The impact of mixed infections on the interpretation of molecular epidemiology studies of tuberculosis

Shin, Sanghyuk S.; Modongo, Chawangwa; Zetola, Nicola M.

doi:10.5588/ijtld.15.1024

Cited by 9 publications

(6 citation statements)

References 5 publications

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“…Our findings confirmed previous observations that minority M. tuberculosis variants with drug resistance conferring mutations can be detected by WGS, even when this is not apparent on pDST (4). Even if not MDR, unrecognised minority variants with drug resistance could be selected during sub-optimal treatment, leading to treatment failure and clinical relapse (27).…”

Section: Discussionmentioning

confidence: 99%

Genomic markers of drug resistance inMycobacterium tuberculosispopulations with minority variants

Zhang

Lam

Martínez

et al. 2023

Preprint

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Minority variants ofMycobacterium tuberculosisharbouring mutations conferring resistance can become dominant populations during tuberculosis (TB) treatment, leading to treatment failure. Our understanding of drug resistant within-host sub-populations and the frequency of resistance conferring mutations in minority variants remains limited.M. tuberculosissequences recovered from liquid cultures of culture-confirmed TB cases notified between January 2017 and December 2021 in New South Wales, Australia were examined. Potential drug resistance conferring minority variants were identified using LoFreq, and mixed populations of differentM. tuberculosisstrains (³100 SNPs apart) were examined using QuantTB. A total of 1831 routinely sequencedM. tuberculosisstrains were included in the analysis. Drug resistance conferring minority variants were detected in 3.5% (65/1831) of sequenced cultures; 84.6% (55/65) had majority strains that were drug susceptible and 15.4% (10/65) had majority strains that were drug resistant. Minority variants with high confidence drug resistance conferring mutations were 1.5 times more common when the majority strains were drug resistant. MixedM. tuberculosisstrain populations were documented in 10.0% (183/1831) of specimens. Minority variants with high confidence drug resistance conferring mutations were more frequently detected in mixedM. tuberculosisstrain populations (2.7%, 5/183) than in single strain populations (0.6%, 10/1648; p=0.01). Drug resistant minority variants require careful monitoring in settings that implement routineM. tuberculosissequencing. The frequency with which drug resistant minority variants are detected is influenced by selective culture methods and culture-independent sequencing should provide a more accurate picture.

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Section: Discussionmentioning

confidence: 99%

Genomic markers of drug resistance inMycobacterium tuberculosispopulations with minority variants

Zhang

Lam

Martínez

et al. 2023

Preprint

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“…WGS directly from clinical samples is a great current scientific challenge due to the presence of large amounts of accompanying DNA from the flora of the respiratory tract and human cells that interfere with this sequencing tool. Different approaches have been tested to try to overcome these interferences, such as selectively eliminating the human DNA present in the clinical sample ( 14 ) or using MTB DNA enrichment systems, e.g., specific biotinylated RNA baits ( 4 , 8 , 15 , 21 , 22 ).…”

Section: Discussionmentioning

confidence: 99%

“…Both clonal heterogeneity events may involve strains with the same or different drug susceptibility; the latter is known as heteroresistance and is an increasing public health concern. Patients with undiagnosed heteroresistance receive suboptimal treatments; consequently, resistant bacterial populations may be selected due to antibiotic pressure, leading to poor patient outcomes ( 4 ). Detection of mixed infections is key even in the absence of heteroresistance, as they may be associated with a worse course of the disease, although the underlying reasons for this phenomenon are still unknown ( 5 – 7 ).…”

Section: Introductionmentioning

confidence: 99%

Detection of Minority Variants and Mixed Infections in Mycobacterium tuberculosis by Direct Whole-Genome Sequencing on Noncultured Specimens Using a Specific-DNA Capture Strategy

Lozano

Lanza

Suárez‐González

et al. 2021

mSphere

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We present a new strategy to identify mixed infections and minority variants in Mycobacterium tuberculosis by whole-genome sequencing. The objective of the strategy is the direct detection in patient sputum; in this way, minority populations of resistant strains can be identified at the time of diagnosis, facilitating identification of the most appropriate treatment for the patient from the first moment.

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“…MDR TB treatment success rates increased from 67% to 86% as CD4 counts increased from < 100 to > 350 cells/mm 3 at the time of diagnosis. The importance of early diagnosis and treatment of HIV is once again highlighted [10].…”

Section: Tb In Resource Limited Countriesmentioning

confidence: 99%

Tuberculosis: A Report from CROI 2016

Kasten

2016

Journal of Clinical Tuberculosis and Other Mycobacterial Diseas

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The Conference on Retroviruses and Opportunistic Infections (CROI) is a major annual scientific meeting on HIV/AIDS and associated conditions. Tuberculosis (TB) is the number one cause of death among people living with HIV in developing countries and is the subject of numerous CROI presentations. This report will focus on the presentations at CROI that the author believes are most relevant to clinicians, the public health community and investigators interested in tuberculosis.

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The impact of mixed infections on the interpretation of molecular epidemiology studies of tuberculosis

Cited by 9 publications

References 5 publications

Genomic markers of drug resistance inMycobacterium tuberculosispopulations with minority variants

Genomic markers of drug resistance inMycobacterium tuberculosispopulations with minority variants

Detection of Minority Variants and Mixed Infections in Mycobacterium tuberculosis by Direct Whole-Genome Sequencing on Noncultured Specimens Using a Specific-DNA Capture Strategy

Tuberculosis: A Report from CROI 2016

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