Abstract
BackgroundThere is increasing evidence to suggest that different Mycobacterium tuberculosis lineages cause variations in the clinical presentation of tuberculosis (TB). Certain M. tuberculosis genotypes/lineages have been shown to be more likely to cause active TB in human populations from a distinct genetic ancestry. This study describes the genetic biodiversity of M. tuberculosis genotypes in Mwanza city, Tanzania and the clinical presentation of the disease caused by isolates of different lineages.MethodsTwo-hundred-fifty-two isolates from pulmonary TB patients in Mwanza, Tanzania were characterized by spoligotyping, and 45 isolates were further characterized by mycobacterium interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR). The patients’ level of the acute phase reactants AGP, CRP and neutrophil counts, in addition to BMI, were measured and compared to the M. tuberculosis lineage of the infectious agent for each patient.ResultsThe most frequent genotype was ST59 (48 out of 248 [19.4%]), belonging to the Euro-American lineage LAM11_ZWE, followed by ST21 (CAS_KILI lineage [44 out of 248 [17.7%]). A low degree of diversity (15.7% [39 different ST’s out of 248 isolates]) of genotypes, in addition to a high level of mixed M. tuberculosis sub-populations among isolates with an unreported spoligotype pattern (10 out of 20 isolates [50.0%]) and isolates belonging to the ST53 lineage (13 out of 25 [52%]) was observed. Isolates of the ‘modern’ (TbD1-) Euro-American lineage induced higher levels of α1-acid glycoprotein (β = 0.4, P = 0.02; 95% CI [0.06-0.66]) and neutrophil counts (β = 0.9, P = 0.02; 95% CI [0.12-1.64]) and had lower BMI score (β = -1.0, P = 0.04; 95% CI[-1.89 – (-0.03)]). LAM11_ZWE (‘modern’) isolates induced higher levels of CRP (β = 24.4, P = 0.05; 95% CI[0.24-48.63]) and neutrophil counts (β = 0.9, P = 0.03; 95% CI[0.09-1.70]).ConclusionThe low diversity of genotypes may be explained by an evolutionary advantage of the most common lineages over other lineages combined with optimal conditions for transmission, such as overcrowding and inadequate ventilation. The induction of higher levels of acute phase reactants in patients infected by ‘modern’ lineage isolates compared to ‘ancient’ lineages may suggest increased virulence among ‘modern’ lineage isolates.
Highlights
There is increasing evidence to suggest that different Mycobacterium tuberculosis lineages cause variations in the clinical presentation of tuberculosis (TB)
The members of the M. tuberculosis Complex show a high degree of sequence similarity at the genome level [1] the combination of different forms of genotyping such as Single Nucleotide Sequencing (SNP) and Large Sequence Polymorphisms (LSP) have shown that some lineages are associated with increased transmissibility, whereas others induce stronger host inflammatory responses [2]
Certain genotypes/lineages of M. tuberculosis are more likely to cause active TB in human populations from a distinct genetic ancestry [3,4] suggesting an adaptation by the pathogen to its human host
Summary
There is increasing evidence to suggest that different Mycobacterium tuberculosis lineages cause variations in the clinical presentation of tuberculosis (TB). Certain genotypes/lineages of M. tuberculosis are more likely to cause active TB in human populations from a distinct genetic ancestry [3,4] suggesting an adaptation by the pathogen to its human host. A recent study by Hanekom et al [5] showed that this lineage consists of 7 sub-lineages, where one sub-lineage shows increased resistance to anti-TB drugs, whereas another sub-lineage shows an increased level of transmissibility. This finding shows how differences among the infectious agents may impact their ability to cause infection and disease among their hosts
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