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Recurrent tuberculosis in an urban area in China: Relapse or exogenous reinfection?

ABSTRACT: Recurrent tuberculosis is an important indicator of the effectiveness of tuberculosis control and can occur by relapse or exogenous reinfection. We conducted a retrospective cohort study on all bacteriologically confirmed tuberculosis cases that were successfully treated between 2000 and 2012 in Shanghai, an urban area with a high number but a low prevalence rate of tuberculosis cases and a low prevalence of HIV infection. Genotyping the Mycobacterium tuberculosis from clinical isolates was used to distinguish between relapse and reinfection. In total, 5.3% (710/13,417) of successfully treated cases had a recurrence, a rate of 7.55 (95% CI 7.01-8.13) episodes per 1000 person-years, more than 18 times the rate of tuberculosis in the general population. Patients who were male, age 30-59, retreatment cases, had cavitation, diabetes, drug-resistant or multidrug-resistant tuberculosis in their initial episode of tuberculosis, were at high risk for a recurrence. Among 141 recurrent cases that had paired isolates, 59 (41.8%) had different genotypes, indicating reinfection with a different strain. Patients who completed treatment were still at high risk of another episode of tuberculosis and exogenous reinfection contributed a significant proportion of the recurrent tuberculosis cases. Targeted control strategies are needed to prevent new tuberculosis infections in this setting.

SUBMITTER: Shen X

PROVIDER: S-EPMC5638046 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Recurrent tuberculosis in an urban area in China: Relapse or exogenous reinfection?

Shen Xin X Yang Chongguang C Wu Jie J Lin Senlin S Gao Xu X Wu Zheyuan Z Tian Jiyun J Gan Mingyu M Luo Tao T Wang Lili L Yu Chenlei C Mei Jian J Pan Qichao Q DeRiemer Kathryn K Yuan ZhengAn Z Gao Qian Q

Tuberculosis (Edinburgh, Scotland) 20170131

Recurrent tuberculosis is an important indicator of the effectiveness of tuberculosis control and can occur by relapse or exogenous reinfection. We conducted a retrospective cohort study on all bacteriologically confirmed tuberculosis cases that were successfully treated between 2000 and 2012 in Shanghai, an urban area with a high number but a low prevalence rate of tuberculosis cases and a low prevalence of HIV infection. Genotyping the Mycobacterium tuberculosis from clinical isolates was used ...[more]

PMID: 28237039

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Project description:BackgroundTuberculosis may reoccur due to reinfection or relapse after initially successful treatment. Distinguishing the cause of TB recurrence is crucial to guide TB control and treatment. This study aimed to investigate the source of TB recurrence and risk factors related to relapse in Hunan province, a high TB burden region in southern China.MethodsA population-based retrospective study was conducted on all culture-positive TB cases in Hunan province, China from 2013 to 2020. Phenotypic drug susceptibility testing and whole-genome sequencing were used to detect drug resistance and distinguish between relapse and reinfection. Pearson chi-square test and Fisher exact test were applied to compare differences in categorical variables between relapse and reinfection. The Kaplan-Meier curve was generated in R studio (4.0.4) to describe and compare the time to recurrence between different groups. p < 0.05 was considered statistically significant.ResultsOf 36 recurrent events, 27 (75.0%, 27/36) paired isolates were caused by relapse, and reinfection accounted for 25.0% (9/36) of recurrent cases. No significant difference in characteristics was observed between relapse and reinfection (all p > 0.05). In addition, TB relapse occurs earlier in patients of Tu ethnicity compared to patients of Han ethnicity (p < 0.0001), whereas no significant differences in the time interval to relapse were noted in other groups. Moreover, 83.3% (30/36) of TB recurrence occurred within 3 years. Overall, these recurrent TB isolates were predominantly pan-susceptible strains (71.0%, 49/69), followed by DR-TB (17.4%, 12/69) and MDR-TB (11.6%, 8/69), with mutations mainly in codon 450 of the rpoB gene and codon 315 of the katG gene. 11.1% (3/27) of relapse cases had acquired new resistance during treatment, with fluoroquinolone resistance occurring most frequently (7.4%, 2/27), both with mutations in codon 94 of gyrA.ConclusionEndogenous relapse is the main mechanism leading to TB recurrences in Hunan province. Given that TB recurrences can occur more than 4 years after treatment completion, it is necessary to extend the post-treatment follow-up period to achieve better management of TB patients. Moreover, the relatively high frequency of fluoroquinolone resistance in the second episode of relapse suggests that fluoroquinolones should be used with caution when treating TB cases with relapse, preferably guided by DST results.

Project description:Our study sought to compare the strain types of Clostridium difficile causing initial and recurrent episodes of C. difficile infection (CDI) in adult patients with a first episode of CDI or 1 prior episode of CDI within the previous 90 days. Strains originated from patients who had been entered into two phase 3 randomized clinical trials of fidaxomicin versus vancomycin. Isolates of C. difficile from the initial and recurrent episodes within 28 (± 2) days of cure of CDI were compared using restriction endonuclease analysis (REA) typing. Paired isolates were available from 90 of 194 (46%) patients with recurrent CDI. Patients with isolates available were significantly younger (P = .008) and more likely to be from Canadian sites (P = .0001), compared with patients without isolates. In 75 of 90 subjects (83.3%), the identical REA type strain was identified at recurrence and the initial episode (putative relapse). Early recurrences (0-14 days after treatment completion) were relapses in 86.7% and a new strain (reinfection) in 13.3%. Later recurrences (15-31 days after treatment) were relapses in 76.7% and reinfections in 23.3%. Mean time (± standard deviation) to recurrence was 12.2 (± 6.4) days for relapses and 14.7 (± 6.8) days for reinfections (P = .177). The most common BI/NAP1/027 group and the previous US epidemic REA group J/NAP2/001 had a significantly higher combined rate of recurrence with the same strain (relapse), compared with the other REA groups (39 of 42 [93%] vs 36 of 48 [75%], respectively; P = .023). We found a higher than historic rate of recurrent CDI caused by the same isolate as the original episode, a finding that may be related to the relatively short observation period in this study and the high frequency of isolation of epidemic strains, such as groups BI and J, for which relapse rates may be higher than for other REA groups. Caution in generalizing these observations is required, because the patients studied were younger and more likely to be from Canadian sites than were patients with recurrence who did not provide isolates.

Project description:BackgroundRIFAQUIN was a tuberculosis chemotherapy trial in southern Africa including regimens with high-dose rifapentine with moxifloxacin. Here, the application of whole-genome sequencing (WGS) is evaluated within RIFAQUIN for identifying new infections in treated patients as either relapses or reinfections. WGS is further compared with mycobacterial interspersed repetitive units-variable number tandem repeats (MIRU-VNTR) typing. This is the first report of WGS being used to evaluate new infections in a completed clinical trial for which all treatment and epidemiological data are available for analysis.MethodsDNA from 36 paired samples of Mycobacterium tuberculosis cultured from patients before and after treatment was typed using 24-loci MIRU-VNTR, in silico spoligotyping and WGS. Following WGS, the sequences were mapped against the reference strain H37Rv, the single-nucleotide polymorphism (SNP) differences between pairs were identified, and a phylogenetic reconstruction was performed.ResultsWGS indicated that 32 of the paired samples had a very low number of SNP differences (0-5; likely relapses). One pair had an intermediate number of SNP differences, and was likely the result of a mixed infection with a pre-treatment minor genotype that was highly related to the post-treatment genotype; this was reclassified as a relapse, in contrast to the MIRU-VNTR result. The remaining three pairs had very high SNP differences (>750; likely reinfections).ConclusionsWGS and MIRU-VNTR both similarly differentiated relapses and reinfections, but WGS provided significant extra information. The low proportion of reinfections seen suggests that in standard chemotherapy trials with up to 24 months of follow-up, typing the strains brings little benefit to an analysis of the trial outcome in terms of differentiating relapse and reinfection. However, there is a benefit to using WGS as compared to MIRU-VNTR in terms of the additional genotype information obtained, in particular for defining the presence of mixed infections and the potential to identify known and novel drug-resistance markers.

Project description:ImportanceDespite posing a significant challenge to global tuberculosis (TB) elimination efforts, recurrent TB remains understudied due to the challenges of long-term observation.ObjectiveTo investigate the burden of recurrent TB using data from patients with pulmonary TB (PTB) in China.Design, setting, and participantsThis retrospective cohort study included all bacteriologically confirmed or clinically diagnosed PTB cases reported to the Tuberculosis Information Management System with completed or successful treatment outcomes from January 1, 2005, to December 31, 2021. Data were analyzed from July 15, 2022, to October 28, 2023.ExposuresNewly diagnosed PTB was classified into primary, hematogenous disseminated, or secondary PTB.Main outcomes and measuresThe primary outcome was the annual recurrence rate, stratified by disease classification, over the 17-year observation period. The recurrence rate for year n was calculated by dividing the number of patients with recurrent TB in year n by observed person-years in year n. The secondary outcome was the annual proportion of recurrent TB among reported cases and associated risk factors.ResultsOf 13 833 249 patients with TB reported to the Tuberculosis Information Management System, 10 482 271 with PTB met the inclusion criteria. Of these, 68.9% were male, 22.3% were 65 years or older, 89.6% were of Han ethnicity, and 68.4% were agricultural workers. A total of 413 936 patients experienced a recurrent TB episode after successful treatment, resulting in an overall recurrence rate of 0.47 (95% CI, 0.47-0.48) per 100 person-years. The recurrence rate for patients with primary PTB was 0.24 (95% CI, 0.22-0.26) per 100 person-years; for hematogenous disseminated PTB, 0.37 (95% CI, 0.36-0.38) per 100 person-years; and for secondary PTB, 0.48 (95% CI, 0.47-0.48) per 100 person-years. The cumulative proportion of recurrences within the first 2 years accounted for 48.9% of all recurrent cases. The proportion of recurrent cases among notified incident cases increased 1.9-fold from 4.7% in 2015 to 8.8% in 2021. Among other factors, ages 45 to 64 years (adjusted hazard ratio, 1.77 [95% CI, 1.65-1.89]) and having completed treatment (adjusted hazard ratio, 1.16 [95% CI, 1.14-1.18]) were identified as associated with recurrence.Conclusions and relevanceIn this retrospective cohort study, the PTB recurrence rate was substantially higher than the incidence, and the proportion of recurrent cases increased. Almost half of the recurrence occurred within the first 2 years, suggesting that routine posttreatment follow-up may represent an important strategy for accelerating TB elimination.

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Recurrent tuberculosis in an urban area in China: Relapse or exogenous reinfection?

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Recurrent tuberculosis in an urban area in China: Relapse or exogenous reinfection?

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