Abstract
The rise of drug-resistant strains is a major challenge to containing the tuberculosis (TB) pandemic. Yet, little is known about the extent of resistance in early years of chemotherapy and when transmission of resistant strains on a larger scale became a major public health issue. Here we reconstruct the timeline of the acquisition of antimicrobial resistance during a major ongoing outbreak of multidrug-resistant TB in Argentina. We estimate that the progenitor of the outbreak strain acquired resistance to isoniazid, streptomycin and rifampicin by around 1973, indicating continuous circulation of a multidrug-resistant TB strain for four decades. By around 1979 the strain had acquired additional resistance to three more drugs. Our results indicate that Mycobacterium tuberculosis (Mtb) with extensive resistance profiles circulated 15 years before the outbreak was detected, and about one decade before the earliest documented transmission of Mtb strains with such extensive resistance profiles globally.
Highlights
The rise of drug-resistant strains is a major challenge to containing the tuberculosis (TB) pandemic
whole-genome sequencing (WGS) has led to novel insights into the evolution of Mycobacterium tuberculosis (Mtb) drug resistance
A recent study applying Bayesian evolutionary analyses to WGS data found that public health weaknesses superimposed on a growing bacterial population rather than selection for antimicrobial resistance has likely caused the expansion of the Beijing lineage[7]
Summary
The rise of drug-resistant strains is a major challenge to containing the tuberculosis (TB) pandemic. Little is known about the extent of resistance in early years of chemotherapy and when transmission of resistant strains on a larger scale became a major public health issue. Our results indicate that Mycobacterium tuberculosis (Mtb) with extensive resistance profiles circulated 15 years before the outbreak was detected, and about one decade before the earliest documented transmission of Mtb strains with such extensive resistance profiles globally. A recent study applying Bayesian evolutionary analyses to WGS data found that public health weaknesses superimposed on a growing bacterial population rather than selection for antimicrobial resistance has likely caused the expansion of the Beijing lineage[7]. Little is known about the extent of historical drug resistance, and when transmission of resistant strains on a larger scale became a major public health issue. In a systematic countrywide survey performed in 2003–2009, the M strain showed a declining trend, but still accounted for 29 and 40% of MDR- and XDR-TB cases, respectively, and as such still represents the largest ongoing outbreak of MDR-TB in Argentina[22]
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