title: Mycobacterium tuberculosis lineages and anti-tuberculosis drug resistance in reference hospitals across Viet Nam.
abstract: Mycobacterium tuberculosis, the tuberculosis (TB) pathogen, despite a low level of genetic diversity, has revealed a high variety of biological and epidemiological characteristics linked to their lineages, such as transmissibility, fitness and propensity to acquire drug resistance. This has important implications for the epidemiology of TB. We conducted this first countrywide cross-sectional study to identify the prevalent M. tuberculosis lineages and to assess their epidemiological associations and their relation to drug resistance. The study was conducted among isolates acquired in reference hospitals across Vietnam. Isolates with drug susceptibility testing profiles were identified for their lineages by spoligotyping. Logistic regression was used to investigate the association of M. tuberculosis lineages with location, age and sex of the patients and drug resistance levels.
  
  
  
  Results showed that the most prevalent lineage was Beijing (55.4 %), followed by EAI (27.5 %), T (6.4 %), LAM (1.3 %), Haarlem (1 %) and Zero type (0.3 %). The proportion of Beijing isolates in the North (70.4 %) and the South (68 %) was higher than in the Centre (28 %) (OR = 1.7 [95 % CI: 1.4-2.0], p < 0.0001), whereas the proportion of EAI isolates in the North (7.1 %) and the South (17 %) was much lower compared with the Centre (59 %) (OR = 0.5 [95 % CI: 0.4-0.6], p < 0.0001). Overall, Beijing isolates were the most likely to be drug-resistant and EAI isolates were the least likely to be drug-resistant, except in the South of Vietnam where EAI is also highly drug-resistant. The proportion of Beijing isolates was significantly higher (p < 0.01), and the proportion of EAI isolates was significantly lower (p < 0.05) in younger patients. The proportion of drug-resistance was higher in isolates collected from male patients and from patients in the middle age groups.
  
  
  
  The findings suggest ongoing replacement of EAI lineage, which is mainly more drug-susceptible with highly drug-resistant Beijing lineage in all studied regions of Vietnam. Male patients of working ages should be the focus for better control to prevent the emergence of drug-resistant TB.
authors.affiliation: Department of Bacteriology, National Institute of Hygiene Epidemiology, Hanoi, Vietnam. vananhtdt@gmail.com.|Laboratory of Tuberculosis, Department of Bacteriology, National Institute of Hygiene and Epidemiology, Hanoi, 10000, Vietnam. vananhtdt@gmail.com.
authors.forename: Van Anh Thi
authors.initials: VA
authors.lastname: Nguyen
authors.affiliation: Department of Bacteriology, National Institute of Hygiene Epidemiology, Hanoi, Vietnam.|MIVEGEC (IRD 224-CNRS 5290-Université de Montpellier), Centre IRD, Montpellier, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Bañuls
authors.affiliation: Department of Bacteriology, National Institute of Hygiene Epidemiology, Hanoi, Vietnam.
authors.forename: Thanh Hoa Thi
authors.initials: TH
authors.lastname: Tran
authors.affiliation: Department of Bacteriology, National Institute of Hygiene Epidemiology, Hanoi, Vietnam.
authors.forename: Kim Lien Thi
authors.initials: KL
authors.lastname: Pham
authors.affiliation: Department of Microbiology, Hospital 103, Military Medical University, Hanoi, Vietnam.
authors.forename: Thai Son
authors.initials: TS
authors.lastname: Nguyen
authors.affiliation: Department of Microbiology, National Lung Hospital, Hanoi, Vietnam.
authors.forename: Hung Van
authors.initials: HV
authors.lastname: Nguyen
authors.affiliation: Department of Microbiology, Pham Ngoc Thach Hospital, Ho Chi Minh city, Vietnam.
authors.forename: Ngoc Lan Thi
authors.initials: NL
authors.lastname: Nguyen
authors.affiliation: Department of Microbiology, Hue Central Hospital, Hue, Vietnam.
authors.forename: Nam Lien Thi
authors.initials: NL
authors.lastname: Nguyen
authors.affiliation: Department of Bacteriology, National Institute of Hygiene Epidemiology, Hanoi, Vietnam.
authors.forename: Duc Anh
authors.initials: DA
authors.lastname: Dang
authors.affiliation: Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia.|South Western Sydney Clinical School, UNSW, Sydney, Australia.
authors.forename: Guy B
authors.initials: GB
authors.lastname: Marks
authors.affiliation: MIVEGEC (IRD 224-CNRS 5290-Université de Montpellier), Centre IRD, Montpellier, France.|Oxford University Clinical Research Unit, Hanoi, Vietnam.
authors.forename: Marc
authors.initials: M
authors.lastname: Choisy
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006761:Hospitals; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D017720:Molecular Epidemiology; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D010802:Phylogeny; D012737:Sex Factors; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology / Q000382:microbiology*; D014744:Vietnam / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D004269:DNA, Bacterial
keywords: Drug resistance; Lineage; Mycobacterium tuberculosis; Reference hospital; Tuberculosis; Vietnam