title: Changing Mycobacterium tuberculosis population highlights clade-specific pathogenic characteristics.
abstract: Mycobacterium tuberculosis strains can be classified into a number of major clades according to defined evolutionary markers. It is hypothesised that strains comprising these clades have evolved different properties which may influence a local strain population structure. To investigate this, we analysed the incidence of tuberculosis caused by the predominant clades (Beijing, Haarlem, LAM, Quebec and the Low-Copy Clade) found in a community within the Cape Town metropole in South Africa over a 12-year period. We found that while the incidence of cases infected with strains of the Haarlem, LAM, Quebec and the Low-Copy Clades remained relatively stable, that of cases of the Beijing clade increased exponentially over time, with a doubling time of 4.86 years (P=0.018). This growth was exclusively attributable to drug-susceptible strains. Although drug-resistant Beijing cases remained constant in number, non-Beijing drug-resistant cases declined over time (P=0.007). Drug-susceptible Beijing-infected cases had a greater proportion of smear-positive sputa than their non-Beijing counterparts (P=0.013) and were less likely to be successfully treated (retreatment cases) (P=0.026). Recent evidence suggests that these differences likely reflect enhanced pathogenicity rather than transmissibility. The rapid emergence of Beijing strains demonstrates adaptation to conditions within the study community and poses a grave challenge to future TB control.
authors.affiliation: Division of Molecular Biology and Human Genetics, Faculty of Health Sciences, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research/MRC Centre for Molecular and Cellular Biology, Stellenbosch University, Tygerberg, South Africa. gvds@sun.ac.za
authors.forename: G D
authors.initials: GD
authors.lastname: van der Spuy
authors.forename: K
authors.initials: K
authors.lastname: Kremer
authors.forename: S L
authors.initials: SL
authors.lastname: Ndabambi
authors.forename: N
authors.initials: N
authors.lastname: Beyers
authors.forename: R
authors.initials: R
authors.lastname: Dunbar
authors.forename: B J
authors.initials: BJ
authors.lastname: Marais
authors.forename: P D
authors.initials: PD
authors.lastname: van Helden
authors.forename: R M
authors.initials: RM
authors.lastname: Warren
mesh_terms: D000328:Adult; D015373:Bacterial Typing Techniques; D016172:DNA Fingerprinting / Q000379:methods; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D012150:Polymorphism, Restriction Fragment Length; D013019:South Africa / Q000453:epidemiology; D013183:Sputum / Q000382:microbiology; D014376:Tuberculosis / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology*; D014774:Virulence / Q000235:genetics
chemical_list: D004269:DNA, Bacterial