Cumulative risk of recurrence of TB by follow-up time (and its pointwise 95% confidence limits). a Overall cohort; (b) By gender; (c) By anatomical site of disease; (d) Only culture positive TB 

Cumulative risk of recurrence of TB by follow-up time (and its pointwise 95% confidence limits). a Overall cohort; (b) By gender; (c) By anatomical site of disease; (d) Only culture positive TB 

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Background We investigated the epidemiology and prevalence of potential risk factors of tuberculosis (TB) recurrence in a population-based registry cohort of 8084 TB cases between 1995 and 2013. Methods An episode of recurrent TB was defined as a case re-registered in the National Infectious Disease Register at least 360 days from the date of the i...

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... median follow-up time of cases in the cohort of 8084 TB cases was 6.1 years (IQR 2.7-11.1 years). The recurrence occurred within less than 2 years in 25 (50%), two to less than 4 years in 8 (16%), and later in 17 cases (34%) (Fig. 2a). No recurrences occurred in females and for extrapulmonary cases after the first 2 years (Fig. 2b and c). In univariate analysis of variables available for the national cohort, the cumulative risks of recurrence between males and females, and between pulmonary and extrapulmonary TB did not differ statistically significantly at 1 and 2 ...
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... median follow-up time of cases in the cohort of 8084 TB cases was 6.1 years (IQR 2.7-11.1 years). The recurrence occurred within less than 2 years in 25 (50%), two to less than 4 years in 8 (16%), and later in 17 cases (34%) (Fig. 2a). No recurrences occurred in females and for extrapulmonary cases after the first 2 years (Fig. 2b and c). In univariate analysis of variables available for the national cohort, the cumulative risks of recurrence between males and females, and between pulmonary and extrapulmonary TB did not differ statistically significantly at 1 and 2 years of follow-up (Table 3). However, at 18 years of follow-up, the cumulative risk for males was nearly ...
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... of variables available for the national cohort, the cumulative risks of recurrence between males and females, and between pulmonary and extrapulmonary TB did not differ statistically significantly at 1 and 2 years of follow-up (Table 3). However, at 18 years of follow-up, the cumulative risk for males was nearly fourfold compared to females (Fig. 2b), and more than fivefold for pulmonary TB com- pared to extrapulmonary TB (Fig. 2c). The risk of recur- rence decreased with every additional 10 years of age (Table 3). When only cases that were culture positive in all episodes were included, the recurrence rate was simi- lar to that seen in the whole recurrent cases cohort (Fig. 2d). ...
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... between males and females, and between pulmonary and extrapulmonary TB did not differ statistically significantly at 1 and 2 years of follow-up (Table 3). However, at 18 years of follow-up, the cumulative risk for males was nearly fourfold compared to females (Fig. 2b), and more than fivefold for pulmonary TB com- pared to extrapulmonary TB (Fig. 2c). The risk of recur- rence decreased with every additional 10 years of age (Table 3). When only cases that were culture positive in all episodes were included, the recurrence rate was simi- lar to that seen in the whole recurrent cases cohort (Fig. 2d). Whether the first episode occurred prior to versus after 2007 did not have a ...
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... to females (Fig. 2b), and more than fivefold for pulmonary TB com- pared to extrapulmonary TB (Fig. 2c). The risk of recur- rence decreased with every additional 10 years of age (Table 3). When only cases that were culture positive in all episodes were included, the recurrence rate was simi- lar to that seen in the whole recurrent cases cohort (Fig. 2d). Whether the first episode occurred prior to versus after 2007 did not have a significant association with the risk of recurrence (Table ...

Citations

... A WHO report estimated that 6.8% of TB cases recurred worldwide in 2019 [11], and recurrence occurs not only in high TB incidence countries, but also in low countries [12][13][14]. A retrospective study of surveillance data and clinical records in Finland showed 0.6% of TB cases were recurrent from 1995 to 2013 [15], and 1.3% of TB cases were recurrent in Barcelona from 2003 to 2006 [12], and the proportion of recurrent cases between 4.2 and 5.7% in the United States during 1993-2010 [16]. In addition, 5.3% of successfully treated bacteriologically confirmed cases had a recurrence in Shanghai [5], China, and 6.8% in Beijing [6]. ...
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Background Recurrence continues to place significant burden on patients and tuberculosis programmes worldwide, and previous studies have rarely provided analysis in negative recurrence cases. We characterized the epidemiological features of recurrent pulmonary tuberculosis (PTB) patients, estimated its probability associated with different bacteriology results and risk factors. Methods Using 2005–2018 provincial surveillance data from Henan, China, where the permanent population approximately were 100 million, we described the epidemiological and bacteriological features of recurrent PTB. The Kaplan–Meier method and Cox proportional hazard models, respectively, were used to estimate probability of recurrent PTB and risk factors. Results A total of 7143 (1.5%) PTB patients had recurrence, and of 21.1% were bacteriological positive on both laboratory tests (positive–positive), and of 34.9% were negative–negative. Compared with bacteriological negative recurrent PTB at first episodes, the bacteriological positive cases were more male (81.70% vs 72.79%; P < 0.001), higher mortality risk (1.78% vs 0.92%; P = 0.003), lower proportion of cured or completed treatment (82.81% vs 84.97%; P = 0.022), and longer time from onset to end-of-treatment. The probability of recurrence was higher in bacteriological positive cases than those in bacteriological negative cases (0.5% vs 0.4% at 20 months; P < 0.05). Conclusions Based on patient’s epidemiological characteristics and bacteriological type, it was necessary to actively enact measures to control their recurrent.
... Likewise, higher reinfection rates of 1.5-2.8% have been found in countries with a high incidence of TB compared with 0.1-0.3% in countries with a low incidence of TB [4,[8][9][10][11][12][13][14][15][16][17][18][19][20]. ...
... Even though risk factors for reactivation of TB in countries with a low TB incidence have been described, previous studies have had limited power to explore the findings over an extended time period. Additionally, only a few studies explored the effect of interrupted treatment on the risk of reactivation [6,13]. ...
... [6][7][8][9] and reinfection rates of 0.1-0.3% [4,[8][9][10][11][12][13][14][15][16][17][18][19][20]. ...
Article
Background Not all treated tuberculosis (TB) patients achieve long-term recovery and reactivation rates reflect effectiveness of TB treatment. Aim We aimed to estimate rates and risk factors of TB reactivation and reinfection in patients treated in the Netherlands, after completed or interrupted treatment. Methods Retrospective cohort study of TB patients with available DNA fingerprint data, registered in the Netherlands Tuberculosis register (NTR) between 1993 and 2016. Reactivation was defined as an identical, and reinfection as a non-identical Mycobacterium tuberculosis strain in sequential episodes. Results Reactivation rate was 55/100,000 person-years (py) for patients who completed, and 318/100,000 py for patients who interrupted treatment. The risk of reactivation was highest in the first 5 years after treatment in both groups. The incidence rate of reactivation was 228/100,000 py in the first 2 years and 57/100,000 py 2–5 years after completed treatment. The overall rate of reinfection was 16/100,000 py. Among those who completed treatment, patients with male sex, mono or poly rifampicin-resistant TB and a previous TB episode had significantly higher risk of reactivation. Extrapulmonary TB was associated with a lower risk. Among patients who interrupted treatment, directly observed treatment (DOT) and being an undocumented migrant or people experiencing homelessness were associated with a higher risk of reactivation. Conclusions Both patients who completed or interrupted TB treatment should be considered as risk groups for reactivation for at least 2–5 years after treatment. They patients should be monitored and guidelines should be in place to enhance early detection of recurrent TB.
... Although similar trends were also reported from other studies, the risk of recurrence among successfully treated patients compared with rates of initial episode in general population in our study was much greater than that observed in other studies. [18][19][20][21] Previous studies reported that 58.2-69.0% of recurrent TB in China were resulted from relapse of the original M. tuberculosis strain rather than from reinfection with a new strain. 22-23 However, we are not able to comment on this as we did not test those who represented with TB to establish if it was relapse or reinfection. ...
... Similar trends were also observed in other studies. 18,19,21 These findings suggest that TB patients should be monitored even after completion of their treatments, particularly during the first 3 years. Although the study sites were not high TB incidence settings, with these rates of recurrence, special attention should be given in the first year following completion of initial treatment as relapse generally happens earlier than reinfection. ...
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Objectives To determine tuberculosis (TB) recurrence in previously successfully treated patients in routine program setting and baseline characteristics associated with TB recurrence. Methods A prospective longitudinal study in Jiangxi Province, China. Patients, ≥14 years old, were consecutively registered and were followed-up for 7-year to assess TB recurrence against patients’ individual baseline data that was entered into a database at TB registration. Results There were 800 TB patients registered at baseline and 634 (79.2%) of them completed anti-TB treatments. Fifty nine (9.3%) died and 21 (3.3%) were lost to follow-up over the follow-up period. There were 96 patients with recurrent episodes (total incidence 15.2% or annual incidence 2,200/100,000). Of the recurrent cases, 53 (55.2%) happened within 2-year after completion of anti-TB treatments. After controlling confounding factors, risk of TB recurrence was significantly higher in age range 34-73 years (P<0.01) and current smokers (P<0.01). Conclusions Overall recurrence rate among previously treated TB patients was much higher compared to initial incidence in the same population (61-98/100,000) and settings with similar TB incidence. TB programs should consider closer monitoring for these patients for early detection of recurrence. Particular attention should be given to those between 34-73 years and those who use tobacco products.
... The unavailability of whole genome sequencing (WGS) to more definitively exclude re-infection for our cases with same DNA fingerprints for both disease episodes was another study limitation. Although MIRU-VNTR and spoligotyping A c c e p t e d M a n u s c r i p t have been used successfully in Northern European countries to distinguish re-infection and relapse (23,24), it has been shown that these methods lack discriminatory power for strains of non-Euro-American lineage (25,26). The Beijing family strain and the East-African-Indian (EAI) strain account for 47% and 24% respectively of the strains in the country (27). ...
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Background Previously treated ie. recurrent tuberculosis (TB) cases account for ~7-8% of incident TB globally and in Singapore. Molecular fingerprinting has enabled the differentiation of these patients into relapsed or re-infection cases. Methods Patient demographics, disease characteristics and treatment information were obtained from the national TB notification registry and TB Control Unit. We performed a retrospective, case-control study to evaluate factors associated with recurrent TB disease in Singapore citizens and Permanent Residents with culture-positive TB from 2006 to 2013 and who developed a second episode of culture-positive TB up to 2016 using multivariable logistic regression analyses. Results 91 cases with culture-positive first and recurrent TB disease episodes were identified. Recurrent TB was associated with age ≥60 years (adjusted odds ratio [aOR] 1.98, 95% confidence interval [CI] 1.09-3.61), male gender (aOR 2.29, 95% CI 1.22–4.51), having concomitant pulmonary and extrapulmonary TB (aOR 3.10, 95% CI 1.59–6.10) and extrapulmonary TB alone (aOR 3.82, 95% CI 1.12-13.31); and was less likely in non-Malays (aOR 0.52, 95% CI 0.27–0.99). DNA fingerprinting results for both episodes in 49 cases differentiated these into 28 relapsed and 21 re-infection cases. Relapse was associated with having concomitant pulmonary and extrapulmonary TB (aOR 9.24, 95% CI 2.50–42.42), and positive sputum acid fast bacilli smear (aOR 3.95, 95% CI 1.36–13.10). Conclusion Relapse and re-infection contributed to 57% and 43% respectively of recurrent TB in Singapore. Our study highlights the under-appreciated association of concomitant pulmonary and extrapulmonary TB as a significant risk factor for disease relapse.
... 19 In this study, recurrent pulmonary TB is significantly higher in male patients, confirming that males become one of the risk factors contributing to recurrent cases. 20,21 Other risk factors associated with recurrent TB cases include smoking, poor treatment adherence, uncontrolled HIV-comorbid infection, and specific clinical pictures such as residual cavitation, more significant area of involved lung tissue, and positive sputum culture at two months of first treatment. 3 Previous studies have shown associations between TB recurrence and drug resistance. ...
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Purpose: N-acetyltransferase-2 enzyme in the liver, encoded by NAT2 gene, plays a central role in metabolizing tuberculosis (TB) drug isoniazid (INH). Low compliance of patients toward six-month TB therapy and internal host factors, ie comorbid diseases, immune status, and genetic profiles, are factors leading to treatment failure and recurrence of pulmonary TB infection. This study aimed to explore the NAT2 acetylator status among newly diagnosed and recurrent pulmonary TB patients in eastern part of Indonesia. Patients and methods: Archived DNA of TB patients (n=124) and healthy controls (n=124) were sequenced, and NAT2 acetylator status was determined, then categorized as fast, intermediate, or slow acetylators. Pulmonary TB patients who had no previous TB treatment history were designated as newly diagnosed pulmonary TB, whereas patients with a history of TB treatment were designated as recurrent pulmonary TB. The demographic, clinical, and microbiological data between pulmonary TB groups were compared, and acetylator status was described among groups. Results: Male was more significantly prevalent in the recurrent pulmonary TB group (p=0.025), and anemia was more prevalent in new pulmonary TB (p=0.003). The acetylator status in pulmonary TB patients compared to healthy controls were rapid (33.9% vs 48.1%), intermediate (57.8% vs 33.0%), and slow acetylators (8.3% vs 18.9%), respectively. Interestingly, the rapid and intermediate acetylator were significantly more prevalent in pulmonary TB patients than in healthy controls (p=0.023, OR=2.58 (1.12-5.97). Furthermore, no differences were found in acetylator status between new and recurrent pulmonary (p=0.776). Conclusion: Rapid and intermediate acetylators status predominated the pulmonary TB patients in Kupang, eastern part of Indonesia, postulating different genetic makeup in this area. As the pulmonary TB patients in Kupang exhibit more rapid acetylator phenotype, the acetylator status might be relevant to be checked before TB therapy for adjusting treatment dose to prevent drug resistances.
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There is a growing awareness of the importance of sex and gender in medicine and research. Women typically have stronger immune responses to self and foreign antigens than men, resulting in sex-based differences in autoimmunity and infectious diseases. In both animals and humans, males are generally more susceptible than females to bacterial infections. At the same time, gender differences in health-seeking behavior, quality of health care, and adherence to treatment recommendations have been reported. This review explores our current understanding of differences between males and females in bacterial diseases. We describe how genetic, immunological, hormonal, and anatomical factors interact to influence sex-based differences in pathophysiology, epidemiology, clinical presentation, disease severity, and prognosis, and how gender roles affect the behavior of patients and providers in the health care system.