title: Emergence of increased resistance and extensively drug-resistant tuberculosis despite treatment adherence, South Africa.
abstract: We investigated the emergence and evolution of drug-resistant tuberculosis (TB) in an HIV co-infected population at a South African gold mine with a well-functioning TB control program. Of 128 patients with drug-resistant TB diagnosed during January 2003-November 2005, a total of 77 had multidrug-resistant (MDR) TB, 26 had pre-extensively drug-resistant TB (XDR TB), and 5 had XDR TB. Genotyping suggested ongoing transmission of drug-resistant TB, and contact tracing among case-patients in the largest cluster demonstrated multiple possible points of contact. Phylogenetic analysis demonstrated stepwise evolution of drug resistance, despite stringent treatment adherence. These findings suggested that existing TB control measures were inadequate to control the spread of drug-resistant TB in this HIV co-infected population. Diagnosis delay and inappropriate therapy facilitated disease transmission and drug-resistance. These data call for improved infection control measures, implementation of rapid diagnostics, enhanced active screening strategies, and pharmacokinetic studies to determine optimal dosages and treatment regimens.
authors.affiliation: West Vaal Hospital, Orkney, South Africa.
authors.forename: Alistair D
authors.initials: AD
authors.lastname: Calver
authors.forename: Alecia A
authors.initials: AA
authors.lastname: Falmer
authors.forename: Megan
authors.initials: M
authors.lastname: Murray
authors.forename: Odelia J
authors.initials: OJ
authors.lastname: Strauss
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Streicher
authors.forename: Madelene
authors.initials: M
authors.lastname: Hanekom
authors.forename: Thelma
authors.initials: T
authors.lastname: Liversage
authors.forename: Mothusi
authors.initials: M
authors.lastname: Masibi
authors.forename: Paul D
authors.initials: PD
authors.lastname: van Helden
authors.forename: Robin M
authors.initials: RM
authors.lastname: Warren
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Victor
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use; D021821:Communicable Diseases, Emerging / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology*; D016358:Contact Tracing; D023801:Directly Observed Therapy; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D055118:Medication Adherence; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D010802:Phylogeny; D011718:Pyrazinamide / Q000627:therapeutic use; D013019:South Africa / Q000453:epidemiology
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide