Abstract
ObjectivesTo characterize the clonal complexity in Mycobacterium tuberculosis (MTB) infections considering factors that help maximize the detection of coexisting strains/variants. MethodsGenotypic 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. ResultsGenotypic 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. ConclusionsDirect 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.
Highlights
Molecular and genomic approaches have weakened the assumption that Mycobacterium tuberculosis (MTB) infections are clonally homogeneous
To characterize the clonal complexity in Mycobacterium tuberculosis (MTB) infections considering factors that help maximize the detection of coexisting strains/variants
Direct MTB genotyping from post-mortem tissue samples revealed a frequent within-host
Summary
Molecular and genomic approaches have weakened the assumption that Mycobacterium tuberculosis (MTB) infections are clonally homogeneous. In most studies cultures were analysed (which may distort specimen complexity [4,5]), extensive sampling was not assured, the studies focused on respiratory specimens, or were performed in settings with low tuberculosis (TB) incidence. The aim of this study was to characterize the clonal complexity in TB by aiming to maximize its detection. We focused on a setting with a high burden of TB (Southern Mozambique), where the risk of overexposure is higher, and included patients with a post-mortem diagnosis of TB, candidates of prolonged disease in whom microevolution events might have occurred. An exhaustive sampling was assured and analyses were done directly on biopsies to exclude any impact of cultured samples
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