Tuberculous Lymphadenitis in Ethiopia Predominantly Caused by Strains Belonging to the Delhi/CAS Lineage and Newly Identified Ethiopian Clades of the Mycobacterium tuberculosis Complex

PLoS One. 2015 Sep 16;10(9):e0137865. doi: 10.1371/journal.pone.0137865. eCollection 2015.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Bacterial Typing Techniques
  • Child
  • Child, Preschool
  • DNA, Bacterial / genetics
  • Ethiopia / epidemiology
  • Female
  • Genetic Variation / genetics
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Minisatellite Repeats / genetics
  • Molecular Epidemiology*
  • Mycobacterium tuberculosis / classification*
  • Mycobacterium tuberculosis / isolation & purification*
  • Phylogeny
  • Tuberculosis, Lymph Node / epidemiology*
  • Tuberculosis, Lymph Node / microbiology
  • Tuberculosis, Lymph Node / transmission*
  • Young Adult

Substances

  • DNA, Bacterial

Grants and funding

The work presented in this paper was made possible by funding from the German Federal Ministry of Education and Research (BMBF, 1315883), the Institute of Medical Microbiology and Epidemiology of Infectious Diseases, Institute of clinical immunology, University Hospital Leipzig, Germany, Translational Centre for Regenerative Medicine (TRM), University Hospital Leipzig, Germany, Molecular Mycobacteriology, Research Center Borstel, Germany, the German Academic Exchange Service (DAAD) and University of Bahir Dar, Ethiopia. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.