Mycobacterium tuberculosis polyclonal infections through treatment and recurrence

Abstract

Background Mixed/polyclonal infections due to different genotypes are reported in Tuberculosis. The current study was designed to understand the fate of mixed infections during the course of treatment and follow-up and its role in disease pathogenesis. Methods Sputum samples were collected on 0,1,2,3,6,12 and 24 months from 157 treatment-naïve patients, cultures subjected to Drug-Susceptibility-testing (MGIT 960), spoligotyping, MIRU-VNTR and SNP genotyping. All isolated colonies on thin layer agar (7H11) were subjected to spoligotyping. Findings One thirty three baseline cultures were positive (133/157, 84.7%), 43(32.3%) had mixture of genotypes. Twenty-four of these patients (55.8%) showed change in genotype while six showed different drug-susceptibility patterns while on treatment. Twenty-three (53.5%) patients with polyclonal infections showed resistance to at least one drug compared to 10/ 90 (11.1%) monoclonal infections (P<0.0001). Eight patients had recurrent TB, two with a new genotype and two with altered phenotypic DST. Conclusions The coexistence of different genotypes and change of genotypes during the same disease episode, while on treatment, confirms constancy of polyclonal infections. The composition of the mixture of genotypes and the relative predominance may be missed by culture due to its limit of detection. Polyclonal infections in TB could be a rule rather than exception and challenges the age-old dogma of reactivation/reinfection.

Effect of mixed Mycobacterium tuberculosis infection on rapid molecular diagnostics among patients starting MDR-TB treatment in Uganda

“…However it disagrees with [29] who reported an association between mixed MTB infection and age and sex. In addition, [30] also reported strong association between having mixed MTB infection and CAS1_Delhi lineage (Lineage 3) which disagrees with this ndings. The difference in these ndings could be attributed to the geographical location where the study was done since the different MTB lineages are geographically located except Lineage 4 which seems to be widely distributed [31].…”

Molecular Epidemiology and Polymorphism Analysis in Drug-Resistant Genes in M. tuberculosis Clinical Isolates from Western and Northern India

“…A recent study points out to the mixed or polyclonal infections in India that may occur due to infection by more than one genotypes during treatment, making drug resistance even a bigger nuisance. 74 While some reports discuss Manu ancestral lineage as an artefact due to co-infection by strains of Lineage 2 and 4, we are not in a position to comment, as this study did not examine any co-infection or polyclonal infections. 75 , 76 …”

Effect of mixed Mycobacterium tuberculosis infection on rapid molecular diagnostics among patients starting MDR-TB treatment in Uganda

“…However it disagrees with Pang et al (2015) [ 29 ] who reported an association between mixed MTB infection and age and sex. In addition, Pandey et al (2020) [ 30 ] also reported strong association between having mixed MTB infection and CAS1_Delhi lineage (Lineage 3) which disagrees with this findings. The difference in these findings could be attributed to the geographical location as Lineage 4 is the dominant lineage in Uganda.…”