title: Mycobacterium tuberculosis lineage 7 strains are associated with prolonged patient delay in seeking treatment for pulmonary tuberculosis in Amhara Region, Ethiopia.
abstract: Recent genotyping studies of Mycobacterium tuberculosis in Ethiopia have reported the identification of a new phylogenetically distinct M. tuberculosis lineage, lineage 7. We therefore investigated the genetic diversity and association of specific M. tuberculosis lineages with sociodemographic and clinical parameters among pulmonary TB patients in the Amhara Region, Ethiopia. DNA was isolated from M. tuberculosis-positive sputum specimens (n=240) and analyzed by PCR and 24-locus mycobacterial interspersed repetitive unit-variable-number tandem-repeat (MIRU-VNTR) analysis and spoligotyping. Bioinformatic analysis assigned the M. tuberculosis genotypes to global lineages, and associations between patient characteristics and genotype were evaluated using logistic regression analysis. The study revealed a high diversity of modern and premodern M. tuberculosis lineages, among which approximately 25% were not previously reported. Among the M. tuberculosis strains (n=138) assigned to seven subgroups, the largest cluster belonged to the lineage Central Asian (CAS) (n=60; 26.0%), the second largest to lineage 7 (n=36; 15.6%), and the third largest to the lineage Haarlem (n=35; 15.2%). Four sublineages were new in the MIRU-VNTRplus database, designated NW-ETH3, NW-ETH1, NW-ETH2, and NW-ETH4, which included 24 (10.4%), 18 (7.8%), 8 (3.5%), and 5 (2.2%) isolates, respectively. Notably, patient delay in seeking treatment was significantly longer among patients infected with lineage 7 strains (Mann-Whitney test, P<0.008) than in patients infected with CAS strains (adjusted odds ratio [AOR], 4.7; 95% confidence interval [CI], 1.6 to 13.5). Lineage 7 strains also grew more slowly than other M. tuberculosis strains. Cases of Haarlem (OR, 2.8; 95% CI, 1.2 to 6.6) and NW-ETH3 (OR, 2.8; 95% CI, 1.0 to 7.3) infection appeared in defined clusters. Intensified active case finding and contact tracing activities in the study region are needed to expedite diagnosis and treatment of TB.
authors: Department of Microbiology, Unit for Genome Dynamics, Oslo University Hospital, Nydalen, Oslo, Norway Department of Bacteriology and Immunology, Norwegian Institute of Public Health, Division of Infectious Disease Control, Nydalen, Oslo, Norway Institute of Health and Society, Section for International Health, Faculty of Medicine, University of Oslo, Blindern, Oslo, Norway Amhara Regional State Health Bureau, Bahir Dar, Bahir Dar, Ethiopia s.a.yimer@medisin.uio.no.
authors: Solomon A
authors: SA
authors: Yimer
authors: Department of Bacteriology and Immunology, Norwegian Institute of Public Health, Division of Infectious Disease Control, Nydalen, Oslo, Norway.
authors: Gunnstein
authors: G
authors: Norheim
authors: Department of Microbiology, Unit for Genome Dynamics, Oslo University Hospital, Nydalen, Oslo, Norway.
authors: Amine
authors: A
authors: Namouchi
authors: Department of Microbiology, Unit for Genome Dynamics, Oslo University Hospital, Nydalen, Oslo, Norway.
authors: Ephrem D
authors: ED
authors: Zegeye
authors: Department of Bacteriology and Immunology, Norwegian Institute of Public Health, Division of Infectious Disease Control, Nydalen, Oslo, Norway.
authors: Wibeke
authors: W
authors: Kinander
authors: Department of Microbiology, Unit for Genome Dynamics, Oslo University Hospital, Nydalen, Oslo, Norway Department of Microbiology, Unit for Genome Dynamics, University of Oslo, Oslo, Norway.
authors: Tone
authors: T
authors: Tønjum
authors: Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
authors: Shiferaw
authors: S
authors: Bekele
authors: Department of Bacteriology and Immunology, Norwegian Institute of Public Health, Division of Infectious Disease Control, Nydalen, Oslo, Norway.
authors: Turid
authors: T
authors: Mannsåker
authors: Institute of Health and Society, Section for International Health, Faculty of Medicine, University of Oslo, Blindern, Oslo, Norway.
authors: Gunnar
authors: G
authors: Bjune
authors: Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
authors: Abraham
authors: A
authors: Aseffa
authors: Department of Bacteriology and Immunology, Norwegian Institute of Public Health, Division of Infectious Disease Control, Nydalen, Oslo, Norway.
authors: Carol
authors: C
authors: Holm-Hansen
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D057210:Delayed Diagnosis; D005002:Ethiopia / Q000453:epidemiology; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D017720:Molecular Epidemiology; D058889:Molecular Typing; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification*; D013183:Sputum / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000453:epidemiology / Q000382:microbiology*; D014774:Virulence
chemical_list: D004269:DNA, Bacterial