title: Transmission and Progression to Disease of Mycobacterium tuberculosis Phylogenetic Lineages in The Netherlands.
abstract: The aim of this study was to determine if mycobacterial lineages affect infection risk, clustering, and disease progression among Mycobacterium tuberculosis cases in The Netherlands. Multivariate negative binomial regression models adjusted for patient-related factors and stratified by patient ethnicity were used to determine the association between phylogenetic lineages and infectivity (mean number of positive contacts around each patient) and clustering (as defined by number of secondary cases within 2 years after diagnosis of an index case sharing the same fingerprint) indices. An estimate of progression to disease by each risk factor was calculated as a bootstrapped risk ratio of the clustering index by the infectivity index. Compared to the Euro-American reference, Mycobacterium africanum showed significantly lower infectivity and clustering indices in the foreign-born population, while Mycobacterium bovis showed significantly lower infectivity and clustering indices in the native population. Significantly lower infectivity was also observed for the East African Indian lineage in the foreign-born population. Smear positivity was a significant risk factor for increased infectivity and increased clustering. Estimates of progression to disease were significantly associated with age, sputum-smear status, and behavioral risk factors, such as alcohol and intravenous drug abuse, but not with phylogenetic lineages. In conclusion, we found evidence of a bacteriological factor influencing indicators of a strain's transmissibility, namely, a decreased ability to infect and a lower clustering index in ancient phylogenetic lineages compared to their modern counterparts. Confirmation of these findings via follow-up studies using tuberculin skin test conversion data should have important implications on M. tuberculosis control efforts.
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal ICVS/3Bs, PT Government Associate Laboratory, Braga/Guimarães, Portugal hanna.guimaraes@gmail.com.
authors.forename: Hanna
authors.initials: H
authors.lastname: Nebenzahl-Guimaraes
authors.affiliation: Wilhelmina Children's Hospital Utrecht, Utrecht, The Netherlands Laboratory of Pediatric Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Lilly M
authors.initials: LM
authors.lastname: Verhagen
authors.affiliation: Public Health Service, Amsterdam, The Netherlands Department of Clinical Epidemiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Martien W
authors.initials: MW
authors.lastname: Borgdorff
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: van Soolingen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D016172:DNA Fingerprinting; D018450:Disease Progression; D018562:Disease Transmission, Infectious; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D009161:Mycobacterium / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D009426:Netherlands / Q000453:epidemiology; D010802:Phylogeny; D018570:Risk Assessment; D014376:Tuberculosis / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission*; D055815:Young Adult