Emergence and spread of extensively and totally drug-resistant tuberculosis, South Africa

Klopper, Marisa ; Warren, Robin Mark ; Hayes, Cindy ; Gey van Pittius, Nicolaas Claudius ; Streicher, Elizabeth Maria ; Muller, Borna ; Sirgel, Frederick Adriaan ; Chabula-Nxiweni, Mamisa ; Hoosain, Ebrahim ; Coetzee, Gerrit ; Van Helden, Paul David ; Victor, Thomas Calldo ; Trollip, Andre Phillip (2013-03)

CITATION: Klopper, M. et al. 2013. Emergence and spread of extensively and totally drug-resistant tuberculosis, South Africa. Emerging Infectious Diseases, 19(3):449-455, doi:10.3201/eid1903.120246.

The original publication is available at http://wwwnc.cdc.gov/eid


Factors driving the increase in drug-resistant tuberculosis (TB) in the Eastern Cape Province, South Africa, are not understood. A convenience sample of 309 drug-susceptible and 342 multidrug-resistant (MDR) TB isolates, collected July 2008–July 2009, were characterized by spoligotyping, DNA fingerprinting, insertion site mapping, and targeted DNA sequencing. Analysis of molecular-based data showed diverse genetic backgrounds among drug-sensitive and MDR TB sensu stricto isolates in contrast to restricted genetic backgrounds among pre–extensively drug-resistant (pre-XDR) TB and XDR TB isolates. Second-line drug resistance was significantly associated with the atypical Beijing genotype. DNA fingerprinting and sequencing demonstrated that the pre-XDR and XDR atypical Beijing isolates evolved from a common progenitor; 85% and 92%, respectively, were clustered, indicating transmission. Ninety-three percent of atypical XDR Beijing isolates had mutations that confer resistance to 10 anti-TB drugs, and some isolates also were resistant to para-aminosalicylic acid. These findings suggest the emergence of totally drug-resistant TB.

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