title: Beijing and Haarlem genotypes are overrepresented among children with drug-resistant tuberculosis in the Western Cape Province of South Africa.
abstract: Drug resistance among children with culture-confirmed tuberculosis (TB) provides an accurate measure of transmitted drug resistance within the community. We describe the genotype diversity in children with culture-confirmed TB and investigate the relationship between genotype and drug resistance. A prospective study was conducted from March 2003 through August 2005 at Tygerberg Children's Hospital, in the Western Cape Province of South Africa. All children (<13 years of age) diagnosed with culture-confirmed TB were included. Genotype analysis and phenotypic drug susceptibility testing were performed on the first culture-positive isolate from each patient. Mutation analysis was performed on all drug-resistant isolates. Spoligotyping was successfully performed on isolates from 391/399 (98%) children diagnosed with culture-confirmed TB. Drug susceptibility testing was also performed on 391 isolates; 49 (12.5%) were resistant to isoniazid, and 20 (5.1%) of these were resistant to both isoniazid and rifampin. Beijing was the most common genotype family, identified in 130/391 (33.2%) cases, followed by LAM in 114/391 (29.2%) cases. The presence of both Beijing and Haarlem genotype families was significantly associated with drug resistance (26/49 [53.1%] versus 113/342 [33.0%]; odds ratio, 1.7; 95% confidence interval, 1.0 to 2.9). The high prevalence of Beijing and LAM in children with culture-confirmed TB reflects considerable transmission of these genotype families within the community. The overrepresentation of Beijing and Haarlem genotype families in children with drug-resistant TB demonstrates their contribution to transmitted drug resistance and their potential importance in the emergent drug-resistant TB epidemic.
authors.affiliation: Ukwanda Centre for Rural Health, Faculty of Health Sciences, Stellenbosch University, P.O. Box 19063, Tygerberg 7505, South Africa. bjmarais@sun.ac.za
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Marais
authors.forename: Tommie C
authors.initials: TC
authors.lastname: Victor
authors.forename: Anneke C
authors.initials: AC
authors.lastname: Hesseling
authors.forename: Madeleine
authors.initials: M
authors.lastname: Barnard
authors.forename: Annemie
authors.initials: A
authors.lastname: Jordaan
authors.forename: Wendy
authors.initials: W
authors.lastname: Brittle
authors.forename: Helmuth
authors.initials: H
authors.lastname: Reuter
authors.forename: Nulda
authors.initials: N
authors.lastname: Beyers
authors.forename: Paul D
authors.initials: PD
authors.lastname: van Helden
authors.forename: Rob M
authors.initials: RM
authors.lastname: Warren
authors.forename: H Simon
authors.initials: HS
authors.lastname: Schaaf
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics; D013019:South Africa / Q000453:epidemiology; D014376:Tuberculosis / Q000188:drug therapy* / Q000453:epidemiology*
chemical_list: D000995:Antitubercular Agents