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1.
J Zoo Wildl Med ; 50(1): 7-15, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31120657

RESUMO

Bovine tuberculosis (bTB), caused by Mycobacterium bovis infection, causes morbidity and mortality in free-ranging lions in bTB-endemic areas of South Africa. However, the only currently used diagnostic test is the tuberculin skin test (TST). This test is logistically challenging to perform because it requires immobilization of lions twice in a 72-hr period. Blood-based diagnostic tests, such as serological assays, have been previously reported for M. bovis detection in lion populations, and have the advantage of only requiring a single immobilization. In addition, serological assays can be used for retrospective testing. Therefore, the aim of this study was to test free-ranging lions with the STAT-PAKt (Chembio Diagnostics Systems, Medford, NY 11763, USA) and DPPt VetTB (Chembio Diagnostics Systems) serological assays and compare those results with the tuberculin skin test. The serological assays were also used to determine prevalence in bTB-endemic and uninfected lion populations. The results showed that the serological assays could distinguish between M. bovis culture-positive and -negative lions. In addition, antigen-specific humoral responses were present in lions that had clinical signs of bTB disease or were shedding M. bovis antemortem. Although the seroprevalence of M. bovis infection in Kruger National Park lions was similar to that obtained from antemortem mycobacterial culture (4.8 and 3.3%, respectively), it was less than that estimated by the TST (72%). These findings support the hypothesis that assays based on cell-mediated immune responses are more sensitive than serology is in detecting M. bovis infection in lions. However, serological assays can have a role in bTB disease detection in lions and are especially useful for retrospective studies.


Assuntos
Leões , Mycobacterium bovis/isolamento & purificação , Tuberculose/veterinária , Animais , Prevalência , Estudos Soroepidemiológicos , África do Sul/epidemiologia , Teste Tuberculínico/veterinária , Tuberculose/diagnóstico , Tuberculose/epidemiologia
2.
Nat Genet ; 50(2): 307-316, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29358649

RESUMO

To characterize the genetic determinants of resistance to antituberculosis drugs, we performed a genome-wide association study (GWAS) of 6,465 Mycobacterium tuberculosis clinical isolates from more than 30 countries. A GWAS approach within a mixed-regression framework was followed by a phylogenetics-based test for independent mutations. In addition to mutations in established and recently described resistance-associated genes, novel mutations were discovered for resistance to cycloserine, ethionamide and para-aminosalicylic acid. The capacity to detect mutations associated with resistance to ethionamide, pyrazinamide, capreomycin, cycloserine and para-aminosalicylic acid was enhanced by inclusion of insertions and deletions. Odds ratios for mutations within candidate genes were found to reflect levels of resistance. New epistatic relationships between candidate drug-resistance-associated genes were identified. Findings also suggest the involvement of efflux pumps (drrA and Rv2688c) in the emergence of resistance. This study will inform the design of new diagnostic tests and expedite the investigation of resistance and compensatory epistatic mechanisms.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Tuberculose Extensivamente Resistente a Medicamentos/microbiologia , Genoma Bacteriano , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Antituberculosos/uso terapêutico , DNA Bacteriano/análise , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Variação Genética , Estudo de Associação Genômica Ampla , Geografia , Humanos , Testes de Sensibilidade Microbiana , Mutação , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/isolamento & purificação , Filogenia , Análise de Sequência de DNA , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
3.
Int J Exp Pathol ; 84(6): 289-304, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14748748

RESUMO

Classic studies of tuberculosis (TB) revealed morphologic evidence of considerable heterogeneity of macrophages (MØs), but the functional significance of this heterogeneity remains unknown. We have used newly available specific antibodies for selected membrane and secretory molecules to examine the phenotype of MØs in situ in a range of South African patients with TB, compared with sarcoidosis. Patients were human immunodeficiency virus-negative adults and children, and the examined biopsy specimens included lung and lymph nodes. Mature pulmonary MØs (alveolar, interstitial, epithelioid and multinucleated giant cells) selectively expressed scavenger receptor type A and a novel carboxypeptidase-like antigen called carboxypeptidase-related vitellogenin-like MØ molecule (CPVL). CPVL did not display enhanced expression in sarcoidosis, vs. TB patients, as observed with angiotensin-converting enzyme (ACE), a related molecule. Immunocytochemical studies with surfactant proteins (SP)-A and -D showed that type II alveolar cells expressed these collectins, as did MØs, possibly after binding of secreted proteins. Studies with an antibody specific for the C-terminus of fractalkine, a tethered CX3C chemokine, confirmed synthesis of this molecule by bronchiolar epithelial cells and occasional endothelial cells. These studies provide new marker antigens and extend previous studies on MØ differentiation, activation and local interactions in chronic human granulomatous inflammation in the lung.


Assuntos
Macrófagos/imunologia , Receptores de Lipoproteínas , Sarcoidose Pulmonar/imunologia , Tuberculose Pulmonar/imunologia , Adulto , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Biomarcadores/análise , Carboxipeptidases/metabolismo , Quimiocina CX3CL1 , Quimiocinas CX3C/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Imunofenotipagem , Macrófagos/metabolismo , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Peptidil Dipeptidase A/metabolismo , Proteína A Associada a Surfactante Pulmonar/metabolismo , Proteína D Associada a Surfactante Pulmonar/metabolismo , Receptores Imunológicos/metabolismo , Receptores Depuradores , Sarcoidose Pulmonar/metabolismo , Sarcoidose Pulmonar/patologia , Receptores Depuradores Classe A , Receptores Depuradores Classe B , Tuberculose Pulmonar/metabolismo , Tuberculose Pulmonar/patologia
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