Institut Pasteur de Tunis Tunisia
After obtaining his doctorate in Veterinary Medicine (1988) at the Tunisian National School of Veterinary Medicine, Helmi Mardassi moved to the University of Montreal (Canada) where he completed a master degree in Microbiology and Animal Pathology. In 1996, he obtained his PhD degree in Molecular Virology at the Institut Armand-Frappier (University of Quebec, Canada), and next joined the Biotechnology Research Institute of Montreal for a post-doctoral training. Actually he is leading a research unit focusing on molecular epidemiology, evolution and genetics of Mycobacterium tuberculosis. He has published more than 26 papers in reputed journals.
Basically, almost, if not all, multidrug-resistant tuberculosis (MDR-TB) outbreaks described thus far have expanded among HIV-positive patients. Here we describe the emergence and expansion, through a 10-year period, of a MDR-TB outbreak among non-institutionalized, HIV-negative, and apparently healthy young individuals. Since its identification in September 2001 to June 2011, the outbreak involved 45 individuals (mean age 29.7 yrs; 88.9% male), 17 (37.78%) of which were cured, while 9 (20%) have died. Failure and relapse cases represent 13.33% and 8.89%, respectively. The Haarlem3-ST53 outbreak strain evolved mainly as an 11-banded IS6110 RFLP profile (77.77%), while the remaining (22.23%) strains exhibited one additional band (12-banded). The majority (95.55%) of the outbreak-associated strains displayed the same MIRU-VNTR24 profile. The 12-banded outbreak strains, though less frequent, were significantly more associated with smear positivity [OR=4,333 (0,992-18,938); P = 0.043]. However, there were no significant differences between the 11- and 12-banded strains in terms of epidemiological and treatment outcome parameters Drug susceptibility testing coupled to mutational analysis of drug resistance-conferring genes, revealed that initial transmission involved a strain that is simultaneously resistant to isoniazid, rifampicin, ethambutol, and streptomycin. Secondary resistance to pyrazinamide and second-line drugs was further acquired. Despite frequent cases of non adherence and treatment discontinuation, only one strain evolved to the XDR phenotype. Taken together, the data indicate that MDR-TB outbreaks can successfully evolve and cause substantial death rates among HIV-negative young patients. The study also suggests that despite the concourse of favorable behavioral factors, transition to the XDR phenotype is unlikely to be systematic.
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