Journal
INFECTION AND IMMUNITY
Volume 71, Issue 10, Pages 5831-5844Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.71.10.5831-5844.2003
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Funding
- NHLBI NIH HHS [R01 HL 68526, R01 HL068526] Funding Source: Medline
- NIAID NIH HHS [R01 AI 47485, R01 AI047485] Funding Source: Medline
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Nonhuman primates were used to develop an animal model that closely mimics human Mycobacterium tuberculosis infection. Cynomolgus macaques were infected with low doses of virulent M. tuberculosis via bronchoscopic instillation into the lung. All monkeys were successfully infected, based on tuberculin skin test conversion and peripheral immune responses to M. tuberculosis antigens. Progression of infection in the 17 monkeys studied was variable. Active-chronic infection, observed in 50 to 60% of monkeys, was characterized by clear signs of infection or disease on serial thoracic radiographs and in other tests and was typified by eventual progression to advanced disease. Approximately 40% of monkeys did not progress to disease in the 15 to 20 months of study, although they were clearly infected initially. These monkeys had clinical characteristics of latent tuberculosis in humans. Low-dose infection of cynomolgus macaques appears to represent the full spectrum of human M. tuberculosis infection and will be an excellent model for the study of pathogenesis and immunology of this infection. In addition, this model will provide an opportunity to study the latent M. tuberculosis infection observed in similar to90% of all infected humans.
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