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1.
J Infect Dis ; 227(11): 1322-1332, 2023 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-36571148

RESUMO

BACKGROUND: A drawback in the treatment of chronic Chagas disease (American trypanosomiasis) is the long time required to achieve complete loss of serological reactivity, the standard for determining treatment efficacy. METHODS: Antibody-secreting cells and memory B cells specific for Trypanosoma cruzi and their degree of differentiation were evaluated in adult and pediatric study participants with chronic Chagas disease before and after etiological treatment. RESULTS: T. cruzi-specific antibody-secreting cells disappeared from the circulation in benznidazole or nifurtimox-treated participants with declining parasite-specific antibody levels after treatment, whereas B cells in most participants with unaltered antibody levels were low before treatment and did not change after treatment. The timing of the decay in parasite-specific antibody-secreting B cells was similar to that in parasite-specific antibodies, as measured by a Luminex-based assay, but preceded the decay in antibody levels detected by conventional serology. The phenotype of total B cells returned to a noninfection profile after successful treatment. CONCLUSIONS: T. cruzi-specific antibodies in the circulation of chronically T. cruzi-infected study participants likely derive from both antigen-driven plasmablasts, which disappear after successful treatment, and long-lived plasma cells, which persist and account for the low frequency and long course to complete seronegative conversion in successfully treated participants.


Assuntos
Doença de Chagas , Nitroimidazóis , Tripanossomicidas , Trypanosoma cruzi , Humanos , Trypanosoma cruzi/genética , Doença de Chagas/tratamento farmacológico , Nitroimidazóis/uso terapêutico , Resultado do Tratamento , Linfócitos B , Nifurtimox/uso terapêutico , Infecção Persistente , Tripanossomicidas/uso terapêutico , Doença Crônica
2.
J Antimicrob Chemother ; 68(2): 424-37, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23104493

RESUMO

OBJECTIVES: Even though the use of combined drugs has been proved to be effective in other chronic infections, assessment of combined treatment of antiparasitic drugs in human Chagas' disease has not been performed. Herein, a pilot study was conducted to evaluate the tolerance and side effects of a sequential combined treatment of two antiparasitic drugs, allopurinol and benznidazole, in the chronic phase of Trypanosoma cruzi infection. PATIENTS AND METHODS: Changes in total and T. cruzi-specific T and B cells were monitored during a median follow-up of 36 months. Allopurinol was administered for 3 months (600 mg/day) followed by 30 days of benznidazole (5 mg/kg/day) in 11 T. cruzi-infected subjects. RESULTS: The combined sequential treatment of allopurinol and benznidazole was well tolerated. The levels of T. cruzi-specific antibodies significantly decreased after sequential combined treatment, as determined by conventional serology and by a multiplex assay using recombinant proteins. The frequency of T. cruzi-specific interferon-γ-producing T cells significantly increased after allopurinol treatment and decreased to background levels following benznidazole administration in a substantial proportion of subjects evaluated. The levels of total naive (CD45RA + CCR7 + CD62L+) CD4 + and CD8 + T cells were restored after allopurinol administration and maintained after completion of the combined drug protocol, along with a decrease in T cell activation in total peripheral CD4 + and CD8 + T cells. CONCLUSIONS: This pilot study shows that the combination of allopurinol and benznidazole induces significant modifications in T and B cell responses indicative of a reduction in parasite burden, and sustains the feasibility of administration of two antiparasitic drugs in the chronic phase of Chagas' disease.


Assuntos
Alopurinol/administração & dosagem , Antiprotozoários/administração & dosagem , Doença de Chagas/tratamento farmacológico , Nitroimidazóis/administração & dosagem , Adulto , Alopurinol/efeitos adversos , Antiprotozoários/efeitos adversos , Linfócitos B/imunologia , Doença Crônica , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Nitroimidazóis/efeitos adversos , Projetos Piloto , Linfócitos T/imunologia , Resultado do Tratamento , Trypanosoma cruzi/imunologia
3.
Parasitology ; 132(Pt 6): 867-82, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16700961

RESUMO

The Trypanosoma cruzi cyclophilin gene family comprises 15 paralogues whose nominal masses vary from 19 to 110 kDa, namely TcCyP19, TcCyP20, TcCyP21, TcCyP22, TcCyP24, TcCyP25, TcCyP26, TcCyP28, TcCyP29, TcCyP30, TcCyP34, TcCyP35, TcCyP40, TcCyP42 and TcCyP110. Under the conditions used, only some of the T. cruzi cyclophilin paralogue products could be isolated by affinity chromatography. The 15 paralogues were aligned with 495 cyclophilins from diverse organisms. Analyses of clusters formed by the T. cruzi cyclophilins with others encoded in various genomes revealed that 8 of them (TcCyP19, TcCyP21, TcCyP22, TcCyP24, TcCyP35, TcCyP40, TcCyP42 and TcCyP110) have orthologues in many different genomes whereas the other 7 display less-defined patterns of their sequence attributes and their classification to a specific group of cyclophilin's orthologues remains uncertain. Seven epimastigote cDNA clones encoding cyclophilin isoforms were further studied. These genes were found dispersed throughout the genome of the parasite. Amastigote and trypomastigote mRNAs encoding these 7 genes were also detected. We isolated 4 cyclosporin A-binding proteins in T. cruzi epimastigote extracts, which were identified by mass spectrometry as TcCyP19, TcCyP22, TcCyP28 and TcCyP40. Cyclosporin A-binding to these cyclophilins might be of importance to the mechanism of action of Cyclosporin A and its non-immunosuppressive analogues, whose trypanocidal effects were previously reported, and therefore, of potential interest in the chemotherapy of Chagas' disease.


Assuntos
Ciclofilinas/genética , Ciclosporina/metabolismo , Expressão Gênica/fisiologia , Proteínas de Protozoários/genética , Trypanosoma cruzi/genética , Sequência de Aminoácidos , Animais , Cromatografia de Afinidade/veterinária , Ciclofilinas/química , Ciclofilinas/classificação , Primers do DNA/química , Ordem dos Genes , Genoma/genética , Humanos , Estágios do Ciclo de Vida/genética , Dados de Sequência Molecular , Proteínas de Protozoários/química , Proteínas de Protozoários/classificação , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Alinhamento de Sequência/veterinária , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/veterinária , Trypanosoma cruzi/química
4.
Am J Trop Med Hyg ; 49(2): 254-9, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8357088

RESUMO

A group of 358 owl and squirrel monkeys imported from Colombia, Peru, and Bolivia for the U.S. Agency for International Development Malaria Vaccine Development Program was examined for trypanosomes and microfilariae. Trypanosoma rangeli, isolated by hemoculture from Aotus nancymai, Saimiri b. boliviensis, and S. b. peruviensis, accounted for 76.6% of all trypanosome infections. Trypanosoma cruzi was isolated from 25 of 194 S. b. boliviensis, including two mixed infections with T. rangeli. Identifications of trypanosomes were confirmed by blinded tests with a panel of five rRNA probes on a subsample of cultures identified morphologically. Although no trypanosomes were isolated from Aotus vociferans or A. lemurinus griseimembra, positive serologic responses to T. cruzi were observed by indirect immunofluorescence assay in all species of monkeys examined and ranged from 42.1% among S. b. peruviensis to 92.3% among A. vociferans. Among T. rangeli-infected monkeys, 43.7% were seronegative for T. cruzi. No microfilariae were found in S. b. boliviensis or A. l. griseimembra. Mansonella barbascalensis and Dipetalonema caudispina were observed in A. vociferans, M. panamensis in A. nancymai, and M. saimiri and D. caudispina in S. b. peruviensis. Such naturally occurring infections in imported animal models are potential sources of accidental transmission to animal handlers and uninfected laboratory animals and can introduce confounding variables into otherwise well-planned and well-executed studies.


Assuntos
Aotus trivirgatus/parasitologia , Filariose/veterinária , Doenças dos Macacos/epidemiologia , Saimiri/parasitologia , Tripanossomíase/veterinária , Animais , Anticorpos Antiprotozoários/sangue , Bolívia/epidemiologia , Doença de Chagas/epidemiologia , Doença de Chagas/veterinária , Infecções por Dipetalonema/epidemiologia , Infecções por Dipetalonema/veterinária , Filariose/epidemiologia , Mansonelose/epidemiologia , Mansonelose/veterinária , Microfilárias/isolamento & purificação , Peru/epidemiologia , Prevalência , Trypanosoma/imunologia , Trypanosoma/isolamento & purificação , Trypanosoma cruzi/imunologia , Trypanosoma cruzi/isolamento & purificação , Tripanossomíase/epidemiologia
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