title: Emergence and spread of extensively and totally drug-resistant tuberculosis, South Africa.
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.
authors.affiliation: Stellenbosch University, Cape Town, South Africa.
authors.forename: Marisa
authors.initials: M
authors.lastname: Klopper
authors.forename: Robin Mark
authors.initials: RM
authors.lastname: Warren
authors.forename: Cindy
authors.initials: C
authors.lastname: Hayes
authors.forename: Nicolaas Claudius
authors.initials: NC
authors.lastname: Gey van Pittius
authors.forename: Elizabeth Maria
authors.initials: EM
authors.lastname: Streicher
authors.forename: Borna
authors.initials: B
authors.lastname: Müller
authors.forename: Frederick Adriaan
authors.initials: FA
authors.lastname: Sirgel
authors.forename: Mamisa
authors.initials: M
authors.lastname: Chabula-Nxiweni
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Hoosain
authors.forename: Gerrit
authors.initials: G
authors.lastname: Coetzee
authors.forename: Paul
authors.initials: P
authors.lastname: David van Helden
authors.forename: Thomas Calldo
authors.initials: TC
authors.lastname: Victor
authors.forename: André Phillip
authors.initials: AP
authors.lastname: Trollip
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D002374:Catalase / Q000235:genetics; D016000:Cluster Analysis; D021821:Communicable Diseases, Emerging / Q000188:drug therapy / Q000453:epidemiology*; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D020125:Mutation, Missense; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D013019:South Africa / Q000453:epidemiology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis
keywords: MDR TB; Mycobacterium tuberculosis; South Africa; TB; Tuberculosis; XDR-TB; bacteria; extensively drug-resistant tuberculosis; mycobacteria; totally drug resistant TB