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

SOURCE: Emerging Infectious Diseases
OUTPUT TYPE: Journal Article
TITLE AUTHOR(S): M.Klopper, R.M.Warren, C.Hayes, N.C.G.Van Pittius, E.M.Streicher, B.Muller, F.A.Sirgel, M.Chabula-Nxiweni, E.Hoosain, G.Coetzee, P.D.Van Helden, T.C.Victor, A.P.Trollip
DEPARTMENT: Human and Social Capabilities (HSC)
Print: HSRC Library: shelf number 7676

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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.