No abstract

Background & objectives:Studies have shown the bactericidal potential of econazole and clotrimazole against Mycobacterium tuberculosis under in vitro and ex vivo conditions along with their synergism with conventional antituberculosis drugs. These molecules were also found to be effective against different multidrug resistant (MDR) M. tuberculosis isolates in vitro. Hence the present study was designed to evaluate the in vivo antimycobacterial potential of moxifloxacin and econazole alone and in combination against multidrug resistant tuberculosis (MDR-TB) in a mice model.Methods:Mice were infected with 2.5×107 bacilli of MDR strain of M. tuberculosis by aerosol route of infection. After four weeks of infection, chemotherapy was started orally by moxifloxacin 8.0 mg/kg body wt and econazole 3.3 mg/kg alone and in combination, as well as with four first line anti-tuberculosis drugs as a positive control. The animals were sacrificed and the lungs and spleen were excised under aspetic conditions. The tissues were homogenized with sterile normal saline, an aliquot of the homogenate was plated on Middlebrook 7H11 agar supplemented with oleate albumin dextrose catalase (OADC) and incubated at 37°C for four weeks. The number of visible and individual colonies were counted.Results:The first line anti-tuberculosis drugs (RIF+INH+EMB+PZA) after eight weeks of therapy had no impact as the bacillary load in lungs and spleens remained unchanged. However, econazole, moxifloxacin alone as well as in combination significantly reduced the bacillary load in lungs as well as in spleens of MDR-TB bacilli infected mice.Interpretation & conclusions:Co-administration of the two drugs (econazole and moxifloxacin) to MDR-TB strain JAL-7782 infected mice exhibited additive effect, the efficacy of the drugs in combination being higher as compared with ECZ or MOX alone. These results were substantiated by histopathological studies. This study suggests the utility of econazole for the treatment of MDR tuberculosis and warrants further work in this direction.

No abstract

Aims and objectives: Tuberculosis (TB) remain a leading cause of death globally among among infectious diseases that has killed more number of people than any other infectious diseases. It was Robert Koch who recognized the spectrum of pathology of tuberculosis (TB) in different animal species. Methods: The examination of clinical specimens from infected humans and animals confirmed the variable patterns of pathological reactions in different animal species. Guinea pigs are innately susceptible while humans, mice and rabbits show different level of resistance depending upon their genotype. The studies of TB in laboratory animals like mice, rabbits and guinea pigs have significantly increased the understanding of the aetiology, viurulence, and pathogenesis of the disease. By introducing less than five virulence organisms into guinea pigs by the respiratory route can produce lung lesions, bacteraemia and fatal diseases, which has helped the extrapolation of results of such experiments to humans beings. The similarities in the course of course of clinical infection between guinea pigs and humans allow us to model different models of TB and to evaluate the protective efficacy of candidate in such systems. The only limitation of this model is a dearth of immunogical reagents required for the qualitative and quantitative evaluation of the immune responses, special reference to cytokines and cell phenotypes. Further limitation is the higher cost of the guinea pigs as compared with the mice. Results: The rabbit is relatively resistant to M TB infection, however following infection with virulent Mycobacterium bovis, the rabbit produces pulmonary cavities like humans. The rabbit model, however, is also limited by the lack of immunological reagents. Mice are the animal choice of studying the immunology of Mycobacterial infections and contributed much to our current understanding of the roles of various immunological mechanisms of resistance. The resistance of mice to the development of classic TB disease, however, represents a significant disadvantage to the mouse model. Although non-human primates are closely related to humans, owing to high cost and handing difficulties they have not been exploited to a large extent. Conclusions: As all existing animal models fall to mimic the human disease perfectly, efforts should be focused on the development of the non-human primate (s) as the alternative animal model for TB.

No abstract