title: HIV infection disrupts the sympatric host-pathogen relationship in human tuberculosis.
abstract: The phylogeographic population structure of Mycobacterium tuberculosis suggests local adaptation to sympatric human populations. We hypothesized that HIV infection, which induces immunodeficiency, will alter the sympatric relationship between M. tuberculosis and its human host. To test this hypothesis, we performed a nine-year nation-wide molecular-epidemiological study of HIV-infected and HIV-negative patients with tuberculosis (TB) between 2000 and 2008 in Switzerland. We analyzed 518 TB patients of whom 112 (21.6%) were HIV-infected and 233 (45.0%) were born in Europe. We found that among European-born TB patients, recent transmission was more likely to occur in sympatric compared to allopatric host-pathogen combinations (adjusted odds ratio [OR] 7.5, 95% confidence interval [95% CI] 1.21-infinity, p = 0.03). HIV infection was significantly associated with TB caused by an allopatric (as opposed to sympatric) M. tuberculosis lineage (OR 7.0, 95% CI 2.5-19.1, p<0.0001). This association remained when adjusting for frequent travelling, contact with foreigners, age, sex, and country of birth (adjusted OR 5.6, 95% CI 1.5-20.8, p = 0.01). Moreover, it became stronger with greater immunosuppression as defined by CD4 T-cell depletion and was not the result of increased social mixing in HIV-infected patients. Our observation was replicated in a second independent panel of 440 M. tuberculosis strains collected during a population-based study in the Canton of Bern between 1991 and 2011. In summary, these findings support a model for TB in which the stable relationship between the human host and its locally adapted M. tuberculosis is disrupted by HIV infection.
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Fenner
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
authors.forename: Thomas
authors.initials: T
authors.lastname: Bodmer
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Marie
authors.initials: M
authors.lastname: Ballif
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.forename: Peter
authors.initials: P
authors.lastname: Helbling
authors.forename: Jan
authors.initials: J
authors.lastname: Fehr
authors.forename: Thomas
authors.initials: T
authors.lastname: Gsponer
authors.forename: Hans L
authors.initials: HL
authors.lastname: Rieder
authors.forename: Marcel
authors.initials: M
authors.lastname: Zwahlen
authors.forename: Matthias
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.forename: Alexandra
authors.initials: A
authors.lastname: Calmy
authors.forename: Marisa
authors.initials: M
authors.lastname: Dolina
authors.forename: Reno
authors.initials: R
authors.lastname: Frei
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Janssens
authors.forename: Sonia
authors.initials: S
authors.lastname: Borrell
authors.forename: David
authors.initials: D
authors.lastname: Stucki
authors.forename: Jacques
authors.initials: J
authors.lastname: Schrenzel
authors.forename: Erik C
authors.initials: EC
authors.lastname: Böttger
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gagneux
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes; D019143:Evolution, Molecular; D005260:Female; D006678:HIV / Q000472:pathogenicity; D015658:HIV Infections / Q000150:complications / Q000235:genetics / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D058974:Phylogeography; D013557:Switzerland; D061350:Sympatry; D014376:Tuberculosis / Q000150:complications / Q000235:genetics / Q000382:microbiology