title: Geography and genealogy of the human host harbouring a distinctive drug-resistant strain of tuberculosis.
abstract: For a strain of Mycobacterium tuberculosis mono-resistant to pyrazinamide (PZA), we report the geographic distribution within Quebec of the 77 cases diagnosed during 1990-2000. Known as the Quebec mutation (or the pncA deletion), the strain is rare in urban areas and showed an unexpected concentration in Mauricie, one of the 16 health districts of the province, with a cluster of 10 cases situated in a rural area of 35-km radius. The cases occurred among people >50 (98%), of French Canadian origins (90%), and are understood to have arisen by reactivation. The rarity in Montreal and smaller cities is explained by the youthfulness of massive postwar migrations. To reach back into the history of settlement, we examined genealogies: 92,429 ancestral marriages for 32 of the 77 PZA-resistant isolates and 226,535 for a set of 85 controls with isolates of more diverse mycobacterial strains. Genealogical analysis showed no salient common ancestor for the cases, and kinship among them was no greater than observed in control samples from the same regions. But it identified an unsuspected geographical region as the site of ancestral concentrations prior to 1840, for both resistant strains and controls. The following scenario is proposed for the resistant strain: endemic in a specific geographical region by 1800, it dispersed with families moving into regions opened to settlement in the 1840s and 1850s, among them Mauricie, where dispersion was intensified by seasonal mobility of labour in logging, milling and marketing timber. In high-incidence areas, it is difficult to distinguish cases of reactivation from recent infections, but the low-incidence context allows us to observe a 200-year trajectory of a distinctive drug-resistant strain of M. tuberculosis.
authors.affiliation: Department of Medicine, McGill University Health Center, Royal Victoria Hospital, Montréal, Québec, Canada H3A 1A1. paul.brassard@clinepi.mcgill.ca
authors.forename: Paul
authors.initials: P
authors.lastname: Brassard
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Henry
authors.forename: Kevin
authors.initials: K
authors.lastname: Schwartzman
authors.forename: Michèle
authors.initials: M
authors.lastname: Jomphe
authors.forename: Sherry H
authors.initials: SH
authors.lastname: Olson
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use; D003241:Consanguinity; D003710:Demography; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005843:Geography; D054884:Host-Pathogen Interactions / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D015994:Incidence; D010802:Phylogeny; D011718:Pyrazinamide / Q000627:therapeutic use; D011792:Quebec / Q000453:epidemiology; D012042:Registries; D014376:Tuberculosis / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide