title: Strain-specific estimation of epidemic success provides insights into the transmission dynamics of tuberculosis.
abstract: The transmission dynamics of tuberculosis involves complex interactions of socio-economic and, possibly, microbiological factors. We describe an analytical framework to infer factors of epidemic success based on the joint analysis of epidemiological, clinical and pathogen genetic data. We derive isolate-specific, genetic distance-based estimates of epidemic success, and we represent success-related time-dependent concepts, namely epidemicity and endemicity, by restricting analysis to specific time scales. The method is applied to analyze a surveillance-based cohort of 1,641 tuberculosis patients with minisatellite-based isolate genotypes. Known predictors of isolate endemicity (older age, native status) and epidemicity (younger age, sputum smear positivity) were identified with high confidence (P < 0.001). Long-term epidemic success also correlated with the ability of Euro-American and Beijing MTBC lineages to cause active pulmonary infection, independent of patient age and country of origin. Our results demonstrate how important insights into the transmission dynamics of tuberculosis can be gained from active surveillance data.
authors.affiliation: Institut de Systématique, Evolution, Biodiversité, UMR-CNRS 7205, Muséum National d'Histoire Naturelle, Université Pierre et Marie Curie, Ecole Pratique des Hautes Etudes, Sorbonne Universités, Paris, France.|Laboratoire Biologie Intégrative des Populations, Ecole Pratique des Hautes Etudes, PSL Research University, Paris, France.|Centre International de Recherche en Infectiologie, CIRI, University of Lyon, France.|Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Rasigade
authors.affiliation: Institut de Systématique, Evolution, Biodiversité, UMR-CNRS 7205, Muséum National d'Histoire Naturelle, Université Pierre et Marie Curie, Ecole Pratique des Hautes Etudes, Sorbonne Universités, Paris, France.|Laboratoire Biologie Intégrative des Populations, Ecole Pratique des Hautes Etudes, PSL Research University, Paris, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Barbier
authors.affiliation: Centre International de Recherche en Infectiologie, CIRI, University of Lyon, France.|Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France.
authors.forename: Oana
authors.initials: O
authors.lastname: Dumitrescu
authors.affiliation: Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Pichat
authors.affiliation: Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Carret
authors.affiliation: Comité Départemental d'Hygiène Sociale, CLAT69, Lyon, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Ronnaux-Baron
authors.affiliation: Comité Départemental d'Hygiène Sociale, CLAT69, Lyon, France.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Blasquez
authors.affiliation: Agence Régionale de Santé Rhône-Alpes, Lyon, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Godin-Benhaim
authors.affiliation: Laboratoire de Bactériologie, Institut de Biologie et de Pathologie, CHU de Grenoble, Grenoble, France.|Laboratoire TIMC-IMAG, UMR 5525 CNRS-UJF, UFR de Médecine, Université Grenoble Alpes, Grenoble, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Boisset
authors.affiliation: Laboratoire des Agents Infectieux et d'Hygiène, CHU de Saint-Etienne, Saint-Etienne, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Carricajo
authors.affiliation: Laboratoire Biomnis, Lyon, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Jacomo
authors.affiliation: Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fredenucci
authors.affiliation: Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Pérouse de Montclos
authors.affiliation: Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France.|Laboratoire de Biométrie et Biologie Evolutive, UMR CNRS 5558, University of Lyon, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Flandrois
authors.affiliation: Centre International de Recherche en Infectiologie, CIRI, University of Lyon, France.|Service des Maladies Infectieuses et Tropicales, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Ader
authors.affiliation: INSERM U1019, CNRS-UMR 8204, Center for Infection and Immunity of Lille, Institut Pasteur de Lille, Université de Lille, Lille, France.
authors.forename: Philip
authors.initials: P
authors.lastname: Supply
authors.affiliation: Centre International de Recherche en Infectiologie, CIRI, University of Lyon, France.|Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Lina
authors.affiliation: Institut de Systématique, Evolution, Biodiversité, UMR-CNRS 7205, Muséum National d'Histoire Naturelle, Université Pierre et Marie Curie, Ecole Pratique des Hautes Etudes, Sorbonne Universités, Paris, France.|Laboratoire Biologie Intégrative des Populations, Ecole Pratique des Hautes Etudes, PSL Research University, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Wirth
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000302:isolation & purification; D012307:Risk Factors; D013183:Sputum / Q000382:microbiology; D014376:Tuberculosis / Q000453:epidemiology / Q000382:microbiology / Q000473:pathology* / Q000635:transmission