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

Abstract

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.

Endogenous relapse and exogenous reinfection in recurrent pulmonary tuberculosis: A retrospective study revealed by whole genome sequencing

“…In the present study, we found that the acquisition of resistance to fluoroquinolones was the most common during treatment, and this observation was further rationalized by genotypic resistance prediction based on wholegenome sequencing. Similar results have been reported elsewhere (Zong et al, 2018;Du et al, 2021). Although the exact cause of this phenomenon remains unclear, it can be partially explained by the abuse and misuse of fluoroquinolones.…”

“…Studies of countries with low to moderate TB incidence found that the percentage of reinfection ranging from 10% in Switzerland to 33% in Spain (Schiroli et al, 2015), while reinfection was common in studies of high-burden countries, ranging from 23% in India to 68-77% in South Africa (Sahadevan et al, 1995;van Rie et al, 1999;Charalambous et al, 2008). Our study found that 25% of TB recurrence were attributed to reinfection, which was comparable to the proportion reported in Jiangsu (28.9%) (Liu et al, 2022), but much higher than that reported in Beijing (8.8%) (Du et al, 2021). Several reasons could be responsible for such variation of the percentage of reinfection.…”

“…Understanding the proportion of reinfection and relapse will help to implement better post-treatment follow-up and reduce TB burden. Unexpectedly high rates of reinfection suggest that reducing the risk of TB transmission is fundamental, while higher rates of relapse suggest that TB control should focus on improving the efficacy of the first-episode treatment regimen (Folkvardsen et al, 2020;Du et al, 2021). Numerous studies have shown that the proportion of TB recurrence due to exogenous reinfection varies by regions (Bandera et al, 2001;Verver et al, 2005;Zong et al, 2018;Liu et al, 2022).…”

“…The proper discrimination between relapse and reinfection is essential for adjusting TB control measures. High relapse rates indicate inadequate TB treatment, whereas high rates of reinfection reveal poor TB cases management with many missed TB cases circulating in the community (Folkvardsen et al, 2020;Du et al, 2021).…”

Determination of critical concentration for drug susceptibility testing of Mycobacterium tuberculosis against para-aminosalicylic acid with clinical isolates with thyA, folC and dfrA mutations

“…The high-quality DNA samples underwent whole genome sequencing (WGS) using Illumina HiSeq 2000 platform. The raw sequence data were aligned to the MTB H37Rv reference genome (NC000962.3), and the single nucleotide polymorphism (SNP) and insertion-deletion (InDel) of the target genome were identified as previously described [ 16 ]. The TB-Profiler online informatics platform ( https://github.com/jodyphelan/TBProfiler ) was used to identified drug resistance specific mutations.…”