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Understanding factors associated with increased risk for tuberculosis (TB) recurrence is essential in lowering the TB burden. We aimed to quantify the burden, risk factors, and timing of TB presumptive recurrence.We analyzed test results from 2013 to 2017 in the South African National Health Laboratory Service's database. We defined a person's TB episode to start with their first positive TB test. In the absence of treatment outcome data, we assumed the episode concluded 6 months later for rifampicin-susceptible TB (RS-TB) and 18 months later for rifampicin-resistant TB (RR-TB), provided that at least one negative smear or culture test was recorded within this period. We defined a presumptive recurrent TB episode to start with a positive TB test after the completion of a prior episode. We calculated recurrence measures stratified by various demographics and RR-TB status.Of 574,316 people with RS-TB, 4.7% experienced at least one presumptive recurrent TB episode. Higher local TB notification rates, HIV coinfection, and males experienced higher recurrence rates. Most (89.4%) of the first RS-TB recurrences occurred within a year of the initial episode.Our findings of when and among whom recurrent TB is more likely to occur can be used to assist early interventions and inform impact on patient care..

Background: Mono-resistance to rifampicin/isoniazid increases poor treatment outcomes and the risk of multi-drug resistance (MDR) in tuberculosis (TB) patients. Limited information exists about mono-resistance status of TB patients in Uttar Pradesh, North India. This study aimed to estimate the burden of rifampicin and isoniazid mono-resistance in Western Uttar Pradesh., Methods and Results: 153 sputum samples of suspected pulmonary tuberculosis patients were processed to isolate Mycobacterium tuberculosis using the Lowenstein-Jensen (L-J) culture medium. The isolates were identified using an immuno-chromatographic test and IS6110 PCR. The confirmed Mycobacterium tuberculosis isolates were tested for drug susceptibility testing against rifampicin and isoniazid anti-tuberculosis drugs. The results of the drug susceptibility testing were compared with demographic information and analyzed statistically. Out of 153 sputum samples, 83 (54.24%) samples were positive for growth on L-J medium, including 82 (98.79%) Mycobacterium tuberculosis isolates. Of the 82 Mycobacterium tuberculosis isolates, 16 (19.51%), 7 (8.54%), and 5 (6.10%) isolates were MDR, mono-resistant to rifampicin and isoniazid, respectively. The occurrence of RIF/INH mono-resistant-TB was higher in patients of male gender, age above 45 years, living in rural conditions, history of weight loss, and previous anti-TB treatment, but the effect was not statistically significant., Conclusions: The study reported the status of rifampicin and isoniazid mono-resistance among TB patients and highlighted the need for continuous monitoring and improved intervention for the initial detection of mono-drug-resistant cases. This will improve clinical treatment outcomes and decrease the rate of drug-resistant TB in Uttar Pradesh, North India., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The spread of multidrug-resistant tuberculosis (MDR-TB) poses a significant challenge to TB control efforts. This study evaluated the treatment outcomes and associated factors among patients receiving treatment for MDR-TB in southern Ethiopia., Methods: A retrospective follow-up study covering ten years, from 2014 to 2023, analyzed the records of confirmed cases of pulmonary TB admitted to Yirgalem General Hospital, an MDR-TB treatment initiation center in the Sidama Region. To compare the successful treatment outcomes across the years, a chi-square test of independence was conducted. Bivariate and multivariable logistic regression models were used to identify factors associated with treatment outcomes for MDR-TB., Results: Out of 276 confirmed MDR-TB cases, 4(1.4%) were diagnosed with resistance to second-line drugs (SLDs). Overall, 138 patients achieved favourable treatment outcomes, resulting in a treatment success rate of 50.0% [95% CI 44.1-55.9%]. Among these 138 patients, 105(76.1%, 95 CI 68.7-83.5%) were cured, while 33(23.9%, 95 CI 16.5-31.3%) completed their treatment. The successful treatment outcomes varied significantly across the years, ranging from 3.6% in 2020 to 90% in 2021. The analysis indicated a statistically significant difference in treatment outcomes when considering data from 2014 to 2023 (χ 2  = 44.539, p = 0.001). The proportion of patients with deaths, lost-to-follow-up (LTFU), treatment failures and not evaluated were 7.9% [95% CI 4.8-11.2%], 10.9% [95% CI 7.2-14.6%), 2.2% [95% CI 1.1-3.3%), and 28.9% [95% CI 23.7-34.2%] respectively. Individuals with a positive HIV status had significantly lower odds of a favorable treatment outcome [AOR = 0.628, 95% CI (0.479-0.824), p = 0.018]. Similarly, patients with a BMI of less than 18 are more likely to have unfavorable treatment outcomes compared to those with a BMI of 18 or higher [AOR = 2.353, 95% CI 1.404-3.942, p < 0.001]., Conclusion: The study revealed a concerning 1.4% prevalence of additional resistance to SLDs. The 50% rate of unfavorable treatment among MDR-TB cases exceeds the target set by the WHO. A significant number of patients (10.9%) were LTFU, and the 28.9% categorized as 'not evaluated' is also concerning. Enhanced strategic interventions are needed to reduce such cases, and factors associated with poor treatment outcomes should receive greater attention. Future prospective studies can further explore the factors influencing improved treatment success., (© 2024. The Author(s).)

Background: India, with the highest global burden of tuberculosis (TB) and drug-resistant TB, aims to eliminate TB by 2025. Yet, limited evidence exists on drug resistance patterns and retreatment among patients with silico-tuberculosis. This study explores these patterns and assesses the impact of silicosis on TB retreatment in India., Methods: This secondary data analysis stems from a larger retrospective cohort study conducted in Khambhat, Gujarat, between January 2006 and February 2022. It included 138 patients with silico-tuberculosis and 2,610 TB patients without silicosis. Data from the Nikshay TB information portal were linked with silicosis diagnosis reports from the Pneumoconiosis Board using the unique Nikshay ID as the linking variable. Drug-resistant TB was defined as resistance to any anti-TB drug recorded in Nikshay. Retreatment refers to TB patients who have previously undergone anti-TB treatment for one month or more and need further treatment. Recurrent TB denotes patients who were previously declared cured or had completed treatment but later tested positive for microbiologically confirmed TB. Multivariable logistic regression was used to determine the impact of co-prevalent silicosis on drug resistance and retreatment., Results: Patients with silico-tuberculosis showed a higher proportion of retreatment compared to those without silicosis (55% vs. 23%, p < 0.001). Notably, 28% of patients with silico-tuberculosis were recurrent TB cases, compared to 11% among those without silicosis. Regarding drug resistance, the silico-tuberculosis group exhibited a higher rate (6% vs. 3%), largely due to rifampicin resistance (5% vs. 2%, p = 0.022). Co-prevalent silicosis was associated with a 2.5 times greater risk of drug-resistant TB (adjusted OR 2.5, 95% CI, 1.1-5.3; p = 0.021). Additionally, patients with silico-tuberculosis had a fourfold increased risk of retreatment for TB (adjusted OR 4, 95% CI, 3-6; p < 0.001)., Conclusions: Co-prevalent silicosis significantly elevates the risk of drug resistance, recurrence, and retreatment among TB patients in India. This study indicates a need for improved treatment protocols and suggests that future research should focus on randomized controlled trials to evaluate appropriate anti-TB regimen and duration of therapy for this high-risk group. Given India's goal to eliminate TB by 2025, addressing the challenges posed by silico-tuberculosis is critical., (© 2024. The Author(s).)

Background: To assess the prevalence and epidemic pattern of multidrug-resistant tuberculosis in Hangzhou City, Zhejiang Province, China during 2012-2022., Methods: All the tuberculosis cases undergoing drug susceptibility testing during 2012-2022 were included in this study. De-identified information was extracted from the electronic database Tuberculosis Information Management System for analysis of drug resistance prevalence in Hangzhou and ecdemic multidrug-resistant tuberculosis which originated from other regions. Chi-square tests were used to compare drug resistance rates between different groups, while Chi-square tests for trend were used to evaluate the change of drug resistance rates over the years of 2012-2022. The sources and destinations of ecdemic multidrug-resistant tuberculosis were illustrated using a Sankey diagram., Results: Of 21,127 cases included in this study, 1119 (5.3%) were multidrug-resistant tuberculosis. A significant decline in multidrug-resistant tuberculosis rates was observed during 2012-2022. There was a significant difference in multidrug-resistant tuberculosis rates among immigrant population and local residents in Hangzhou City. Of 1119 multidrug-resistant tuberculosis cases, 515(46%) were ecdemic multidrug-resistant tuberculosis cases, of which 277(53.8%) were from other parts of Zhejiang Province and 238(46.2%) were from other provinces in China. Anhui, Jiangxi and Sichuan were among top three provinces which were the source of ecdemic multidrug-resistant tuberculosis cases. Three districts including Xiaoshan, Shangcheng and Linping districts had the most cases in Hangzhou. The proportion of ecdemic multidrug-resistant tuberculosis cases in Binjiang, Xiaoshan, Qiantang and Linping districtalso exceeded 30% of total cases., Conclusions: Multidrug-resistant tuberculosis prevalence has been declining in Hangzhou. Migrant population contributed to a significant potion of cases in Hangzhou. Interventions should be tailed to local and migrant residents., (© 2024. The Author(s).)

Background: Multidrug- or rifampicin-resistant tuberculosis (TB; MDR/RR-TB) is a significant public health threat. However, the mechanisms involved in its transmission in Sichuan, China are unclear. To provide a scientific basis for MDR/RR-TB control and prevention, we investigated the drug-resistance characteristics, genetic diversity, and transmission dynamics and analyzed the demographic and clinical characteristics of patients to identify risk factors for the acquisition of MDR/RR-TB in Sichuan, Western China., Methods: Whole-genome sequencing was performed using a sample comprised of all MDR/RR-TB strains isolated from patients with pulmonary TB (≥ 15 years) at the 22 surveillance sites in Sichuan province between January 2019 and December 2021, to analyze genotypic drug resistance and genetic diversity. Moreover, we performed statistical analyses of the epidemiological characteristics and risk factors associated with the transmission dynamics of MDR/RR-TB., Results: The final analysis included 278 MDR/RR TB strains. Lineage 2.2, the major sub-lineage, accounted for 82.01% (228/278) of isolates, followed by lineage 4.5 (9.72%, 27/278), lineage 4.4 (6.83%, 19/278), and lineage 4.2 (1.44%, 4/278). The drug resistance rates, ranging from high to low, were as follows: isoniazid (229 [82.37%]), streptomycin (177 [63.67%]), ethambutol (144 [51.80%]), pyrazinamide (PZA, 119 [42.81%]), fluoroquinolones (FQs, 93 [33.45%]). Further, the clofazimine, bedaquiline, and delamanid resistance rates were 2.88, 2.88, and 1.04%, respectively. The gene composition cluster rate was 32.37% (90/278). In addition, 83.81% (233/278) of MDR/RR-TB cases were determined to be likely caused by transmission. Finally, patients infected with lineage two strains and strains with the KatG S315T amino acid substitution presented a higher risk of MDR/RR-TB transmission., Conclusion: Transmission plays a significant role in the MDR/RR-TB burden in Sichuan province, and lineage 2 strains and strains harboring KatG S315T have a high probability of transmission. Further, high levels of FQ and PZA drug resistance suggest an urgent need for drug susceptibility testing prior to designing therapeutic regimens. New anti-TB drugs need to be used standardly and TB strains should be regularly monitored for resistance to these drugs., (© 2024. The Author(s).)

Globally, the prevalence of multidrug-resistant tuberculosis (MDR-TB) has been increasing recently. This is a major public health concern, as MDR-TB is more difficult to treat and has poorer outcomes compared to drug-sensitive tuberculosis. The main objective of the study was to identify risk factors for recurrent multidrug-resistant tuberculosis, at Alert Specialized Hospital, Addis Ababa, by using different parametric shared frailty models. From January 2016 to December 2021, a retrospective study was conducted on MDR-TB patients at Alert Specialized Hospital in Addis Ababa. The data for the study were collected from the medical records of MDR-TB patients at the hospital during this time period. Gamma and inverse-Gaussian shared frailty models were used to analyze the dataset, with the exponential, Weibull, and lognormal distributions included as baseline hazard functions. The data were analyzed using R statistical software. The median recurrence time of the patients was 12 months, and 149 (34.3%) had recurrences. The clustering effect was statistically significant for multiple drug-resistant tuberculosis patients' recurrence. According to the Weibull-Inverse-Gaussian model, factors that reduced time to MDR-TB recurrence included lower weight (ɸ = 0.944), smoking (ɸ = 0.045), alcohol use (ɸ = 0.631), hemoptysis (ɸ = 0.041), pneumonia (ɸ = 0.564), previous anti-TB treatment (ɸ = 0.106), rural residence (ɸ = 0.163), and chronic diseases like diabetes (ɸ = 0.442) were associated with faster recurrence. While, higher education (ɸ = 3.525) and age (ɸ = 1.021) extended time to recurrence. For weight increment, smokers and alcohol users, clinical complications of hemoptysis and pneumonia, patients with pulmonary disease who had a history of previous anti-TB treatment, and being rural residents are prognostic factors. There was a significant clustering effect at the Alert Specialized Hospital in Addis Ababa, Ethiopia. The Weibull-Inverse Gaussian Shared Frailty Model was chosen as the best model for predicting the time to recurrence of MDR-TB., (© 2024. The Author(s).)

Little is known regarding the relationship between common comorbidities in persons with tuberculosis (TB) (including human immunodeficiency virus [HIV], diabetes, and hepatitis C virus [HCV]) and post-TB mortality. We conducted a retrospective cohort study among persons who initiated treatment for rifampicin-resistant or multi/extensively drug-resistant (RR or M/XDR) TB reported to the country of Georgia's TB surveillance during 2009-2017. Exposures included HIV serologic status, diabetes, and HCV status. Our outcome was all-cause post-TB mortality determined by cross-validating vital status with Georgia's death registry through November 2019. We estimated adjusted hazard rate ratios (aHR) and 95% confidence intervals (CI) of post-TB mortality among participants with and without comorbidities using cause-specific hazard regressions. Among 1032 eligible participants, 34 (3.3%) died during treatment and 87 (8.7%) died post-TB treatment. The median time to post-TB death was 21 months (interquartile range 7-39) after TB treatment. After adjusting for confounders, the hazard rates of post-TB mortality were higher among participants with HIV co-infection (aHR = 3.74, 95%CI 1.77-7.91) compared to those without HIV co-infection. In our cohort, post-TB mortality occurred most commonly in the first 3 years post-TB treatment. Linkage to care for common TB comorbidities post-treatment may reduce post-TB mortality rates., (© 2024. The Author(s).)

Drug-resistant tuberculosis (TB) is estimated to cause 13% of all antimicrobial resistance-attributable deaths worldwide and is driven by both ongoing resistance acquisition and person-to-person transmission. Poor outcomes are exacerbated by late diagnosis and inadequate access to effective treatment. Advances in rapid molecular testing have recently improved the diagnosis of TB and drug resistance. Next-generation sequencing of Mycobacterium tuberculosis has increased our understanding of genetic resistance mechanisms and can now detect mutations associated with resistance phenotypes. All-oral, shorter drug regimens that can achieve high cure rates of drug-resistant TB within 6-9 months are now available and recommended but have yet to be scaled to global clinical use. Promising regimens for the prevention of drug-resistant TB among high-risk contacts are supported by early clinical trial data but final results are pending. A person-centred approach is crucial in managing drug-resistant TB to reduce the risk of poor treatment outcomes, side effects, stigma and mental health burden associated with the diagnosis. In this Review, we describe current surveillance of drug-resistant TB and the causes, risk factors and determinants of drug resistance as well as the stigma and mental health considerations associated with it. We discuss recent advances in diagnostics and drug-susceptibility testing and outline the progress in developing better treatment and preventive therapies., (© 2024. Springer Nature Limited.)

US-bound immigrants and refugees undergo a mandatory overseas medical examination that includes tuberculosis screening; this exam is not routinely required for temporary visitors applying for non-immigrant visas (NIV) to visit, work, or study in the United States. US health departments and foreign ministries of health report tuberculosis cases in travelers to Centers for Disease Control and Prevention Quarantine Stations. We reviewed cases reported to this passive surveillance system from January 2011 to June 2016. Of 1252 cases of tuberculosis in travelers reported to CDC, 114 occurred in travelers with a long-term NIV. Of these, 83 (73%) were infectious; 18 (16%) with multidrug-resistant tuberculosis (MDR TB) and one with extensively drug-resistant tuberculosis (XDR TB). We found evidence that NIV holders are diagnosed with tuberculosis disease in the United States. Given that long-term NIV holders were over-represented in this data set, despite the small proportion (4%) of overall non-immigrant admissions they represent, expanding the US overseas migration health screening program to this population might be an efficient intervention to further reduce tuberculosis in the United States., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objectives: This study investigated the transmission patterns of tuberculosis (TB) and its associated risk factors in Hunan province to inform the development of prevention and control strategies in the region., Methods: An 8-year retrospective population-based genomic epidemiological study was conducted. Genomic clusters were defined using distance thresholds of 12-single-nucletide-polymorphisms. Risk factors associated with TB transmission were analyzed using logistic regression model. Kernel Density analysis was used to locate hotspots where transmission occurred., Results: Among 2649 TB cases included in this study, 275 clusters were identified, with an overall clustering rate of 24.7% (654/2649). Nearly 95% (620/654) of clustered strains were isolated from the same county. Of the 275 clusters, 23 (8.4%, 23/275) had differences in drug-resistant profiles, with FQs resistance mutations occurring most frequently (52.2%, 12/23). Multivariate analysis identified male TB patients, those aged 30-60 years, ethnic minorities, nonfarmers, retreated TB patients, and individuals infected with MDR/RR-TB as independent risk factors for TB transmission (P < 0.05). Kernel density analysis showed that among the 5 drug-resistant surveillance sites, Leiyang had the highest clustering rate, followed by Yongshun, Qidong, Hecheng, and Taojiang., Conclusion: Recent transmission in the region is predominantly occurring within counties. The risk factors related to TB transmission and the hotspots where transmission occurs can provide a scientific basis for the formulation of targeted TB prevention and control strategies., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Rationale: Isoniazid-resistant tuberculosis (Hr-TB) is often overlooked in diagnostic algorithms because of reliance on first-line molecular assays testing only for rifampicin resistance. Objectives: To determine the prevalence, outcomes, and molecular mechanisms associated with rifampin-susceptible, isoniazid-resistant TB (Hr-TB) in the Eastern Cape, South Africa. Methods: Between April 2016 and October 2017, sputum samples were collected from patients with rifampin-susceptible TB at baseline and at Weeks 7 and 23 of drug-susceptible TB treatment. We performed isoniazid phenotypic and genotypic drug susceptibility testing, including FluoroTypeMTBDR, Sanger sequencing, targeted next-generation sequencing, and whole-genome sequencing. Results: We analyzed baseline isolates from 766 patients with rifampin-susceptible TB. Of 89 patients (11.7%) who were found to have Hr-TB, 39 (44%) had canonical katG or inhA promoter mutations; 35 (39%) had noncanonical katG mutations (including 5 with underlying large deletions); 4 (5%) had mutations in other candidate genes associated with isoniazid resistance. For 11 (12.4%), no cause of resistance was found. Conclusions: Among patients with rifampin-susceptible TB who were diagnosed using first-line molecular TB assays, there is a high prevalence of Hr-TB. Phenotypic drug susceptibility testing remains the gold standard. To improve the performance of genetic-based phenotyping tests, all isoniazid resistance-associated regions should be included, and such tests should have the ability to identify underlying mutations.

Introduction: Very few studies have been devoted to extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis (TB) in Gabon., Aim: The aim of the present study is to present the epidemiology of pre-XDR and XDR TB and the evolution over time of patients with multidrug-resistant TB., Methods: This retrospective study covered the activities from 2019 to 2022 of the Nkembo anti-tuberculosis center., Results: Fifteen patients were eligible, including 11 (73.3%) pre-XDR patients and 4 (26.7%) XDR-TB patients. Three (20.0%) patients had HIV/TB co-infection. The sample consisted of 7 men (46.7%) and 8 women (53.3%), a sex ratio (M/F) of 0.87. The average age was 35.6 years, and the median 34 years, with extremes of 23 and 60 years. Eight patients (53.3%) represented new cases of pre-XDR or XDR-TB tuberculosis. The majority (60%; n=9) came from deprived neighborhoods with widespread promiscuity. The therapeutic success rate among pre-XDR patients was 4 (36.4%) versus 2 (50.0%) among XDR-TB patients. Reported mortality occurred 5 (33.3%) patients during treatment, including 3 pre-XDR and 2 XDR-TB patients. In all cases, they died before the end of the first trimester of follow-up., Conclusion: The high frequency of primary pre-extensively drug-resistant tuberculosis underscores the pervasiveness of resistance to anti-tuberculosis drugs and underlines a pressing need for detection of contact cases and early treatment., (Copyright © 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: Rifampicin-resistant pulmonary tuberculosis (RR-PTB) presents a significant threat to global public health security. China bears a substantial burden of RR-PTB cases globally, with Guizhou Province experiencing particularly alarming trends, marked by a continual increase in patient numbers. Understanding the population characteristics and treatment modalities for RR-PTB is crucial for mitigating morbidity and mortality associated with this disease., Methods: We gathered epidemiological, diagnostic, and treatment data of all RR-PTB cases recorded in Guizhou Province from January 1, 2017 to December 31, 2023. Utilizing composition ratios as the analytical metric, we employed Chi-square tests to examine the spatiotemporal distribution patterns of RR-PTB patients and the evolving trends among different patient classifications over the study period., Results: In our study, 3396 cases of RR-PTB were analyzed, with an average age of 45 years. The number of RR-PTB patients rose significantly from 176 in 2017 to 960 in 2023, peaking notably among individuals aged 23-28 and 44-54, with a rising proportion in the 51-80 age group (P < 0.001). Since 2021, there has been a notable increase in the proportion of female patients. While individuals of Han ethnic group comprised the largest group, their proportion decreased over time (P < 0.001). Conversely, the Miao ethnicity showed an increasing trend (P < 0.05). The majority of patients were farmers, with their proportion showing an upward trajectory (P < 0.001), while students represented 4.33% of the cases. Geographically, most patients were registered in Guiyang and Zunyi, with a declining trend (P < 0.001), yet household addresses primarily clustered in Bijie, Tongren, and Zunyi. The proportion of floating population patients gradually decreased, alongside an increase in newly treated patients and those without prior anti-tuberculosis therapy. Additionally, there was a notable rise in molecular biological diagnostic drug sensitivity (real-time PCR and melting curve analysis) (P < 0.001). However, the cure rate declined, coupled with an increasing proportion of RR-PTB patients lost to follow-up and untreated (P < 0.05)., Conclusions: Enhanced surveillance is crucial for detecting tuberculosis patients aged 23-28 and 44-54 years. The distribution of cases varies among nationalities and occupations, potentially influenced by cultural and environmental factors. Regional patterns in RR-PTB incidence suggest tailored prevention and control strategies are necessary. Despite molecular tests advances, challenges persist with low cure rates and high loss to follow-up. Strengthening long-term management, resource allocation, and social support systems for RR-PTB patients is essential., (© 2024. The Author(s).)

Tuberculosis has posed a serious threat to human health. It is imperative to investigate the geographic prevalence of tuberculosis and medication resistance, as this information is essential for informing strategies for its prevention and treatment. Drug resistance was identified using a proportion method. Drug-resistant genes and pathways were predicted using whole genome sequencing. The drug resistance range of bedaquiline was identified using the microporous plate two-fold dilution method, and drug resistance genes were studied using sequencing. The study revealed that 19.99% of the tuberculosis cases had multidrug resistance. The genes of M. tuberculosis are predominantly involved in the synthesis of ABC transporters, two-component systems, and bacterial secretion systems, as well as in energy production and conversion, and lipid transport and metabolism. The genes encode for 82.45% of carbohydrate-related enzymes such as glycoside hydrolases, glycosyl transferases, and carbohydrate esterases. The minimum inhibitory concentration (MIC) of bedaquiline against clinical strains was approximately 0.06 μg/mL, with identified mutations in drug-resistant genes Rv0678, atpE, and pepQ, specifically V152A, P62A, and T222N, respectively. The multidrug resistance tuberculosis development was attributed to the strong medication resistance exhibited. It was concluded that tuberculosis had presented a high level of drug resistance. Phenotypic resistance was related to genes, existing potential genetic resistance in M. tuberculosis. Bedaquiline was found to possess effective antibacterial properties against M. tuberculosis., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright: © 2024 Peng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To provide valuable insights for targeted interventions and resource allocation, our analysis delved into the multifaceted burden, trends, risks, and projections of multi drug resistant tuberculosis (MDR-TB)., Methods: This research employed data from the Global Burden of Disease (GBD) 2019 dataset, which used a comparative risk assessment to quantify the disease burden resulting from risk factors. Initially, this database was utilized to extract details concerning the disability-adjusted life years (DALYs), mortality, incidence, and the number of individuals afflicted by MDR-TB. Subsequently, regression analyses were conducted using the Joinpoint program to figure average annual percent change (AAPC) to ascertain the trend. Thirdly, the age-period-cohort model (APCM) was adopted to analyze evolutions in incidence and mortality. Finally, utilizing the Nordpred model within R software, we projected the incidence and mortality of MDR-TB from 2020 to 2030., Results: MDR-TB remained a pressing global health concern in regions with lower socio-demographic indexes (SDI), where the AAPC in DALYs topped 7% from 1990 to 2019. In 2019, the cumulative DALYs attributed to MDR-TB tallied up to 4.2 million, with India, the Russian Federation, and China bearing the brunt. Notably, the incidence rates have shown a steadfast presence over the past decade, and a troubling forecast predicts an uptick in these areas from 2020 to 2030. Additionally, the risk of contracting MDR-TB grew with advancing age, manifesting most acutely among men aged 40+ in lower SDI regions. Strikingly, alcohol consumption had been identified as a significant contributor, surpassing the impacts of smoking and high fasting plasma glucose, leading to 0.7 million DALYs in 2019., Conclusions: A robust strategy is needed to end tuberculosis (TB) by 2030, especially in lower SDI areas., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Song, Tian, Song, Guo, Lin and Pan.)

Objective: To explore the direct economic burden and factors affecting out-of-pocket direct costs of multidrug-/rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB) patients in Jiangsu Province. Methods: MDR/RR-PTB patients diagnosed and treated at 13 municipal tuberculosis (TB)-designated hospitals in Jiangsu Province between January 1, 2021, and December 31, 2022, were included, and basic information and direct economic costs were obtained through questionnaires and hospital information systems. Stepwise multiple linear regression was used to analyze the factors influencing patients' out-of-pocket direct costs. Results: The age of the 233 MDR/RR-PTB patients was (44.04±15.64) years. The M ( Q 1 , Q 3 ) direct medical expense of the patients was 134 051.00 (98 934.01,163 205.73) Yuan, of which the M ( Q 1 , Q 3 ) reimbursement by health insurance or policy reduction was 100 462.10 (78 120.00,130 816.00) Yuan, and the M ( Q 1 , Q 3 ) out-of-pocket direct medical expense was 21 694.62 (14 734.83,37 813.00) Yuan. The M ( Q 1 , Q 3 ) direct non-medical expense was 4 971.00 (3 138.00,7 870.00) Yuan. Age, registered residence location, TB resulting in divorce or separation from spouse or partner, drug resistance test results, and treatment regimens were the influencing factors associated with out-of-pocket direct costs for MDR/RR-PTB patients. Conclusions: The direct economic burden caused by MDR/RR-PTB in Jiangsu Province is heavy. It is necessary to emphasize psychological guidance and care for MDR/RR-PTB patients, improve the diagnosis, treatment, and management of MDR/RR-PTB, and effectively reduce the economic burden of MDR/RR-PTB patients.

Tuberculosis is a global public health concern. Earlier reports suggested the emergence of high rates of drug resistant tuberculosis in Egypt. This study included 102 isolates of Mycobacterium tuberculosis collected from two reference laboratories in Cairo and Alexandria. All clinical isolates were sub-cultured on Löwenstein-Jensen medium and analyzed using both BD BACTEC MGIT 960 SIRE Kit and standard diffusion disk assays to identify the antibiotic sensitivity profile. Extracted genomic DNA was subjected to whole genome sequencing (WGS) using Illumina platform. Isolates that belong to lineage 4 represented > 80%, while lineage 3 represented only 11% of the isolates. The percentage of drug resistance for the streptomycin, isoniazid, rifampicin and ethambutol were 31.0, 17.2, 19.5 and 20.7, respectively. Nearly 47.1% of the isolates were sensitive to the four anti-tuberculous drugs, while only one isolate was resistant to all four drugs. In addition, several new and known mutations were identified by WGS. High rates of drug resistance and new mutations were identified in our isolates. Tuberculosis control measures should focus on the spread of mono (S, I, R, E)- and double (S, E)-drug resistant strains present at higher rates throughout the whole Nile Delta, Egypt., (© 2024. The Author(s).)

Introduction: Chest X-ray (CXR) remains one of the tools used in diagnosing tuberculosis (TB). However, few studies about such tools exist, specifically in children in Indonesia. We aim to investigate and compare the CXR findings of children with pulmonary drug-resistant TB (DR-TB) and drug-sensitive TB (DS-TB) that could help in the evaluation and management of TB cases in children., Methods: Retrospective analysis with cross-sectional approach was conducted in children (<18 years old) diagnosed with pulmonary DR-TB and DS-TB from January 2018 to December 2021. Documented data were collected from the Paediatric Respirology Registry and Tuberculosis Information System at Dr. Hasan Sadikin General Hospital Bandung. Characteristics of children, CXR findings, and TB severity were assessed and compared using the chi-square and Fisher's exact tests with significance levels set at p value <0.05., Results: Sixty-nine children (DR-TB 31 children vs. DS-TB 38 children) were assessed. Of the 31 children with DR-TB, 65% were classified as multidrug-resistant TB (MDR-TB), followed by rifampicin-resistant TB (RR-TB), pre-extensively drug-resistant TB (pre-XDR-TB), and extensively drug-resistant TB (XDR-TB). The most common CXR findings in DR-TB are consolidation (68%), fibrosis (42%), and cavity (29%), whereas in DS-TB, it is pleura effusion (37%). Severe TB accounts for 50% of DR-TB (p = 0.008)., Conclusions: Consolidation, fibrosis, cavities, and findings of severe TB are most common in DR-TB. Pleural effusion is the most common in DS-TB. These findings have the potential to be considered in further examination of children with pulmonary DR-TB and DS-TB; hence, more extensive studies are needed to confirm these results., (© 2024 The Author(s). The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Competing Interests: JF has received grant funding from the Stop TB Partnership's Global Drug Facility to support the rollout of child friendly formulations of second-line drugs. JP has received funding support from the Roe Green International Scholar's Fund. All other authors declare no competing interests. This work was funded by a grant from the Stop TB Partnership's Global Drug Facility.

Objectives: India's projected silica-dust-exposed workers will be 52 million at the end of 2025. The elimination of tuberculosis (TB) is also targeted in India by 2025. Scientists in India have already pointed out that unless silicosis is controlled, the said elimination will be difficult to achieve., Methods and Results: This study provides evidence of an increasing incidence of tuberculosis (TB) including multidrug-resistant TB (MDR-TB) with mortality owing to treatment failure among the silica dust-exposed workers compared to their unexposed counterpart. It was also observed that TB as well as MDR-TB were directly proportional to the dose and/or duration of silica dust exposure (progression of silica-dust induced lung damage). This means the occurrence of both TB and MDR-TB is lowest in the unexposed group, moderate in the radiologically negative but silica dust-exposed group (subradiological silicosis owing to moderate exposure), and highest in the radiologically confirmed silicotic workers (maximally exposed group). Because India has a huge burden of silicosis cases, the said cases are vulnerable to pulmonary TB, including MDR-TB. The study indicates there will be an emergence of MDR-TB among the silica dust-exposed workers unless appropriate intervention measures are initiated with immediate effect. Failure to do so, it will probably lead to a silent epidemic of silicotuberculosis in India shortly., Conclusions: It is important to have tools to detect silicosis cases quickly and at an early stage to identify a vulnerable population and adopt an effective intervention measure., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The National Tuberculosis Elimination Programme (NTEP) of the Government of India has strived to control tuberculosis (TB) in the country through various interventions. Understanding the trends of resistance patterns may provide insights into the effectiveness of TB control activities in the country., Methods: A total of 31,144 clinical samples were received from 2013 to 2022 from presumptive drug-resistant TB patients. All the specimens were decontaminated and subjected to the line probe assay for detection of resistance to rifampicin and isoniazid. Mycobacterium tuberculosis (MTB) was detected in 28,814 samples. Autoregressive integrated moving average model (ARIMA) was fitted to assess the trend over time., Results: A decreasing trend in multi-drug resistant TB from 19 % in 2013 to 4 % in 2022 was seen. A decreasing trend in rifampicin monoresistance from 11.2 % in 2013 to 1.5 % in 2022 was seen, though there was an increase in resistance in 2017. No significant decreasing trends were seen in the proportion of isoniazid monoresistance from 8.3 % in 2013 to 7 % in 2022., Conclusion: The findings are encouraging, and to a considerable extent, affirm that India is well on track with regard to the goal of TB elimination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Background: Tuberculosis (TB), one of the deadliest infectious diseases globally, is increasingly exacerbated in China by the emergence of resistant Mycobacterium tuberculosis (MTB) strains. Drug-resistant TB, including mono-drug-resistant TB, multidrug-resistant TB (MDR-TB), and extensively drug-resistant TB (XDR-TB), presents significant public health challenges., Methods: We conducted a systematic literature review from January 2010 to February 2024 using databases such as PubMed, Embase, Web of Science, and Google Scholar. Our focus was on empirical data related to drug resistance patterns in newly diagnosed TB cases. Non-empirical studies were excluded through meticulous filtering. For the meta-analysis, we used Review Manager (RevMan) 5.2 and assessed evidence quality using the Newcastle-Ottawa Scale (NOS)., Results: Our search strategy identified 40 studies that met the inclusion criteria, encompassing a total sample size of 87,667 participants. Among new TB cases, the estimated prevalence of MDR-TB in China was 6.9% (95% CI: 5.6-8.1%). Prevalence rates for mono-drug resistance to first-line anti-TB medications were as follows: isoniazid at 18.2% (95% CI: 16.4-20.6%), rifampicin at 10.5% (95% CI: 8.6-12.8%), and ethambutol at 5.7% (95% CI: 4.1-7.3%). The prevalence of streptomycin resistance, a former first-line anti-TB drug, was 17.1% (95% CI: 14.6-19.1%). The prevalence of other types of mono-drug resistance was 15.2% (95% CI: 13.9-17.3%), and for XDR-TB, it was 0.9% (95% CI: 0.6-1.4%)., Conclusions: The high prevalence of drug-resistant TB in China poses a significant public health challenge. There is an urgent need for targeted interventions and continued surveillance to combat the spread of drug-resistant TB., Competing Interests: Conflicts of Interest The authors declare no conflict of interest, financial or otherwise., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Tuberculosis (TB) is an emerging threat to the survival of elephants in Nepal. We investigated the lung tissue samples from nine elephants that died from 2019 to 2022 in Nepal using culture, conventional PCR, and loop-mediated isothermal amplification (LAMP) and then performed genotyping of five PCR-positive isolates to understand the possible transmission dynamics of Mycobacterium tuberculosis (Mtb). Results showed that two-thirds (6/9) of elephants were confirmed to be infected from Mtb by LAMP, 5/9 by PCR, and 4/9 by culture. Genotyping of Mtb isolates showed that elephants were infected with the Indo-Oceanic and Beijing lineages including an isoniazid-resistant Beijing lineage. MIRU-VNTR-based phylogeny, gyrA, and katG sequencing showed the possibility of ongoing transmission of Indo-Oceanic lineages and likely transmission of the drug-resistant Beijing lineage from human to elephant. Implementation of comprehensive surveillance and preventive measures are urgently needed to address this zoonotic disease and protect elephants from TB in Nepal., Competing Interests: Declaration of competing interest All authors have no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: COVID-19 pandemic has disrupted tuberculosis (TB) services in many countries, but the impacts on sites of involvement, drug susceptibility, smear positivity and clinical outcomes, and clinical outcomes of co-infection with influenza and COVID-19 remain unclear., Methods: Descriptive epidemiological study using episode-based and patient unique data of tuberculosis from Hospital Authority's territory-wide electronic medical record database, comparing baseline (January 2015-December 2019) and COVID-19 period (January 2020-December 2022), followed by univariate and multivariate analyses. Effects of co-infection with influenza and COVID-19 were investigated., Results: The study included 10,473 episodes of laboratory-confirmed TB, with 6818 in baseline period and 3655 during COVID-19 period. During COVID-19 period, TB patients had a lower proportion of smear positivity (49.2 % vs 54.7 %, P < 0.001), and fewer cases of extrapulmonary TB (7.0 % vs 8.0 %, P = 0.078) and multidrug resistant TB (1.0 % vs 1.6 %, P = 0.020). Mortality was higher in TB patients with COVID-19 coinfection (OR 1.7, P = 0.003) and influenza coinfection (OR 2.6, P = 0.004). During COVID-19 period, there were higher rates of treatment delay (20.5 % vs 15.5 %, P < 0.001) and episodic death (15.1 % vs 13.3 %, P = 0.006). Factors associated with higher mortality included age ≥ 70 years (OR 7.24), treatment delay (OR 2.16), extrapulmonary TB (OR 2.13). smear positivity (OR 1.71) and Charlson comorbidity index score ≥ 3 (OR 1.37). Higher mortality was observed with co-infection by influenza (OR 1.18) and COVID-19 (OR 1.7)., Conclusions: The epidemiology and outcomes of TB were changed during COVID-19 period. Mortality was higher during COVID-19 period and with co-infection by influenza and COVID-19., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Multidrug -resistant tuberculosis (MDRTB) is a serious threat to mankind. India has the highest number of MDRTB cases, although majority remain undiagnosed due to inadequate diagnostic infrastructure, leading to increased community transmission and mortality. This one-year observational retrospective study highlighted the effectiveness of the National Tuberculosis Elimination Program (NTEP) for prompt detection of drug-resistant TB by GeneXpert MTB/RIF assay and revealed its associated clinico-epidemiological factors. The overall detection rates of MTB and RRTB were 20.70 % and 20.86 % respectively. The pediatric population had 7.69 % rifampicin resistance, and HIV was strongly associated with the development of TB and RRTB (P < 0.01)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Drug-resistant tuberculosis (DR-TB) threatens to derail tuberculosis control efforts, particularly in Africa where the disease remains out of control. The dogma that DR-TB epidemics are fueled by unchecked rates of acquired resistance in inadequately treated or non-adherent individuals is no longer valid in most high DR-TB burden settings, where community transmission is now widespread. A large burden of DR-TB in Africa remains undiagnosed due to inadequate access to diagnostic tools that simultaneously detect tuberculosis and screen for resistance. Furthermore, acquisition of drug resistance to new and repurposed drugs, for which diagnostic solutions are not yet available, presents a major challenge for the implementation of novel, all-oral, shortened (6-9 months) treatment. Structural challenges including poverty, stigma, and social distress disrupt engagement in care, promote poor treatment outcomes, and reduce the quality of life for people with DR-TB. We reflect on the lessons learnt from the South African experience in implementing state-of-the-art advances in diagnostic solutions, deploying recent innovations in pharmacotherapeutic approaches for rapid cure, understanding local transmission dynamics and implementing interventions to curtail DR-TB transmission, and in mitigating the catastrophic socioeconomic costs of DR-TB. We also highlight globally relevant and locally responsive research priorities for achieving DR-TB control in South Africa., Competing Interests: Declaration of interests HC is a data and safety monitoring board member for the TRIAD study. AD is a Communities, Gender and Rights consultant for the Stop TB Partnership Secretariat, United Nations Office for Project Services. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: We sought to understand the impact of the initial COVID-19 mitigation strategies in 2020 on drug-resistant (DR) TB diagnoses in KwaZulu-Natal province (KZN), South Africa., Methods: We compared the number, spatial distribution, and characteristics of DR TB diagnoses before and after the initial COVID-19 lockdown on March 26th, 2020. Information on DR TB diagnoses was collected from the CONTEXT prospective cohort study and municipality characteristics were collected from Statistics South Africa. We used Bayesian conditional autoregressive models and relative-risk surface maps to examine spatial correlates and patterns of DR TB notifications., Results: Between October 2018 and February 2022, there were 693 individuals diagnosed with DR TB in KZN, South Africa. The rate of diagnoses per year was 274 and 155 prior and after to the initial lockdowns, respectively, corresponding to a 43 % decrease in the notification rate of cases. Compared to cases diagnosed before the lockdown, cases diagnosed after were less likely to have a fuel source for heating, piped water, a flush toilet, or own a phone (p-values≤0.02). Changes in notifications were not homogenously distributed, with predominantly rural northeastern and southwestern municipalities having significantly greater relative-risks after the lockdown., Conclusions: We found a reduction in the rate of DR TB diagnoses after the COVID-19 pandemic lockdowns and observed that individuals diagnosed after the lockdowns had worse living conditions, fewer household resources, and more adults living in their household compared to before the pandemic., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: A low body mass index (BMI) at the start of treatment for rifampicin- or multidrug-resistant tuberculosis (MDR/RR-TB) is associated with poor treatment outcomes and may contribute to delayed sputum culture conversion, thereby prolonging the period of potential transmission to others. Whether the relative importance of low BMI in predicting treatment outcomes differs by HIV status is unclear., Objectives: We evaluated the association between low BMI and two dependent variables, sputum culture conversion and end-of-treatment outcome, among patients receiving treatment for MDR/RR-TB in Lesotho, a setting with a high prevalence of HIV infection., Methods: Secondary data from a prospective cohort of patients initiating a longer (18-20 months) treatment containing bedaquiline and/or delamanid under routine programmatic conditions in Lesotho were analysed. Risk ratios and differences were adjusted for potential confounders using multivariable logistic regression, and estimates were stratified by HIV status., Results: Of 264 patients, 105 and 250 were eligible for culture conversion and end-of-treatment analyses, respectively. Seventy-one per cent of patients (74/105) experienced culture conversion within six months, while 74% (184/250) experienced a favourable end-of-treatment outcome. Low BMI was associated with a lower frequency of culture conversion at six months among those who were not living with HIV (relative risk [RR]: 0.50 [95% CI: 0.21, 0.79]); this association was attenuated among those living with HIV (RR: 0.88 [95% CI: 0.68, 1.23]). A low BMI was moderately associated with a lower frequency of treatment success (RR = 0.89 [95% CI: 0.77, 1.03]), regardless of HIV status., Conclusions: Low BMI was common and associated with the frequency of six-month culture conversion and end-of-treatment outcomes. The association with culture conversion was more pronounced among those not living with HIV. Addressing the myriad factors that drive low BMI in this setting could hasten culture conversion and improve end-of-treatment outcomes. This will require a multipronged approach focused on alleviating food insecurity and enabling prompt diagnosis and treatment of HIV and TB.

Isoniazid is an early bactericidal anti-tuberculosis (TB) agent and isoniazid mono-resistance TB is the most prevalent drug-resistant TB worldwide. Concerns exist regarding whether resistance to isoniazid would lead to delayed culture conversion and worst outcomes. From January 2008 to November 2017, adult culture-positive pulmonary TB patients receiving isoniazid, rifampicin, pyrazinamide, and ethambutol were identified through Taiwan Center for Disease Control database and were followed until the end of 2017. Primary outcomes included time to sputum culture conversion (SCC) within two months. Secondary outcomes included death and unfavourable outcomes at the end of 2nd month. A total of 37,193 drug-susceptible and 2,832 isoniazid monoresistant pulmonary TB patients were identified. Compared with no resistance, isoniazid monoresistance was not associated with a delayed SCC (HR: 0.99, 95% CI: 0.94─1.05, p  = 0.8145), a higher risk of 2-month mortality (HR: 1.19, 95% CI: 0.92─1.53, p  = 0.1884), and unfavourable outcomes at 2nd month (OR: 1.05, 95% CI: 0.97─1.14, p  = 0.2427). Isoniazid monoresistance was associated with delayed SCC (HR: 0.90, 95% CI: 0.83─0.98, p  = 0.0099) and a higher risk of unfavourable outcomes (OR:1.18, 95% CI: 1.05─1.32, p  = 0.0053) in patients aged between 20 and 65, and delayed SCC in patients without underlying comorbidities (HR: 0.90, 95% CI: 0.81─0.98, p  = 0.0237). Isoniazid mono-resistant TB had a comparable outcome with drug-susceptible TB at the end of the intensive phase. Healthy, and non-elderly patients were more likely to had culture persistence, raising concerns about disease transmission in these subgroups and warranting early molecular testing for isoniazid resistance.

Fluoroquinolones (FQ) are essential for the treatment of multidrug-resistant tuberculosis (MDR-TB). The FQ resistance (FQ-R) rate in MDR-TB in China and its risk factors remain poorly understood. We conducted a retrospective, population-based genomic epidemiology study of MDR-TB patients in Shanghai, China, from 2009 to 2018. A genomic cluster was defined as strains with genetic distances ≤ 12 single nucleotide polymorphisms. The transmitted FQ-R was defined as the same FQ resistance-conferring mutations shared by ≥ 2 strains in a genomic cluster. We used multivariable logistic regression analysis to identify the risk factors for drug resistance. Among the total 850 MDR-TB patients included in the study, 72.8% (619/850) were male, the median age was 39 (interquartile range 28, 55) years, 52.7% (448/850) were migrants, and 34.5% (293/850) were previously treated patients. Most of the MDR-TB strains belong to the Beijing lineage (91.7%, 779/850). Overall, the genotypic resistance rate of FQ was 34.7% (295/850), and 47.1% (139/295) FQ-R patients were in genomic clusters, of which 98 (33.2%, 98/295) were presumed as transmitted FQ-R. Patients with treatment-naïve (aOR = 1.84; 95% CI: 1.09, 3.16), diagnosed in a district-level hospital (aOR = 2.69; 95% CI: 1.56, 4.75), and streptomycin resistance (aOR = 3.69; 95% CI: 1.65, 9.42) were significantly associated with the transmission of FQ-R. In summary, the prevalence of FQ-R among MDR-TB patients was high in Shanghai, and at least one-third were transmitted. Enforced interventions including surveillance of FQ drug susceptibility testing and screening among MDR-TB before initiation of treatment were urgently needed.

Objectives: We investigated the genetic diversities and lineage-specific transmission dynamics of multidrug-resistant tuberculosis (MDR-TB), with the goal of determining the potential factors driving the MDR epidemics in China., Methods: We curated a large nationwide Mycobacterium tuberculosis ( M. tuberculosis ) whole genome sequence data set, including 1313 MDR strains. We reconstructed the phylogeny and mapped the transmission networks of MDR-TB across China using Bayesian inference. To identify drug-resistance variants linked to enhanced transmissibility, we employed ordinary least-squares (OLS) regression analysis., Result: The majority of MDR-TB strains in China belong to lineage 2.2.1. Transmission chain analysis has indicated that the repeated and frequent transmission of L2.2.1 plays a central role in the establishment of MDR epidemic in China, but no occurrence of a large predominant MDR outbreak was detected. Using OLS regression, the most common single nucleotide polymorphisms (SNPs) associated with resistance to isoniazid ( katG&#95;p.Ser315Thr and katG&#95;p.Ser315Asn ) and rifampicin ( rpoB&#95;p.Ser450Leu , rpoB&#95;p.His445Tyr , rpoB&#95;p.His445Arg , rpoB&#95;p.His445Asp , and rpoB&#95;p.His445Asn ) were more likely to be found in L2 clustered strains. Several putative compensatory mutations in rpoA , rpoC , and katG were significantly associated with clustering. The eastern, central, and southern regions of China had a high level of connectivity for the migration of L2 MDR strains throughout the country. The skyline plot showed distinct population size expansion dynamics for MDR-TB lineages in China., Conclusion: MDR-TB epidemic in China is predominantly driven by the spread of highly transmissible Beijing strains. A range of drug-resistance mutations of L2 MDR-TB strains displayed minimal fitness costs and may facilitate their transmission.

China, with the third largest share of global tuberculosis cases, faces a substantial challenge in its healthcare system as a result of the high burden of multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB). This study employs a genomic epidemiological approach to assess recent tuberculosis transmissions between individuals, identifying potential risk factors and discerning the role of transmitted resistant isolates in the emergence of drug-resistant tuberculosis in China. We conducted a population-based retrospective study on 5052 Mycobacterium tuberculosis (MTB) isolates from 70 surveillance sites using whole genome sequencing (WGS). Minimum spanning tree analysis identified resistance mutations, while epidemiological data analysis pinpointed transmission risk factors. Of the 5052 isolates, 23% (1160) formed 452 genomic clusters, with 85.6% (387) of the transmissions occurring within the same counties. Individuals with younger age, larger family size, new cases, smear positive, and MDR/RR were at higher odds for recent transmission, while higher education (university and above) and occupation as a non-physical workers emerged as protective factors. At least 61.4% (251/409) of MDR/RR-TB were likely a result of recent transmission of MDR/RR isolates, with previous treatment (crude OR =   2.77), smear-positive (cOR =   2.07) and larger family population (cOR = 1.13) established as risk factors. Our findings highlight that local transmission remains the predominant form of TB transmission in China. Correspondingly, drug-resistant tuberculosis is primarily driven by the transmission of resistant tuberculosis isolates. Targeted interventions for high-risk populations to interrupt transmission within the country will likely provide an opportunity to reduce the prevalence of both tuberculosis and drug-resistant tuberculosis.

Objective: Osteoarticular tuberculosis (OATB) is one of the most common forms of extrapulmonary tuberculosis; however, limited epidemiological data are available on this public health concern worldwide, especially in developing countries. This study aimed to analyze the clinical epidemiology and drug resistance characteristics of OATB cases in Hunan province which located in South-central China., Methods: We retrospectively enrolled OATB patients with Mycobacterium tuberculosis culture positive at Hunan Chest Hospital from January 2013 through March 31, 2022. The multiple demographic, clinical variables and drug susceptibility data of the patients were collected from the hospital's electronic patient records. Descriptive statistical methods, Chi-square test and logistic regression analysis were employed as statistical methods., Results: Of the 269 OATB cases, 197 (73.23%) were males, 206 (76.85%) were farmers; patients' ages ranged from 5 to 85 years, 57 (21.19%) aged at 20-29 years old and 52 (19.33%) aged at 60-69 years old. In terms of the disease, 177 (65.80%) had spinal TB with most occurrence in lumbar vertebrae (26.02%, 70/269), multiple spinal sites (18.96%, 51/269) and thoracic vertebrae (15.24%, 41/269). Outside of the spine, OATB mainly occurred in the lower limb (13.38%, 36/269). In terms of drug resistance, 40 (14.87%) and 72 (26.77%) were resistant to rifampicin (RFP) and isoniazid (INH) respectively; 38 (14.13%) were multi-drug resistant (MDR), and a total of 78 (29.00%) isolates were drug resistant. OATB patients aged 40-49 years old (compared to those aged ≥70 years) and from the west of Hunan province, China (compared to those from the center of Hunan) were at risk for developing RR/MDR (ORs were 5.057 and 4.942, respectively; 95% CIs were 1.009-25.342 and 1.458-16.750, respectively)., Conclusion: In South-central China, OATB mainly affected males, farmers and those aged 20-29 and 60-69 years old. Spinal TB is prone to occur in the lumbar and multiple spinal sites. The resistance situation of OATB was serious, and people aged 40-49 years old and patients from the west of Hunan were risk factors of RR/MDR. All these findings will help to improve the prevention, diagnosis and treatment strategies of OATB., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fang, Yang, Liu, Li, Sun, Liu, Yu, Xiang, Li, Guo, Li, Zhao, Zhao, Wan, Li, Yuan and Tan.)

Introduction. Proper management of multidrug-resistant tuberculosis is a prioritized strategy for tuberculosis control worldwide. Objective. To evaluate differences concerning demographic and clinical characteristics and programmatic indicators of Buenaventura patient cohort with confirmed diagnosis of multidrug-resistant tuberculosis, compared to those of the other municipalities from Valle del Cauca, Colombia, 2013-2016. Materials and methods. We conducted an analytical cohort study to compare records of patients older than 15 years with multidrug-resistant tuberculosis included in the Programa de Tuberculosis de Buenaventura (with para-aminosalicylic acid) versus the other municipalities of Valle del Cauca (without para-aminosalicylic). Results. Ninety-nine cases were recorded with a median age of 40 years (IQR = 26 - 53); in Buenaventura, 56% of the patients were women, while in the other municipalities, men predominated with 67%; 95% had health insurance. The most common comorbidity was diabetes (14%). Adverse reactions to antituberculosis medications in Buenaventura were 1.3 times more frequent than in the other municipalities (OR = 2.3; 95% CI = 0.993 - 5.568; p = 0.04). In Buenaventura, the mortality rate was 5% compared to the 15% reported in the other municipalities. Treatment failures were not reported in Buenaventura, but 35% did not continue with the follow-up. Treatment success was higher in Buenaventura (56 %). Conclusion. A strengthened program in Buenaventura presented better programmatic results than those from the other municipalities of Valle del Cauca. Access to molecular tests, availability of shortened treatments, and continuous monitoring to identify adverse reactions to antituberculosis medications are routes for all other control programs.

Background and Objectives: Drug resistant tuberculosis (DR-TB) remains a global challenge with about a third of the cases are not detected. With the recent advances in the diagnosis and treatment follow-up of DR-TB, there have been improvements with treatment success rates. However, there is limited evidence on the successful models of care that have consistently registered good outcomes. Our aim was to assess Ethiopia's experience in scaling up an ambulatory, decentralized model of care while managing multiple regimen transition processes and external shocks., Methods: This was a cross-sectional, mixed-method study. For the quantitative data, we reviewed routine surveillance data for the period 2009-2022 and collected additional data from publicly available reports. We then analyzed the data descriptively. Qualitative data were collected from program reports, quarterly presentations, minutes of technical working group meetings, and clinical review committee reports and analyzed thematically., Results: The number of DR-TB treatment initiating centers increased from 1 to 67, and enrollment increased from 88 in 2010 to 741 in 2019, but declined to 518 in 2022. A treatment success rate (TSR) of over 70% was sustained. The decentralized and ambulatory service delivery remained the core service delivery model. The country successfully navigated multiple regimen transitions, including the recently introduced six-month short oral regimen. Several challenges remain, including the lack of strong and sustainable specimen transportation system, lack of established systems for timely tracing and linking of missed DR-TB cases, and data quality issues., Conclusions: Ethiopia scaled up a decentralized ambulatory model of care, kept up to date with recent developments in treatment regimens, and maintained a high TSR, despite the influence of multiple external challenges. The recent decline in case notification requires a deeper look into the underlying reasons. The feasibility of fully integrating DR-TB treatment and follow up at community level should be explored further., Competing Interests: the authors have declared that no competing interests exist., (Copyright: © 2024 Tesema et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Antimicrobial resistance in Mycobacterium tuberculosis (MTB) poses a significant challenge to tuberculosis (TB) management worldwide. Rifampicin resistance (RR) has been associated with the rpoB gene mutation. No study was conducted in Tanzania to determine the commonest mutation. The inconsistent findings from various studies support the need to determine whether reported mutation patterns are applicable in our setting. We determined the frequency of rpoB gene mutation and factors associated with RR, which were detected using GeneXpert MTB/RIF assay., Methods: We conducted a retrospective cross-sectional study involving data from the National Tuberculosis and Leprosy Program database from 2020 to 2022 for cases investigated using GeneXpert MTB/RIF assay. Descriptive analysis was performed to determine the frequency of categorical variables. The chi-square test and logistic regression analysis assessed the relationship between the independent variables and outcome. The 95% confidence interval and a significance level of p<0.05 were used to assess the strength of association., Results: A total of 56,004 participants had a status of MTB and RR, where 38,705/56,004 (69.11%) were males. Probe E mutation (codon 529-533), 89/219 (40.64%) was predominant. Human immunodeficiency virus (HIV)-positive patients had a higher gene mutation, 134/10601 (1.26%) than HIV-negative, 306/45016 (0.68%) (p<0.001). Patients with both pulmonary and extra-pulmonary TB had about four times greater odds of developing rifampicin resistance (AOR 3.88, 95%CI: 1.80-8.32). RR was nearly nine times higher in previously treated patients than new patients (AOR 8.66, 95% CI: 6.97-10.76). HIV-positive individuals had nearly twice the odds of developing RR than HIV-negative individuals (AOR 1.91, 95%CI: 1.51-2.42)., Conclusion: The rate of RR was lower compared to other studies in Tanzania, with probe E mutations the most prevalent. Patients with disseminated TB, HIV co-infection and those with prior exposure to anti-TB had more risk of RR. The findings highlight the need to strengthen surveillance of multidrug-resistant TB among high risk patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Torokaa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Fluoroquinolone resistance is a major challenge in treating Multidrug-Resistant Tuberculosis globally. The GenoType MTBDRsl Ver 2.0, endorsed by the WHO, was used to characterize fluoroquinolone resistance. The fluoroquinolone resistance rates in the MDR-TB, Rifampicin-Resistant TB, and non-MDR-TB were 33%, 16.5%, and 5.4%, respectively. The most common mutation found in fluoroquinolone-resistant isolates was D94G (49.5%) in the gyrA gene. Of the 150 MDR-TB isolates, the prevalence of Extensively Drug-Resistant Tuberculosis and pre-XDR-TB was 1.33% and 30%, respectively. Among the 139 RR-TB isolates, pre-XDR-TB prevalence was 15.8%. The fluoroquinolone resistance rates were 5.12% among the 1230 isoniazid-monoresistant isolates. The study found that MDR-TB and RR-TB have higher risk of fluoroquinolone resistance than non-MDR tuberculosis. Rifampicin-resistant isolates with a mutation at codon S450L have a higher risk (RR = 12.96; 95%CI: 8.34-20.13) of developing fluoroquinolone resistance than isolates with mutations at other codons in the rpoB gene. Isoniazid-resistant isolates with a mutation at codon S315T have a higher risk (RR = 2.09; 95%CI: 1.25-3.50) of developing fluoroquinolone resistance. The study concludes that rapid diagnosis of fluoroquinolone resistance before starting treatment is urgently needed to prevent the spread and increase of resistance and to achieve better treatment outcomes in areas where it is higher., (© 2024. The Author(s).)

The Philippines is a high-incidence country for tuberculosis, with the increasing prevalence of multi- (MDR-TB) and extensively-drug (XDR-TB) resistant Mycobacterium tuberculosis strains posing difficulties to disease control. Understanding the genetic diversity of circulating strains can provide insights into underlying drug resistance mutations and transmission dynamics, thereby assisting the design of diagnostic tools, including those using next generation sequencing (NGS) platforms. By analysing genome sequencing data of 732 isolates from Philippines drug-resistance survey collections spanning from 2011 to 2019, we found that the majority belonged to lineages L1 (531/732; 72.5%) and L4 (European-American; n = 174; 23.8%), with the Manila strain (L1.2.1.2.1) being the most prominent (475/531). Approximately two-thirds of isolates were found to be at least MDR-TB (483/732; 66.0%), and potential XDR-TB genotypic resistance was observed (3/732; 0.4%), highlighting an emerging problem in the country. Genotypic resistance was highly concordant with laboratory drug susceptibility testing. By finding isolates with (near-)identical genomic variation, five major clusters containing a total of 114 isolates were identified: all containing either L1 or L4 isolates with at least MDR-TB resistance and spanning multiple years of collection. Closer inspection of clusters revealed transmission in prisons, some involving isolates with XDR-TB, and mutations linked to third-line drug bedaquiline. We have also identified previously unreported mutations linked to resistance for isoniazid, rifampicin, ethambutol, and fluoroquinolones. Overall, this study provides important insights into the genetic diversity, transmission and circulating drug resistance mutations of M. tuberculosis in the Philippines, thereby informing clinical and surveillance decision-making, which is increasingly using NGS platforms., (© 2024. The Author(s).)

Background: Tuberculosis (TB) is a major infectious disease with significant public health implications. Its widespread transmission, prolonged treatment duration, notable side effects, and high mortality rate pose severe challenges. This study examines the epidemiological characteristics of TB globally and across major regions, providing a scientific basis for enhancing TB prevention and control measures worldwide., Methods: The ecological study used data from the Global Burden of Disease (GBD) Study 2021. It assessed new incidence cases, deaths, disability-adjusted life years (DALYs), and trends in age-standardized incidence rates (ASIRs), mortality rates (ASMRs), and DALY rates for drug-susceptible tuberculosis (DS-TB), multidrug-resistant tuberculosis (MDR-TB), and extensively drug-resistant tuberculosis (XDR-TB) from 1990 to 2021. A Bayesian age-period-cohort model was applied to project ASIR and ASMR., Results: In 2021, the global ASIR for all HIV-negative TB was 103.00 per 100,000 population [95% uncertainty interval (UI): 92.21, 114.91 per 100,000 population], declining by 0.40% (95% UI: - 0.43, - 0.38%) compared to 1990. The global ASMR was 13.96 per 100,000 population (95% UI: 12.61, 15.72 per 100,000 population), with a decline of 0.44% (95% UI: - 0.61, - 0.23%) since 1990. The global age-standardized DALY rate for HIV-negative TB was 580.26 per 100,000 population (95% UI: 522.37, 649.82 per 100,000 population), showing a decrease of 0.65% (95% UI: - 0.69, - 0.57 per 100,000 population) from 1990. The global ASIR of MDR-TB has not decreased since 2015, instead, it has shown a slow upward trend in recent years. The ASIR of XDR-TB has exhibited significant increase in the past 30 years. The projections indicate MDR-TB and XDR-TB are expected to see significant increases in both ASIR and ASMR from 2022 to 2035, highlighting the growing challenge of drug-resistant TB., Conclusions: This study found that the ASIR of MDR-TB and XDR-TB has shown an upward trend in recent years. To reduce the TB burden, it is essential to enhance health infrastructure and increase funding in low-SDI regions. Developing highly efficient, accurate, and convenient diagnostic reagents, along with more effective therapeutic drugs, and improving public health education and community engagement, are crucial for curbing TB transmission., (© 2024. The Author(s).)

Background: Rifampicin resistant tuberculosis (RR-TB) poses a growing threat to individuals and communities. This study utilized a seasonal autoregressive integrated moving average (SARIMA) model to quantitatively predict the monthly incidence of RR-TB in Yunnan Province which could guide government health administration departments and the centers for disease control and prevention (CDC) in preventing and controlling the RR-TB epidemic., Methods: The study utilized routine surveillance reporting data from the infectious Disease Network Surveillance and Reporting System. Monthly incidence rates of RR-TB were collected from January 2019 to December 2022. A time series SARIMA model was used to predict the number of monthly RR-TB cases in Yunnan Province in 2023, and the model was validated using time series plots, seasonal and non-seasonal differencing, autocorrelation and partial autocorrelation analysis, and white noise tests., Results: From 2019 to 2022, the incidence of RR-TB decreases as the incidence of all TB decreases (P < 0.05). There was no significant change in the proportion of RR-TB among all TB cases, which remained within 2.5% (P>0.05). The time series decomposition shows that it presented obvious seasonality, periodicity and randomness after being decomposed. Time series analysis was performed on the original series after 1 non-seasonal difference and 1 seasonal difference, the ADF test showed P < 0.05. According to ACF and PACF, the SARIMA (1, 1, 1) (1, 1, 0) 12 model was chosen and statistically significant model parameter estimates (P < 0.05). The predicted seasonal trend of RR-TB incidence in 2019 to 2023 was similar to the actual data. The percentage accuracy in the prediction excesses 80% in 2019 to 2022 and is all within 95% CI. However there was a certain gap between the actual incidence and the predicted value in 2023, and the acutual incidence had increased by 12.4% compared to 2022. The percentage of accuracy in the prediction was only 70% in 2023., Conclusions: We found the incidence of RR-TB was based on that of all TB in Yunnan. The SARIMA model successfully predicted the seasonal incidence trend of RR-TB in Yunnan Province in 2019 to 2023, but the prediction precision could be influenced by factors such as new infectious disease outbreaks or pandemics, social issues, environmental challenges or other unknown risks. Hence CDCs should pay special attention to the post epidemic effects of new infectious disease outbreaks or pandemics, carry out monitoring and early warning, and better optimize disease prediction models., (© 2024. The Author(s).)

Background: The co-infection of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and tuberculosis (TB) poses a significant clinical challenge and is a major global public health issue. This study aims to elucidate the disease burden of HIV-TB co-infection in global, regions and countries, providing critical information for policy decisions to curb the HIV-TB epidemic., Methods: The ecological time-series study used data from the Global Burden of Disease (GBD) Study 2021. The data encompass the numbers of incidence, prevalence, mortality, and disability-adjusted life year (DALY), as well as age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and DALY rate for HIV-infected drug-susceptible tuberculosis (HIV-DS-TB), HIV-infected multidrug-resistant tuberculosis (HIV-MDR-TB), and HIV-infected extensively drug-resistant tuberculosis (HIV-XDR-TB) from 1990 to 2021. from 1990 to 2021. The estimated annual percentage change (EAPC) of rates, with 95% confidence intervals (CIs), was calculated., Results: In 2021, the global ASIR for HIV-DS-TB was 11.59 per 100,000 population (95% UI: 0.37-13.05 per 100,000 population), 0.55 per 100,000 population (95% UI: 0.38-0.81 per 100,000 population), for HIV-MDR-TB, and 0.02 per 100,000 population (95% UI: 0.01-0.03 per 100,000 population) for HIV-XDR-TB. The EAPC for the ASIR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.71 (95% CI: 1.92-7.59) and 13.63 (95% CI: 9.44-18.01), respectively. The global ASMR for HIV-DS-TB was 2.22 per 100,000 population (95% UI: 1.73-2.74 per 100,000 population), 0.21 per 100,000 population (95% UI: 0.09-0.39 per 100,000 population) for HIV-MDR-TB, and 0.01 per 100,000 population (95% UI: 0.00-0.03 per 100,000 population) for HIV-XDR-TB in 2021. The EAPC for the ASMR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.78 (95% CI: 1.32-8.32) and 10.00 (95% CI: 6.09-14.05), respectively., Conclusions: The findings indicate that enhancing diagnostic and treatment strategies, strengthening healthcare infrastructure, increasing access to quality medical care, and improving public health education are essential to combat HIV-TB co-infection., (© 2024. The Author(s).)

Background: This dual burden of tuberculosis (TB) and diabetes mellitus (DM) has become a global public health concern. This study aims to compare drug resistance in drug-resistant tuberculosis (DR-TB) patients with and without DM and analyse the risk factors of multidrug-resistant tuberculosis (MDR-TB)., Methods: A total of 893 DR-TB patients were admitted to Wenzhou Central Hospital between January 2018 and December 2022. After excluding 178 cases with incomplete clinical and laboratory data, 715 patients were included in the study. These patients were then categorized into two groups based on the presence of type 2 DM: the DM group (160 cases) and the non-DM group (555 cases). Demographic information, baseline clinical characteristics, laboratory and imaging test results, clinical diagnoses, and other relevant data were collected for analysis. Statistical analysis was conducted on demographic information, clinical parameters, drug resistance spectrum, and risk factors for multidrug resistance., Results: In both the DM and non-DM groups, the order of resistance to first-line anti-tuberculosis drugs is isoniazid, streptomycin, rifampicin, and ethambutol. There is no significant difference in the proportion of mono-resistant tuberculosis, polydrug-resistant tuberculosis, and multidrug-resistant tuberculosis between the two groups (P > 0.05). The prevalence of MDR-TB in both groups shows a downward trend between 2018 and 2022, but the trend is not statistically significant (P > 0.05). Among patients without DM, residence in rural areas, retreatment of tuberculosis, pulmonary cavity, and uric acid ≥ 346 µmol/L are identified as independent risk factors for MDR-TB. Among patients with DM, residence in rural areas, retreatment of tuberculosis, pulmonary cavity, and HbA1c ≥ 9.8% were identified as independent risk factors for MDR-TB., Conclusion: Isoniazid is the most resistant drug among DR-TB patients with and without DM. There is no statistically significant difference in drug resistance patterns between the two groups. Some progress has been made in the prevention and control of DR-TB in this area, but the effect is not very significant. There are differences in the risk factors of MDR-TB between patients with and without DM., (© 2024. The Author(s).)

For facilitating tuberculosis (TB) control, we used a whole-genome sequencing (WGS)-based approach to delineate transmission networks in a country with an intermediate burden of TB. A cluster was defined as Mycobacterium tuberculosis isolates with identical genotypes, and an outbreak was defined as clustered cases with epidemiological links (epi-links). To refine a cluster predefined using space oligonucleotide typing and mycobacterial interspersed repetitive unit variable tandem repeat typing, we analyzed one pansusceptible TB (C1) and three multidrug-resistant (MDR)-TB (C2-C4) clusters from different scenarios. Pansusceptible TB cluster (C1) consisting of 28 cases had ≤5 single nucleotide polymorphisms (SNPs) difference between their isolates. C1 was a definite outbreak, with cases attending the same junior high school in 2012. Three MDR-TB clusters (C2-C4) with distinct genotypes were identified, each consisting of 12-22 cases. Some of the cases had either ≤5 or ≤15 SNPs difference with clear or probable epi-links. Of note, even though WGS could effectively assist TB contact tracing, we still observed missing epi-links in some cases within the same cluster. Our results showed that thresholds of ≤5 and ≤15 SNPs difference between isolates were used to categorize definite and probable TB transmission, respectively. Furthermore, a higher SNP threshold might be required to define an MDR-TB outbreak. WGS still needs to be combined with classical epidemiological methods for improving outbreak investigations. Importantly, different SNP thresholds have to be applied to define outbreaks., Importance: TB is a chronic disease. Depending on host factors and TB burden, clusters of cases may continue to increase for several years. Conventional genotyping methods overestimate TB transmission, hampering precise detection of outbreaks and comprehensive surveillance. WGS can be used to obtain SNP information of M. tuberculosis to improve discriminative limitations of conventional methods and to strengthen delineation of transmission networks. It is important to define the country-specific SNP thresholds for investigation of transmission. This study demonstrated the use of thresholds of ≤5 and ≤15 SNPs difference between isolates to categorize definite and probable transmission, respectively. Different SNP thresholds should be applied while a higher cutoff was required to define an MDR-TB outbreak. The utilization of SNP thresholds proves to be crucial for guiding public health interventions, eliminating the need for unnecessary public health actions, and potentially uncovering undisclosed TB transmissions., Competing Interests: The authors declare no conflict of interest.

Objective: The burden of tuberculosis (TB) in migrant children and young people (CYP) is commonly overlooked, despite the increasing incidence of TB in migrant populations in the European region. This study aimed to examine the distribution and disease characteristics of TB among migrant and native-born CYP through analysis of data from the European Centre for Disease Prevention and Control (ECDC) surveillance system (TESSy)., Study Design: Retrospective database analysis., Methods: A retrospective database analysis was conducted on all CYP TB cases (0-17 years) reported to TESSy (1995-2017), exploring distribution, site of TB, and presence of MDR-TB using multivariate analysis in R statistical software., Results: Of the 73,176 CYP TB cases reported in the EU/EFTA (1995-2017), 24.4% (n = 17,879) occurred in migrant CYP and 75.6% (n = 55,297) occurred in native-born CYP. Migrant CYP were more likely (P < 0.001) to have pulmonary TB (OR: 1.90; 95% CI: 1.74-2.09) and unsuccessful treatment outcomes (OR: 2.05; 95% CI: 1.74-2.40) compared to native-born CYP. The proportion of extrapulmonary TB, compared to pulmonary TB across total CYP cases was higher than the existing evidence base., Conclusions: Overall, there were significant differences in the site of TB and treatment outcomes between migrant and native-born CYP. To improve outcomes, TB screening and detection practices should focus on facilitating care in migrant CYP. However, to better understand the implications of these findings on broader TB control, TB among CYP should be addressed more frequently in reports and research., (Copyright © 2024. Published by Elsevier Ltd.)

New tuberculosis (TB) drugs with little existing antimicrobial resistance enable a pan-TB treatment regimen, intended for universal use without prior drug-susceptibility testing. However, widespread use of such a regimen could contribute to an increasing prevalence of antimicrobial resistance, potentially rendering the pan-TB regimen ineffective or driving clinically problematic patterns of resistance. We developed a model of multiple sequential TB patient cohorts to compare treatment outcomes between continued use of current standards of care (guided by rifampin-susceptibility testing) and a hypothetical pan-TB approach. A pan-TB regimen that met current target profiles was likely to initially outperform the standard of care; however, a rising prevalence of transmitted resistance to component drugs could make underperformance likely among subsequent cohorts. Although the pan-TB approach led to an increased prevalence of resistance to novel drugs, it was unlikely to cause accumulation of concurrent resistance to novel drugs and current first-line drugs.

Background: The antibiotic bedaquiline is a key component of new WHO regimens for drug-resistant tuberculosis; however, predicting bedaquiline resistance from bacterial genotypes remains challenging. We aimed to understand the genetic mechanisms of bedaquiline resistance by analysing Mycobacterium tuberculosis isolates from South Africa., Methods: For this genomic analysis, we conducted whole-genome sequencing of Mycobacterium tuberculosis samples collected at two referral laboratories in Cape Town and Johannesburg, covering regions of South Africa with a high prevalence of tuberculosis. We used the tool ARIBA to measure the status of predefined genes that are associated with bedaquiline resistance. To produce a broad genetic landscape of M tuberculosis in South Africa, we extended our analysis to include all publicly available isolates from the European Nucleotide Archive, including isolates obtained by the CRyPTIC consortium, for which minimum inhibitory concentrations of bedaquiline were available., Findings: Between Jan 10, 2019, and July, 22, 2020, we sequenced 505 M tuberculosis isolates from 461 patients. Of the 64 isolates with mutations within the mmpR5 regulatory gene, we found 53 (83%) had independent acquisition of 31 different mutations, with a particular enrichment of truncated MmpR5 in bedaquiline-resistant isolates resulting from either frameshift mutations or the introduction of an insertion element. Truncation occurred across three M tuberculosis lineages, and were present in 66% of bedaquiline-resistant isolates. Although the distributions overlapped, the median minimum inhibitory concentration of bedaquiline was 0·25 mg/L (IQR 0·12-0·25) in mmpR5-disrupted isolates, compared with 0·06 mg/L (0·03-0·06) in wild-type M tuberculosis., Interpretation: Reduction in the susceptibility of M tuberculosis to bedaquiline has evolved repeatedly across the phylogeny. In our data, we see no evidence that this reduction has led to the spread of a successful strain in South Africa. Binary phenotyping based on the bedaquiline breakpoint might be inappropriate to monitor resistance to this drug. We recommend the use of minimum inhibitory concentrations in addition to MmpR5 truncation screening to identify moderate increases in resistance to bedaquiline., Funding: US Centers for Disease Control and Prevention., Competing Interests: Declaration of interests LWR reports funding from European Molecular Biology Laboratory’s European Bioinformatics Institute (EMBL-EBI). MRF reports grants from NIH/NIAID (5R01AI155765). All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)