title: Tuberculous Lymphadenitis in Ethiopia Predominantly Caused by Strains Belonging to the Delhi/CAS Lineage and Newly Identified Ethiopian Clades of the Mycobacterium tuberculosis Complex.
abstract: BACKGROUND
  Recently, newly defined clades of Mycobacterium tuberculosis complex (MTBC) strains, namely Ethiopia 1-3 and Ethiopia H37Rv-like strains, and other clades associated with pulmonary TB (PTB) were identified in Ethiopia. In this study, we investigated whether these new strain types exhibit an increased ability to cause TB lymphadenitis (TBLN) and raised the question, if particular MTBC strains derived from TBLN patients in northern Ethiopia are genetically adapted to their local hosts and/or to the TBLN.
  
  
  METHODS
  Genotyping of 196 MTBC strains isolated from TBLN patients was performed by spoligotyping and 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) typing. A statistical analysis was carried out to see possible associations between patient characteristics and phylogenetic MTBC strain classification.
  
  
  RESULTS
  Among 196 isolates, the majority of strains belonged to the Delhi/CAS (38.8%) lineage, followed by Ethiopia 1 (9.7%), Ethiopia 3 (8.7%), Ethiopia H37RV-like (8.2%), Ethiopia 2 and Haarlem (7.7% each), URAL (3.6%), Uganda l and LAM (2% each), S-type (1.5%), X-type (1%), and 0.5% isolates of TUR, EAI, and Beijing genotype, respectively. Overall, 15 strains (7.7%) could not be allocated to a previously described phylogenetic lineage. The distribution of MTBC lineages is similar to that found in studies of PTB samples. The cluster rate (35%) in this study is significantly lower (P = 0.035) compared to 45% in the study of PTB in northwestern Ethiopia.
  
  
  CONCLUSIONS
  In the studied area, lymph node samples are dominated by Dehli/CAS genotype strains and strains of largely not yet defined clades based on MIRU-VNTR 24-loci nomenclature. We found no indication that strains of particular genotypes are specifically associated with TBLN. However, a detailed analysis of specific genetic variants of the locally contained Ethiopian clades by whole genome sequencing may reveal new insights into the host-pathogen co-evolution and specific features that are related to the local host immune system.
authors.affiliation: College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia; Institute of Medical Microbiology and Epidemiology of Infectious Diseases, University Hospital, University of Leipzig, Leipzig, Germany; Institute of Clinical Immunology, University Hospital, University of Leipzig, Leipzig, Germany; Translational Centre for Regenerative Medicine (TRM)-Leipzig, University of Leipzig, Leipzig, Germany.
authors.forename: Fantahun
authors.initials: F
authors.lastname: Biadglegne
authors.affiliation: Molecular Mycobacteriology, Research Center Borstel, Borstel, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Merker
authors.affiliation: Institute of Clinical Immunology, University Hospital, University of Leipzig, Leipzig, Germany; Translational Centre for Regenerative Medicine (TRM)-Leipzig, University of Leipzig, Leipzig, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sack
authors.affiliation: Institute of Medical Microbiology and Epidemiology of Infectious Diseases, University Hospital, University of Leipzig, Leipzig, Germany.
authors.forename: Arne C
authors.initials: AC
authors.lastname: Rodloff
authors.affiliation: Molecular Mycobacteriology, Research Center Borstel, Borstel, Germany; German Center for Infection Research, Partner Site Borstel, Borstel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Niemann
mesh_terms: D000293:Adolescent; D000328:Adult; D015373:Bacterial Typing Techniques; D002648:Child; D002675:Child, Preschool; D004269:DNA, Bacterial / Q000235:genetics; D005002:Ethiopia / Q000453:epidemiology; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D017720:Molecular Epidemiology; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000302:isolation & purification*; D010802:Phylogeny; D014388:Tuberculosis, Lymph Node / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission*; D055815:Young Adult
chemical_list: D004269:DNA, Bacterial