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Free Content Course of murine tuberculosis and response to first-line therapy depends on route of infection and inoculum size

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BACKGROUND: In the search for new anti-tuberculosis drugs, numerous potential drugs are being screened in vitro. In animal models, promising new anti-tuberculosis drugs are assessed in terms of toxic side effects and comparative therapeutic efficacy. Mice are frequently used and experimental infections are established in different ways. OBJECTIVE: To investigate to what extent the route of Mycobacterium tuberculosis inoculation is a determinant in the pathogenesis of tuberculosis (TB) and the therapeutic outcome. Results will contribute to insight into the translational value of TB models used for preclinical studies. DESIGN: TB in mice was established through intratracheal or intravenous mycobacterial inoculation. The efficacy of a 26-week treatment regimen was evaluated, including assessment of relapse of infection 13 weeks post-treatment. RESULTS: It was shown that the course of TB and the therapeutic response, in terms of histopathological char- acteristics and mycobacterial load, in lungs and extra- pulmonary organs is substantially different and depend- ent on the route of infection applied and the inoculum size used. CONCLUSION: When evaluating the comparative thera- peutic potential of novel anti-tuberculosis drugs or drug treatment schedules investigated in different studies, it should be noted that the route of infection applied and the inoculum size used influence the course of murine TB and the therapeutic response to the standard first- line anti-tuberculosis drug regimen.
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Keywords: ANIMAL MODEL; ROUTE OF INFECTION; TUBERCULOSIS

Document Type: Research Article

Affiliations: 1: Erasmus MC, Department of Medical Microbiology and Infectious Diseases, University Medical Centre Rotterdam, Rotterdam, The Netherlands 2: Department of Pathology, Section of Experimental Pathology, National Institute of Medical Sciences and Nutrition Salvador Zubiran, Mexico City, Mexico

Publication date: November 1, 2011

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

    Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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