Classifying recurrent Mycobacterium tuberculosis cases in Georgia using MIRU-VNTR typing

Maghradze, Nino; Jugheli, Levan; Borrell, Sònia; Tukvadze, Nestani; Aspindzelashvili, Rusudan; Avaliani, Zaza; Reither, Klaus; Gagneux, Sébastien

doi:10.1371/journal.pone.0223610

Cited by 11 publications

(12 citation statements)

References 25 publications

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“…In low-incidence countries, researchers have found the percentage of reinfection ranging from 4% in the United States and Canada to 23% in Italy ( Jasmer et al, 2004 ; Schiroli et al, 2015 ). By contrast, reinfection was the major reason for the recurrent cases, ranging from 17% in Georgia to 69% in South Africa ( Charalambous et al, 2008 ; Maghradze et al, 2019 ). In studies of MTB isolates circulating in China, the rate of reinfection among pulmonary TB patients exhibited great diversity, ranging from 47% in Jiangsu to 61% in Shanghai ( Shen et al, 2006 ; Shao et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Distinguishing Relapse From Reinfection With Whole-Genome Sequencing in Recurrent Pulmonary Tuberculosis: A Retrospective Cohort Study in Beijing, China

Liu

et al. 2021

Front. Microbiol.

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Background: Tuberculosis recurrence is still a major problem for the control of tuberculosis, and the cause of the recurrence is still unclear.Methods: We retrospectively recruited 68 pairs of samples of Mycobacterium tuberculosis (MTB) from recurrent TB cases in Beijing Chest Hospital between January 2008 and December 2019. The whole-genome sequencing was conducted to analyze single-nucleotide polymorphism (SNP) and to identify whether recurrent disease was due to relapse or reinfection. The BACTEC MGIT was performed to compare differences in drug susceptibility profiles between two episodes.Results: 62 (91.2%) out of 68 confirmed recurrence were due to relapse, whereas the remaining six (8.8%) were due to reinfection. And there was a strong association between earlier relapse and underlying chronic diseases. In addition, the MTB isolates from non-diabetic patients had a higher mutation rate than those from diabetic patients. A community transmission was also identified in our cohort. Levofloxacin resistance was the most frequently observed drug resistance for 12.9% relapse cases.Conclusion: The relapse of a previous episode in Beijing. The underlying chronic diseases are associated with an earlier TB relapse. MTB isolates were more prone to develop levofloxacin resistance than moxifloxacin resistance after FQ exposure. The patients at high-risk for relapses deserve more careful investigation.

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Section: Discussionmentioning

confidence: 99%

Distinguishing Relapse From Reinfection With Whole-Genome Sequencing in Recurrent Pulmonary Tuberculosis: A Retrospective Cohort Study in Beijing, China

Liu

et al. 2021

Front. Microbiol.

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“…The standard 24 loci were performed for genotyping of Mycobacterium tuberculosis according to Supply et al (2006) After amplification of extracted DNA, PCR products were examined by 1.5% agarose gel. To analyze the genetic relationship between the first and second episodes, the web application MIRU-VNTRplus was adopted, and the re-infection case was defined as paired isolates with different MIRU-VNTR patterns at two or more than two loci according to phylogenetic lineage identification ( Interrante et al, 2015 ; Maghradze et al, 2019 ).…”

Section: Methodsmentioning

confidence: 99%

Relapse or Re-Infection, the Situation of Recurrent Tuberculosis in Eastern China

Shao

Song

et al. 2021

Front. Cell. Infect. Microbiol.

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PurposeRecurrent tuberculosis (TB) is defined by more than one TB episode per patient and is caused by re-infection with a new Mycobacterium tuberculosis (Mtb) strain or relapse with the previous strain. Recurrence of TB is one important obstacle for End TB strategy in the world and elucidating the triggers of recurrence is important for the current TB control strategy in China. This study aimed to analyze the sources of recurrent TB by the molecular genotyping method.MethodA population-based surveillance was undertaking on all culture-positive TB cases in Jiangsu province, China from 2013 to 2019. Phenotypic drug susceptibility test (DST) by proportion method and mycobacterial interspersed repetitive units-variable number of tandem repeat (MIRU-VNTR) were adopted for drug resistance and genotype detection.ResultsA total of 1451 culture-positive TB patients were collected and 30 (2.06%, 30/1451) TB cases had recurrent TB episodes. Except 7 isolates were failed during subculture, 23 paired isolates were assessed. After genotyping by MIRU-VNTR, 12 (52.17%, 12/23) paired recurrence TB were demonstrated as relapse and 11 (47.83%,11/23) paired cases were identified as re-infection. The average interval time for recurrence was 24.04 (95%CI: 19.37-28.71) months, and there was no significant difference between relapse and re-infection. For the relapsed cases, two paired isolates exhibited drug resistance shifting, while four paired isolates revealed inconsistent drug resistance among the re-infection group including two multidrug-resistant tuberculosis (MDR-TB) at the second episode.ConclusionRelapse and re-infection contributed equally to the current situation of recurrence TB in Jiangsu, China. Besides, more efficient treatment assessment, specific and vigorous interventions are urgently needed for MDR-TB patients, considering obvious performance among re-infection cases.

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“…In order to develop a customized loci set for the Mtb strain population in Georgia, we first re-analyzed a dataset from a previous study of recurrent TB cases, with a retrospective cohort of 32 patients (64 samples) from 2014–2016, typed with the standard 24 loci panel [ 15 ]. Inclusion criteria of the samples for the relapsed cases was availability of the samples in the National Reference Laboratory biobank.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, standard 24-loci MIRU-VNTR typing has been established at the National Reference Laboratory (NRL) of National Center of Tuberculosis and Lung Diseases (NCTLD) in Tbilisi, Georgia, which has been used to differentiate between relapse and reinfection in recurrent TB cases [ 15 ]. In this study, we modified the standard 24-loci MIRU-VNTR panel into a customized stepwise typing approach for the Georgian Mtb population and applied it to a patient population from the penitentiary system.…”

Section: Introductionmentioning

confidence: 99%

Developing customized stepwise MIRU-VNTR typing for tuberculosis surveillance in Georgia

et al. 2022

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Introduction Mycobacterial Interspersed Repetitive Units–Variable Tandem Repeats (MIRU-VNTR) typing has been widely used for molecular epidemiological studies of tuberculosis (TB). However, genotyping tools for Mycobacterium tuberculosis (Mtb) may be limiting in some settings due to high cost and workload. In this study developed a customized stepwise MIRU-VNTR typing that prioritizes high discriminatory loci and validated this method using penitentiary system cohort in the country of Georgia. Methods We used a previously generated MIRU-VNTR dataset from recurrent TB cases (32 cases) in Georgia and a new dataset of TB cases from the penitentiary system (102 cases) recruited from 2014 to 2015. A Hunter-Gaston Discriminatory Index (HGDI) was calculated utilizing a 24 standard loci panel, to select high discriminatory power loci, subsequently defined as the customized Georgia-specific set of loci for initial typing. The remaining loci were scored and hierarchically grouped for second and third step typing of the cohort. We then compared the processing time and costs of the customized stepwise method to the standard 24-loci method. Results For the customized Georgia-specific set that was used for initial typing, 10 loci were selected with a minimum value of 0.32 to the highest HGDI score locus. Customized 10 loci (step 1) typing of 102 Mtb patient isolates revealed 35.7% clustered cases. This proportion was reduced to 19.5% after hierarchical application of 2nd and 3rd step typing with the corresponding groups of loci. Our customized stepwise MIRU-VNTR genotyping approach reduced the quantity of samples to be typed and therefore overall processing time and costs by 42.6% each. Conclusion Our study shows that our customized stepwise MIRU-VNTR typing approach is a valid alternative of standard MIRI-VNTR typing panels for molecular epidemiological investigation in Georgia that saves time, workload and costs. Similar approaches could be developed for other settings.

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Classifying recurrent Mycobacterium tuberculosis cases in Georgia using MIRU-VNTR typing

Cited by 11 publications

References 25 publications

Distinguishing Relapse From Reinfection With Whole-Genome Sequencing in Recurrent Pulmonary Tuberculosis: A Retrospective Cohort Study in Beijing, China

Distinguishing Relapse From Reinfection With Whole-Genome Sequencing in Recurrent Pulmonary Tuberculosis: A Retrospective Cohort Study in Beijing, China

Relapse or Re-Infection, the Situation of Recurrent Tuberculosis in Eastern China

Developing customized stepwise MIRU-VNTR typing for tuberculosis surveillance in Georgia

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