cytotoxic and genotoxic activity against pulmonary carcinoma (NCI-H292 cells).
Asunto(s)
Antineoplásicos/farmacología , Citotoxinas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Mutágenos/farmacología , Tiazolidinedionas/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Ensayo Cometa/métodos , Fragmentación del ADN/efectos de los fármacos , Células HL-60 , Humanos , Células K562 , Leucocitos Mononucleares/efectos de los fármacos , Células MCF-7RESUMEN
Complexes [Sb(QN)(2)Cl] (1), [Sb(QC)(2)Cl] (2) and [Sb(QI)(2)Cl] (3) were obtained with 8-hydroxyquinoline (HQN), 5-chloro-8-hydroxyquinoline (HQC) and 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol, HQI). The quinoline derivatives and their antimony(III) complexes were evaluated for their anti-trypanosomal activity as well as for their cytotoxicity against HL-60 and Jurkat human leukemia cell lines. Upon coordination to antimony(III) the anti-trypanosomal activity of HQC and HQI increases, the highest improvement being observed for complex (3), which was the most active among all studied compounds against both epimastigote and trypomastigote forms of Trypanosoma cruzi. All quinoline derivatives proved to be cytotoxic against both leukemia cell lineages. Upon coordination to antimony(III) the cytotoxicity of HQN improved against Jurkat leukemia cells. While SbCl(3) proved to be cytotoxic against HL-60 cells, it was not active against Jurkat cells. However, its coordination to the quinoline derivatives resulted in complexes with significant cytotoxicity against Jurkat cells.
Asunto(s)
Antimonio/química , Antineoplásicos/farmacología , Antiprotozoarios/farmacología , Hidroxiquinolinas/química , Compuestos Organometálicos/farmacología , Trypanosoma cruzi/efectos de los fármacos , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Antiprotozoarios/síntesis química , Antiprotozoarios/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células HL-60 , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Pruebas de Sensibilidad Parasitaria , Bazo/citología , Bazo/efectos de los fármacos , Relación Estructura-Actividad , Trypanosoma cruzi/crecimiento & desarrolloRESUMEN
In this study, we have the objective of evaluating the lymphoproliferative response and determining interferon (IFN)-gamma and interleukin (IL)-10 cytokine production in the peripheral blood mononuclear cells (PBMC) of patients with American tegumentary leishmaniasis prior and post 12 months of chemotherapy treatment with meglumine antimoniate compared with the PBMC of noninfected donors. Lymphoproliferation, such as cytokine production, was evaluated through in vitro stimulus with the soluble antigenic fraction from Leishmania (Viannia) braziliensis promastigotes (1.25 microg/ml) and Concanavalin A (2.5 microg/ml). Patients showed a significant lymphoproliferative response prior and post treatment compared with the control group. Similar result, prior to chemotherapy treatment, was observed in IFN-gamma and IL-10 production when patients were compared with the control group. After chemotherapy treatment, PBMC lymphoproliferative response of the patients revealed an increase, whereas patients have shown a decrease in IFN-gamma levels and an increase in IL-10, although without statistical difference. These results may indicate that the patients produced a specific cellular response to the soluble antigenic fraction suggesting that besides Th1 and Th2 dichotomy, immunological regulation mechanisms with the participation of memory T cells and regulatory T cells could be present in the clinical evolution of these patients. This understanding will allow the study and identification of new L. (V.) braziliensis molecules potentially candidates to vaccines.
Asunto(s)
Inmunidad Celular/fisiología , Interferón gamma/inmunología , Interleucina-10/inmunología , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/inmunología , Animales , Antígenos de Protozoos/inmunología , Estudios de Casos y Controles , Concanavalina A/farmacología , Femenino , Estudios de Seguimiento , Humanos , Interferón gamma/análisis , Interleucina-10/análisis , Leishmania braziliensis/inmunología , Leishmaniasis Cutánea/parasitología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Masculino , Meglumina/uso terapéutico , Antimoniato de Meglumina , Compuestos Organometálicos/uso terapéutico , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
We propose to analyze the relation between the cellular immune response of Chagas' disease patients after in vitro stimulation of peripheral blood mononuclear cells (PBMC) with recombinant antigens cytoplasmatic repetitive antigen (CRA) or flagellar repetitive antigen (FRA) of T. cruzi and the chronic clinical forms of disease. Cells were stimulated using phytohemagglutinin, CRA, FRA, or a soluble antigen of Epimastigota (Ag-Epi) for 24 hr, 72 hr, or 6 days. The proliferation of cells was evaluated after 6 days of culture by quantification of incorporated 3H-thymidine. Cytokines were measured in the supernatants obtained after 24 hr (tumor necrosis factor [TNF]-alpha and interleukin [IL]-4), 72 hr (IL-10), and 6 days (interferon [IFN]-gamma) using enzyme-linked immunosorbent assay (ELISA). Cells of the Chagas patients stimulated with the recombinant antigens exhibited higher proliferation responses compared with that of non-Chagas (NC) individuals. However, when proliferation was compared between patients with the cardiac form (CF) or indeterminate form (IF), it was not possible to establish a difference in the response. So far as the cytokines secreted in the culture supernatants after stimulation in vitro with T. cruzi antigens were concerned, the results showed that CRA, as well as Epi-Ag, were able to stimulate the production of TNF-alpha and IFN-gamma in Chagas patients as compared with NC individuals. However, the cytokine levels after stimulation with the T. cruzi antigens were not different between the patients with CF and IF. CRA was capable of inducing a T helper type 1 (Th1) immune response, with elevated production of TNF-alpha and IFN-gamma in Chagas patients that are carriers of CF and IF clinical forms.
Asunto(s)
Antígenos de Protozoos/inmunología , Enfermedad de Chagas/inmunología , Enfermedad de Chagas/parasitología , Inmunidad Celular/inmunología , Proteínas Recombinantes/inmunología , Trypanosoma cruzi/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Portador Sano/parasitología , Células Cultivadas , Femenino , Humanos , Inmunidad Celular/efectos de los fármacos , Interferón gamma/inmunología , Interleucina-10/inmunología , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Linfocitos/parasitología , Masculino , Persona de Mediana Edad , Mitógenos/farmacología , Fracciones Subcelulares/efectos de los fármacos , Fracciones Subcelulares/parasitología , Trypanosoma cruzi/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Protamine sulphate/DNA complexes have been shown to protect DNA from DNase digestion in a lipid system for gene transfer. A DNA-based vaccine complexed to protamine sulphate was used to induce an immune response against Schistosoma mansoni anchored-glycosylphosphatidylinositol tegumental antigen in BALB/c mice. The protection elicited ranged from 33 to 44%. The spectrum of the elicited immune response induced by the vaccine formulation without protamine was characterized by a high level of IgG (IgG1> IgG2a). Protamine sulphate added to the DNA vaccine formulation retained the green fluorescent protein encoding-plasmid longer in muscle and spleen. The experiments in vivo showed that under protamine sulphate effect, the scope of protection remained unchanged, but a modulation in antibody production (IgG1= IgG2a) was observed.
Asunto(s)
Anticuerpos Antihelmínticos/inmunología , Antígenos Helmínticos/inmunología , Glicosilfosfatidilinositoles/inmunología , Antagonistas de Heparina/inmunología , Protaminas/inmunología , Schistosoma mansoni/inmunología , Vacunas de ADN/inmunología , Animales , Anticuerpos Antihelmínticos/sangre , Antígenos Helmínticos/administración & dosificación , Femenino , Glicosilfosfatidilinositoles/administración & dosificación , Antagonistas de Heparina/administración & dosificación , Inmunoglobulina G/inmunología , Ratones , Ratones Endogámicos BALB C , Protaminas/administración & dosificación , Esquistosomiasis mansoni/prevención & control , Factores de Tiempo , Vacunas de ADN/administración & dosificaciónRESUMEN
Protamine sulphate/DNA complexes have been shown to protect DNA from DNase digestion in a lipid system for gene transfer. A DNA-based vaccine complexed to protamine sulphate was used to induce an immune response against Schistosoma mansoni anchored-glycosylphosphatidylinositol tegumental antigen in BALB/c mice. The protection elicited ranged from 33 to 44 percent. The spectrum of the elicited immune response induced by the vaccine formulation without protamine was characterized by a high level of IgG (IgG1> IgG2a). Protamine sulphate added to the DNA vaccine formulation retained the green fluorescent protein encoding-plasmid longer in muscle and spleen. The experiments in vivo showed that under protamine sulphate effect, the scope of protection remained unchanged, but a modulation in antibody production (IgG1= IgG2a) was observed.
Asunto(s)
Animales , Femenino , Ratones , Anticuerpos Antihelmínticos/inmunología , Antígenos Helmínticos/inmunología , Glicosilfosfatidilinositoles/inmunología , Antagonistas de Heparina/inmunología , Protaminas/inmunología , Schistosoma mansoni/inmunología , Vacunas de ADN/inmunología , Anticuerpos Antihelmínticos/sangre , Antígenos Helmínticos/administración & dosificación , Glicosilfosfatidilinositoles/administración & dosificación , Antagonistas de Heparina/administración & dosificación , Inmunoglobulina G/inmunología , Ratones Endogámicos BALB C , Protaminas/administración & dosificación , Esquistosomiasis mansoni/prevención & control , Factores de Tiempo , Vacunas de ADN/administración & dosificaciónRESUMEN
In previous studies, cytoplasmic repetitive antigen (CRA) and flagellar repetitive antigen (FRA) proteins induced specific humoral and cellular immune responses in susceptible and resistant mice in the absence of Trypanosoma cruzi infection with a significant induction of the Interferon-gamma (IFN-gamma) production in those animals. In this follow-up paper, the immunostimulatory and protective effects of these proteins were evaluated by immunizing with CRA or FRA antigens, BALB/c and C57BL/6 mice and challenging with a T. cruzi (Y strain). Both proteins induced humoral response with high levels of IgG isotypes as well as cellular immunity with high levels of IFN-gamma when compared to controls. However, the lymphocyte proliferative response was minimal. The survival rate at 30 days post-infection was significant in CRA (60%) or FRA (50%)--immunized BALB/c mice and CRA (83.3%)--immunized C57BL/6 mice. Taken as a whole these findings indicate that CRA and FRA are immunogenic and potentially important for protective immunity.
Asunto(s)
Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/inmunología , Enfermedad de Chagas/inmunología , Proteínas Recombinantes/inmunología , Trypanosoma cruzi/inmunología , Animales , Antígenos de Protozoos/administración & dosificación , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Inmunidad Celular , Inmunoglobulina G/sangre , Interferón gamma/análisis , Linfocitos/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Proteínas Recombinantes/administración & dosificaciónRESUMEN
In the present report we analyzed the levels of IgG1, IgG2a, IgG2b and IgG3 isotypes from Balb/c mice immunized with cytoplasmic repetitive antigen (CRA), and flagellar repetitive antigen (FRA) of Trypanosoma cruzi. The immunization was done by subcutaneous route three times (20 days apart) and the analysis was performed 14 days after each treatment. CRA-immunized mice produced high levels of all IgG isotypes, mainly IgG3 and IgG1. FRA-immunization elicited only high levels of IgG1.
Asunto(s)
Antígenos de Protozoos/inmunología , Isotipos de Inmunoglobulinas/inmunología , Proteínas Protozoarias/inmunología , Trypanosoma cruzi/inmunología , Animales , Antígenos de Protozoos/administración & dosificación , Inmunoglobulina G/inmunología , Ratones , Ratones Endogámicos BALB C , Proteínas Protozoarias/administración & dosificaciónRESUMEN
A polypeptide chain formed by recombinant antigens, cytoplasmic repetitive antigen (CRA) and flagellar repetitive antigen (FRA) (CF-Chimera) of Trypanosoma cruzi, was adsorbed on gold and platinum electrodes and investigated by electrochemical impedance spectroscopy on phosphate buffer saline solutions (PBS) containing a redox couple. It was found that the adsorption is strongly sensitive to the oxide layer on the electrode surface. In the majority of the experiments the antigens retained their activity as observed through their interaction with sera from chronic chagasic patients. The results expressed in terms of the charge transfer resistance across the interface, indicate the viability of using the impedance methodology for the development of a biosensor for serological diagnosis of Chagas' disease.
Asunto(s)
Anticuerpos/sangre , Complejo Antígeno-Anticuerpo/sangre , Técnicas Biosensibles/instrumentación , Enfermedad de Chagas/sangre , Enfermedad de Chagas/diagnóstico , Impedancia Eléctrica , Electrodos , Inmunoensayo/instrumentación , Anticuerpos/inmunología , Complejo Antígeno-Anticuerpo/inmunología , Técnicas Biosensibles/métodos , Enfermedad de Chagas/inmunología , Materiales Biocompatibles Revestidos/síntesis química , Materiales Biocompatibles Revestidos/química , Electroquímica/instrumentación , Electroquímica/métodos , Diseño de Equipo , Análisis de Falla de Equipo , Oro , Humanos , Inmunoensayo/métodos , Metales , Platino (Metal) , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Pruebas Serológicas/instrumentación , Pruebas Serológicas/métodosRESUMEN
In the present report we analyzed the levels of IgG1, IgG2a, IgG2b and IgG3 isotypes from Balb/c mice immunized with cytoplasmic repetitive antigen (CRA), and flagelar repetitive antigen (FRA) of Trypanosoma cruzi. The immunization was done by subcutaneous route three times (20 days apart) and the analysis was performed 14 days after each treatment. CRA-immunized mice produced high levels of all IgG isotypes, mainly IgG3 and IgG1. FRA-immunization elicited only high levels of IgG1
Asunto(s)
Animales , Ratones , Isotipos de Inmunoglobulinas , Trypanosoma cruzi , Inmunización , Ratones Endogámicos BALB CRESUMEN
In the present communication we analyzed the levels of IgG1, IgG2, IgG3, IgG4 and IgE isotypes to soluble egg antigen of Schistosoma mansoni by ELISA in individuals from an endemic area for schistosomiasis in Northeast Brazil. The analysis was performed before and after treatment to evaluate the age-dependent pattern, and to identify differences in the reactivities to antigens. Our results suggest that schistosomiasis treatment would not interfere with this sort of immune response.
Asunto(s)
Anticuerpos Antihelmínticos/sangre , Antígenos Helmínticos/inmunología , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/inmunología , Animales , Anticuerpos Antihelmínticos/inmunología , Brasil , Ensayo de Inmunoadsorción Enzimática , Heces/parasitología , Humanos , Oxamniquina/uso terapéutico , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomicidas/uso terapéuticoRESUMEN
In the present communication we analyzed the levels of IgG1, IgG2, IgG3, IgG4 and IgE isotypes to soluble egg antigen of Schistosoma mansoni by ELISA in individuals from an endemic area for schistosomiasis in Northeast Brazil. The analysis was performed before and after treatment to evaluate the age-dependent pattern, and to identify differences in the reactivities to antigens. Our results suggest that schistosomiasis treatment would not interfere with this sort of immune response
Asunto(s)
Animales , Humanos , Anticuerpos Antihelmínticos , Antígenos Helmínticos , Inmunoglobulina G , Schistosoma mansoni , Esquistosomiasis mansoni , Brasil , Ensayo de Inmunoadsorción Enzimática , Heces , Oxamniquina , Esquistosomiasis mansoni , EsquistosomicidasRESUMEN
We used the EIE-Recombinant-Chagas-Biomanguinhos kit (EIE-Rec kit) developed by the Oswaldo Cruz Foundation, Brazil, to monitor cure of chagasic patients who were treated during the acute phase of T. cruzi infection. Treated patients were previously studied by parasitological and serological tests and classified as cured patients (CP) (n = 10), dissociated patients (DP) (n = 6), and noncured patients (NCP) (n = 6). When sera of these patients were assayed by EIE-Rec kit all sera from NCP and all sera from CP showed positive and negative reactions, respectively. These results were in full agreement with those obtained previously by the classical tests. Two DP showed a positive reaction; the remaining four displayed a negative reaction, similar to that observed in sera from nonchagasic (NCh) individuals, and could therefore be considered CP. Our results suggest that the EIE-Rec kit could be used to monitor the efficacy of Chagas' disease treatment.
Asunto(s)
Enfermedad de Chagas/diagnóstico , Enfermedad de Chagas/terapia , Juego de Reactivos para Diagnóstico , Anticuerpos Antiprotozoarios/análisis , Antígenos de Protozoos , Brasil , Enfermedad de Chagas/inmunología , Reacciones Cruzadas , Ensayo de Inmunoadsorción Enzimática , Estudios de Seguimiento , Humanos , Proteínas Recombinantes , Sensibilidad y EspecificidadRESUMEN
A kit based on an enzyme immunoassay, EIE-Recombinant-Chagas-Biomanguinhos, developed by the Oswaldo Cruz Foundation, was evaluated for the serodiagnosis of chronic Chagas disease. Evaluation was performed with 368 serum samples collected from individuals living in an endemic area for Chagas disease: 131 patients in the chronic phase with confirmed clinical, epidemiological, and serological diagnosis (indirect immunofluorescence, indirect hemagglutination or enzyme-linked immunosorbent assay) and 237 nonchagasic seronegative individuals were considered negative control. The EIE-Recombinant-Chagas-Biomanguinhos kit showed high sensitivity, 100 percent (CI 95 percent: 96.4-100 percent) and high specificity, 100 percent (CI 95 percent: 98-100 percent). The data obtained were in full agreement with clinical and conventional serology data. In addition, no cross-reaction was observed with sera from patients with cutaneous (n=14) and visceral (n=3) leishmaniasis. However, when these sera were tested by conventional serological assays for Chagas disease, cross-reactions were detected in 14.3 percent and 33.3 percent of the patients with cutaneous and visceral leishmaniasis, respectively. No cross-reactions were observed when sera from nonchagasic seronegative patients bearing other infectious disease (syphilis, n=8; HTLV, n=8; HCV, n=7 and HBV, n=12) were tested. In addition, sera of patients with inconclusive results for Chagas disease by conventional serology showed results in agreement with clinical evaluation, when tested by the kit. These results are relevant and indicate that the refered kit provides a safe immunodiagnosis of Chagas disease and could be used in blood bank screening
Asunto(s)
Humanos , Animales , Preescolar , Niño , Adolescente , Adulto , Persona de Mediana Edad , Antígenos de Protozoos/sangre , Enfermedad de Chagas/diagnóstico , Proteínas Recombinantes/inmunología , Enfermedad de Chagas/sangre , Enfermedad Crónica , Técnicas para Inmunoenzimas/métodos , Sensibilidad y Especificidad , Pruebas Serológicas , Trypanosoma cruzi/inmunologíaRESUMEN
Os polipeptídeos de 46 e 58kDa foram reconhecidos em diferentes cepas de T. cruzi (Y, WSL e Colombiana) pelo soro de todos os pacientes chagásicos estudados. Estes polipeptídeos foram isolados da cepa Y e usados em ELISA. A sensibilidade e especificidade foram 97,6 por cento [CI 95 por cento: 86-100 por cento] e 100 por cento [CI 95 por cento: 89,3-100 por cento], respectivamente quando Tc 46 foi usada. Quando Tc 58 foi utilizada a sensibilidade e especificidade foram de 100 por cento [CI 95 por cento: 89,6-100 por cento] e 90,2 por cento [CI 95 por cento: 75,9-96,8 por cento], respectivamente