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Updated: Nov 2, 2025

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Published on: June 6, 2025
High within-host diversity found from direct genotyping on post-mortem tuberculosis specimens in a high-burden
Cristina Rodríguez-Grande1, Juan Carlos Hurtado2, Sandra Rodríguez-Maus1
1Servicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
Directly analyzing post-mortem tissues revealed frequent within-host Mycobacterium tuberculosis (MTB) diversity, including mixed infections. This highlights the importance of examining multiple tissues to fully understand tuberculosis clonal complexity.
Area of Science:
- Microbiology
- Genetics
- Infectious Diseases
Background:
- Tuberculosis remains a global health challenge, particularly in high-burden countries like Mozambique.
- Understanding Mycobacterium tuberculosis (MTB) clonal complexity is crucial for effective disease control.
- Standard diagnostic methods may underestimate within-host diversity.
Purpose of the Study:
- To characterize the clonal complexity of MTB infections.
- To identify factors that maximize the detection of coexisting MTB strains or variants.
- To assess within-patient diversity using direct genotyping from multiple post-mortem tissues.
Main Methods:
- Genotypic analysis using Mycobacterial Interspersed Repetitive-Unit-Variable-Number Tandem-Repeats (MIRU-VNTR).
- Direct analysis of 70 biopsy specimens from 28 post-mortem tuberculosis cases.
- Inclusion of samples from two or more different tissues per case.
Main Results:
- Genotypic data were obtained for 82.1% of cases, enabling within-patient diversity analysis.
- MIRU-VNTR revealed clonal diversity in 35.7% of cases.
- Five cases showed mixed infections with distinct MTB strains, with brain tissue frequently associated with heterogeneity.
Conclusions:
- Direct MTB genotyping from post-mortem tissues frequently reveals within-host diversity, including mixed and polyclonal infections.
- Standard analysis of respiratory specimens alone likely overlooks significant MTB diversity.
- Comprehensive tissue sampling is essential for accurate assessment of MTB clonal complexity.
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