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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ROUTE OF INFECTION;
Document Type: Research Article
Erasmus MC, Department of Medical Microbiology and Infectious Diseases, University Medical Centre Rotterdam, Rotterdam, The Netherlands
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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