High within-host diversity found from direct genotyping on post-mortem tuberculosis specimens in a high-burden setting

Clin Microbiol Infect. 2021 Oct;27(10):1518.e5-1518.e9. doi: 10.1016/j.cmi.2021.05.038. Epub 2021 Jun 11.

Abstract

Objectives: To characterize the clonal complexity in Mycobacterium tuberculosis (MTB) infections considering factors that help maximize the detection of coexisting strains/variants.

Methods: Genotypic analysis by Mycobacterial Interspersed Repetitive-Unit-Variable-Number Tandem-Repeats (MIRU-VNTR) was performed directly on 70 biopsy specimens from two or more different tissues involving 28 tuberculosis cases diagnosed post-mortem in Mozambique, a country with a high tuberculosis burden.

Results: Genotypic data from isolates collected from two or more tissues were obtained for 23 of the 28 cases (82.1%), allowing the analysis of within-patient diversity. MIRU-VNTR analysis revealed clonal diversity in ten cases (35.7%). Five cases showed allelic differences in three or more loci, suggesting mixed infection with two different strains. In half of the cases showing within-host diversity, one of the specimens associated with clonal heterogeneity was brain tissue.

Conclusions: Direct MTB genotyping from post-mortem tissue samples revealed a frequent within-host Mycobacterium tuberculosis diversity, including mixed and polyclonal infections. Most of this diversity would have been overlooked if only standard analysis of respiratory specimens had been performed.

Keywords: Clonal complexity; Genotyping; Mozambique; Post-mortem; Tuberculosis.

MeSH terms

  • Alleles
  • Autopsy
  • Genotype
  • Humans
  • Minisatellite Repeats
  • Mozambique / epidemiology
  • Mycobacterium tuberculosis* / genetics
  • Tuberculosis* / epidemiology
  • Tuberculosis* / microbiology