Institut Pasteur de Tunis Tunisia
Title: A ten-year evolution of a multidrug-resistant tuberculosis (MDR-TB) outbreak in an HIV-negative context, Tunisia (2001-2011)
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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