Publications (2)4.11 Total impact
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ABSTRACT: To establish and evaluate the Chinese rhesus model of tuberculosis. Twelve Chinese rhesus macaques, randomly divided into 3 groups, were inoculated with 2 different doses of Mycobacterium tuberculosis H(37) Rv strain via both bronchoscopic and intratracheal instillation into the lungs. Clinical observation and laboratory examinations were performed, including erythrocyte sedimentation rate, C-reactive protein, tuberculin skin test and X-ray examination. Histopathological assessments were performed in the 24th week postinfection. Statistical analysis was performed by ANOVA in the 3 groups. After infection all the animals manifested fever, weight lose, lack of appetite, coughing and other symptoms of tuberculosis. The temperature gradually increased and reached a peak [(40.1 ± 0.2)°C] at the 8th week postinfection. The weight decreased significantly at 24th week postinfection (-5.5 ± 5.6)%. Erythrocyte sedimentation rate elevated significantly at the 6th to 8th week postinfection (36 ± 40) mm/1 h. C-reactive protein was significantly increased at the 6th to 24th week after infection (75.8 ± 49.8) mg/L. The positive rate of tuberculin skin test was 100%. In Group I (bronchoscopic instillation, 20 CFU) the disease developed slowly, and the main manifestation of chest X-ray was patchy shadows. In group II (bronchoscopic instillation, 100 CFU) and group III (intratracheal instillation, 100 CFU) the disease developed rapidly, and the main manifestation of chest X-ray was patchy and nodular lesions during the 4th to the 12th week postinfection, but became large patchy and consolidation lesions during the 12th to the 24th week postinfection. Tuberculosis granuloma and caseous necrosis, similar to the pathological changes of human tuberculosis, were found in the lungs, mediastinal lymph nodes, kidney and spleen. The results of acid-fast stain were positive. The most serious pathological manifestations were observed in group II, followed by group III and group I. The highest bacterial load of the right lung was seen in group II, followed by group I and group III. A chinese rhesus model of tuberculosis was successfully developed via both bronchoscopic and intratracheal instillation. Their clinical manifestations, disease progression and pathological changes were similar to human primary tuberculosis and hematogenous disseminated tuberculosis.
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ABSTRACT: Mycobacterium tuberculosis is the most common communicable infectious disease worldwide and the top killer of human immunodeficiency virus (HIV)-infected people. Because of common dual HIV and M. tuberculosis infections, the emergence of multidrug-resistant M. tuberculosis strains, the lack of effective vaccination, the morbidity, and the mortality of M. tuberculosis infection are increasing sharply. Therefore, there is an urgent need for vaccine and drug development against M. tuberculosis infection. These require appropriate animal models that closely resemble human disease. To this end, we infected Chinese rhesus macaques with the M. tuberculosis H37Rv strain. Bronchoscopy was used to inoculate nine monkeys with different doses of M. tuberculosis H37Rv strain. Regardless of the M. tuberculosis dose, all monkeys were infected successfully. This was shown by clinical, laboratory, and histopathology assessments. Among nine infected monkeys, six developed acute rapid progressive tuberculosis and the remaining animals mirrored early-stage chronic disease. These data, taken together, demonstrate that Chinese rhesus macaques are highly susceptible to M. tuberculosis infection and develop similar manifestations of disease that are seen in humans. This model affords new opportunities for studies of M. tuberculosis disease pathology and therapeutics.
Wuhan UniversityWu-han-shih, Hubei, China