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. 2013 Mar;19(3):449-55.
doi: 10.3201//EID1903.120246.

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

Marisa Klopper  1 , Robin Mark Warren, Cindy Hayes, Nicolaas Claudius Gey van Pittius, Elizabeth Maria Streicher, Borna Müller, Frederick Adriaan Sirgel, Mamisa Chabula-Nxiweni, Ebrahim Hoosain, Gerrit Coetzee, Paul David van Helden, Thomas Calldo Victor, André Phillip Trollip
Affiliations

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

Marisa Klopper et al. Emerg Infect Dis. 2013 Mar.

Abstract

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.

Keywords: MDR TB; Mycobacterium tuberculosis; South Africa; TB; Tuberculosis; XDR-TB; bacteria; extensively drug-resistant tuberculosis; mycobacteria; totally drug resistant TB.

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Figure
District municipalities in the Eastern Cape Province, South Africa. Map courtesy of F.W. van Zyl.
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