Limited tuberculosis progression in guinea pigs naturally exposed to human multidrug resistant strains.
Dharmadhikari-AS; Basaraba-R; Palanisamy-G; Venter-K; Mphahlele-M; Jensen-P; First-M; Parsons-S; Weyer-K; Nardell-EA
Am J Respir Crit Care Med 2009 Apr; 179(Meeting Abstracts):A5290
Rationale: Multidrug resistant M. tuberculosis (MDR-TB) infections are a major source of morbidity and mortality worldwide. Some laboratory and epidemiologic studies, however, suggest that MDR-TB strains display heterogeneous fitness. Animal models of TB have been used to study MDR-TB pathogenesis, but these studies have used cultivated MDR-TB strains that are aerosolized in relatively high concentrations compared to natural infection. Little is known about whether MDR-TB aerosols generated directly from humans propagate differently in sentinel animals. Methods: Using a unique airborne infections research facility in South Africa, we exposed 362 guinea pigs (GP) to exhaust air from a 6-bed MDR-TB hospital ward over a 4 month period and performed monthly tuberculin skin tests (TST) on them. To accelerate disease progression and enhance microbial recovery rate, we pharmacologically immunosuppressed half the TST positive animals after MDR-TB exposure and examined and scored lung and spleen tissues for pathology. Results: Although 74% of GPs acquired infection (e.g. had positive TST), only 15% of TST positive GPs had pathologic evidence of TB. We also noted TST reversions in more than 20% of TST positive GPs. Less pathology was found in GPs with TST reactions of the longest duration. Steroid immunosuppression did not alter disease prevalence or severity. Conclusions: Even in the highly vulnerable GP model, most (but not all) MDR-TB strains naturally generated by our patients failed to progress to disease, suggesting reduced fitness.
Aerosol-generators; Aerosol-particles; Biological-factors; Cell-biology; Cell-function; Disease-incidence; Disease-transmission; Epidemiology; Exhaust-ventilation; Exposure-assessment; Exposure-levels; Exposure-methods; Inhalation-studies; Laboratory-animals; Laboratory-testing; Lung-disorders; Lung-irritants; Mathematical-models; Morbidity-rates; Mortality-rates; Physiological-effects; Pulmonary-system-disorders; Skin-tests; Statistical-analysis; Work-environment
American Journal of Respiratory and Critical Care Medicine