Strain-related virulence of the dominant Mycobacterium tuberculosis strain in the Canadian province of Manitoba.

SETTING: The Canadian province of Manitoba. OBJECTIVE: To confirm the putative hypervirulence observed in Mycobacterium tuberculosis Type1 strain and further characterize the progression and manifestation of pulmonary tuberculosis caused by this strain in comparison to other common clinical isolates from Manitoba. DESIGN: C3H and BALB/c mice were exposed to aerosols either of Type1, Type2, Type5, Type72 or H37Rv strain to study their respective survival profiles. Additionally, bacillary loads and lung histology were examined at 15 days post-exposure. RESULTS: In both mouse models, Type-1 infected mice succumbed to disease significantly earlier than other strains (p < or =0.0002). Differences between average log(10) CFU values between clinical isolates were less than 1log(10) difference. In C3H mice, the amount of granulomatous inflammation was highest in Type1 infected mice but not significantly different than all clinical strains. In contrast, BALB/c mice infected with Type1 induced the lowest amount of granulomatous inflammation compared to other clinical isolates. CONCLUSION: Our results indicate that although mice infected with the Type1 strain died significantly earlier than mice infected with other clinical strains in both C3H and BALB/c mice, the hypervirulence of the Type1 strain is not attributed to the growth rate of the organism, as differences in growth between clinical M. tuberculosis isolates were insignificant.

Identification of a predominant isolate of Mycobacterium tuberculosis using molecular and clinical epidemiology tools and in vitro cytokine responses.

BACKGROUND: Tuberculosis (TB) surveillance programs in Canada have established that TB in Canada is becoming a disease of geographically and demographically distinct groups. In 1995, treaty status aboriginals from the province of Manitoba accounted for 46% of the disease burden of this sub-group in Canada. The TB incidence rates are dramatically high in certain reserves of Manitoba and are equivalent to rates in African countries. The objective of our study was to identify prevalent isolates of Mycobacterium tuberculosis in the patient population of Manitoba using molecular epidemiology tools, studying the patient demographics associated with the prevalent strain and studying the in vitro cytokine profiles post-infection with the predominant strain. METHODS: Molecular typing was performed on all isolates available between 1992 to 1997. A clinical database was generated using patient information from Manitoba. THP-1 cells were infected using strains of M. tuberculosis and cytokine profiles were determined using immunoassays for cytokines IL-1beta, IL-10, IL-12, IFN-gamma and TNF-alpha. RESULTS: In Manitoba, 24% of the disease burden is due to a particular M. tuberculosis strain (Type1). The strain is common in patients of aboriginal decent and is responsible for at least 87% of these cases. Cytokine assays indicate that the Type1 strain induces comparatively lower titers of IL-1beta, IFN-gamma and TNF-alpha in infected THP-1 cells as compared to H37Ra and H37Rv strains. CONCLUSION: In Manitoba, Type1 strain is predominant in TB patients. The majority of the cases infected with this particular strain are newly active with a high incidence of respiratory disease, positive chest radiographs and pulmonary cavities. In vitro secretion of IL-1beta, IFN-gamma and TNF-alpha is suppressed in Type1 infected culture samples when compared to H37Ra and H37Rv infected cells.