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SHINE (Shorter Treatment for Minimal Tuberculosis in Children) was the first Phase 3 paediatric TB treatment-shortening trial. Robust chest X-ray (CXR) classification methods were integral to excluding severe disease for trial eligibility and to retrospectively adjudicating TB status at baseline. We describe and critically evaluate the CXR classification approaches and processes used in the SHINE trial.Children with non-severe TB were randomised to 4- vs 6-months anti-TB treatment. Radiologically non-severe TB was defined on CXR. CXRs were systematically interpreted by on-site clinicians prospectively for eligibility determination and retrospectively by experts to inform adjudication of baseline TB status and disease severity.A screening CXR was successfully obtained from all 1,204 enrolled children; 1,134 CXRs from children with intra-thoracic TB were reviewed by expert readers. Compared with the expert panel, enrolling clinicians classified more CXRs as abnormal and 'typical TB' and all as radiologically non-severe. The expert panel retrospectively classified 71/1,134 (6%) CXRs as severe. Of these, 4 (5.6%) had unfavourable outcomes compared with 34 (3.0%) in the trial overall.Using CXRs to classify radiological disease severity and inform eligibility decisions in real-time by local enrolling clinicians was feasible and safe in this large paediatric TB trial. Retrospective central expert CXR review was successful. Refinement of the CXR methods for the classification of both disease severity and TB status could support standardised implementation in routine care and research..

Limited data exist on mortality rates after tuberculosis (TB) treatment in the United States. We analyzed mortality rates for all adults in Georgia, USA, who had a TB diagnosis and finished treatment during January 1, 2008-December 31, 2019. We obtained posttreatment mortality rate data from the National Death Index and calculated standardized mortality ratios (SMRs) for TB treatment survivors and the general Georgia population. Among 3,182 TB treatment survivors, 233 (7.3%) had died as of December 31, 2019. The overall TB cohort age- and sex-adjusted SMR was 0.89 (95% CI 0.73-1.05). The SMR among US-born TB treatment survivors was 1.56 (95% CI 1.36-1.77). In the TB cohort, US-born status, HIV co-infection, excess alcohol use, diabetes mellitus, and end-stage renal disease were associated with increased risk for death after TB treatment. TB treatment survivors could benefit from improved linkage to primary and HIV comprehensive care to prevent posttreatment death.

Objectives: Although a "multisite" definition of disseminated tuberculosis (DTB) exists, there is limited evidence to support its use. Herein, we sought to generate that evidence., Methods: We evaluated treatment outcomes and reporting requirements against two distinct definitions of DTB in a 15-year population-based cohort of consecutively diagnosed patients with tuberculosis (TB) in Canada. Definitions were combined in a multi-variable logistic regression to determine the risk factors for TB-related death in DTB., Results: We applied two mutually exclusive definitions of DTB to our data set: 1. "strict" - TB disease associated with a positive TB culture in blood/bone marrow or TB disease associated with a miliary pattern on chest imaging and a positive TB culture or, 2. multisite - TB disease in two or more non-contiguous sites. Among 2877 notified patients with TB, 110 (3.8%) met the strict definition, whereas 168 (5.8%) met the multisite definition. Of all 278 patients with DTB, only 135 (48.6%) were notified as DTB using International Classification of Disease codes and only 66 (23.7%) were classified as DTB by Canada's Public Health Agency. Patients with DTB by either definition were less likely to achieve cure/treatment completion and more likely to die. The risk factors for a fatal outcome included extremes of age, Canadian birth, central nervous system involvement, and HIV co-infection., Conclusion: Our findings support the combination of a strict and multisite definition of DTB for purposes of reporting consistency and investigational comparability., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Efforts to shorten rifampicin-resistant tuberculosis (RR-TB) treatment have led to concerns about hepatotoxicity in shorter regimens. We evaluated hepatotoxicity in two novel regimens against the standard shorter regimen recommended by the World Health Organization (WHO)., Methods: Participants from the TB-TRUST and TB-TRUST plus trials were assigned to the WHO shorter regimen, a levofloxacin (Lfx)-based regimen, or a bedaquiline (Bdq)-based regimen. Liver function was tested bi-weekly in the first month, then monthly until treatment ended. Eligibility required receiving at least one drug dose and undergoing at least two liver function tests., Results: Of 429 patients, hepatotoxicity was most prevalent in the WHO shorter group (26.7% of 169), compared to 4.7% in the Lfx group (172 patients), and 5.7% in the Bdq group (88 patients). The median peak alanine aminotransferase levels were 1.67 × upper limit of normal (ULN) for WHO, 0.82 × ULN for Lfx, and 0.88 × ULN for Bdq groups. The incidence of drug-induced liver injury was significantly higher in the WHO group (18.3%) than in the Lfx (3.5%) and Bdq (4.6%) groups. The time to significant alanine aminotransferase elevation was about 2.8 months, with no differences between groups., Conclusions: Two novel regimens demonstrated lower hepatotoxicity compared to the WHO's shorter regimen. Entire course management monitoring is recommended in RR-TB treatment., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Therapeutic drug monitoring (TDM) is a standard clinical procedure that uses the pharmacokinetic and pharmacodynamic parameters of the drug in the body to determine the optimal dose. The pharmacokinetic variability of the drug(s) is a significant contributor to poor treatment outcomes, including the development of acquired drug resistance. TDM aids in dose optimization and improves outcomes while lessening drug toxicity. TDM is used to manage patients with tuberculosis (TB) who exhibit a slow response to therapy, despite good compliance and drug-susceptible organisms. Additional indications include patients at risk of malabsorption or delayed absorption of TB drugs and patients with drug-drug interaction and drug toxicity, which confirm compliance with therapy. TDM usually requires two blood samples: the 2 h and the 6 h post-dose. This narrative review will discuss the pharmacokinetics and pharmacodynamics of TB drugs, determinants of poor response to therapy, indications of TDM, methods of performing TDM, and its interpretations., Methods: This is a narrative review. We searched PubMed, Embase, and the CINAHL from inception to April 2024. We used the following search terms: tuberculosis, therapeutic drug monitoring, anti-TB drugs, pharmacokinetics, pharmacodynamics, limited sample strategies, diabetes and TB, HIV and TB, and multidrug-resistant TB. All types of articles were selected., Results: TDM is beneficial in managing TB, especially in patients with slow responses, drug-resistance TB, recurrent TB, and comorbidities such as diabetes mellitus and human immunodeficiency virus infection., Conclusion: TDM is beneficial for improving outcomes, reducing the risk of acquired drug resistance, and avoiding side effects., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Tuberculosis (T.B.) remains a prominent global cause of health challenges and death, exacerbated by drug-resistant strains such as multidrug-resistant tuberculosis MDR-TB and extensively drug-resistant tuberculosis XDR-TB. For an effective disease management strategy, it is crucial to understand the dynamics of T.B. infection and the impacts of treatment. In the present article, we employ AI-based machine learning techniques to investigate the immunity impact of medications. SEIPR epidemiological model is incorporated with MDR-TB for compartments susceptible to disease, exposed to risk, infected ones, preventive or resistant to initial treatment, and recovered or healed population. These masses' natural trends, effects, and interactions are formulated and described in the present study. Computations and stability analysis are conducted upon endemic and disease-free equilibria in the present model for their global scenario. Both numerical and AI-based nonlinear autoregressive exogenous NARX analyses are presented with incorporating immediate treatment and delay in treatment. This study shows that the active patients and MDR-TB, both strains, exist because of the absence of permanent immunity to T.B. Furthermore, patients who have recovered from tuberculosis may become susceptible again by losing their immunity and contributing to transmission again. This article aims to identify patterns and predictors of treatment success. The findings from this research can contribute to developing more effective tuberculosis interventions., Competing Interests: Declaration of competing interest I have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The disability-adjusted life year (DALY), a key metric for health resource allocation, encompasses morbidity through disability weights. Widely used in tuberculosis cost-effectiveness analysis (CEAs), DALYs play a significant role in informing intervention adopt/reject decisions. This study reviews the values and consistency of disability weights applied in tuberculosis-related CEAs., Methods: We conducted a systematic review using the Tufts CEA database, updated to July 2023 with searches in Embase, Scopus and PubMed. Eligible studies needed to have included a cost-per-DALY ratio, and additionally either evaluated a tuberculosis (TB) intervention or included tuberculosis-related weights. We considered all tuberculosis health states: with/without human immunodeficiency virus (HIV) coinfection, TB treatments and treatment side effects. Data were screened and extracted independently by combinations of two authors., Findings: A total of 105 studies spanning 2002-2023 across 50 countries (mainly low- and middle-income countries) were extracted. Disability weights were sourced primarily from the Global Burden of Disease (GBD; 100/165; 61%), with 17 non-GBD studies additionally referenced, along with primary derivation. Inconsistencies in the utilisation of weights were evident: of the 100 usages of GBD-sourced weights, only in 47 instances (47%) had the weight value been explicitly specified with an appropriate up-to-date reference cited (constituting 28% of all weight usages, 47/165). Sensitivity analyses on weight values had been conducted in 30% of studies (31/105). Twelve studies did not clearly specify weights or their sources; nine further calculated DALYs without morbidity. The review suggests methodological gaps in current approaches for representing important aspects of TB, including TB-HIV coinfection, treatment, drug-resistance, extrapulmonary TB and psychological impacts. We propose a set of best practice recommendations., Interpretation: There is a need for increased rigour in the application, sensitivity testing and reporting of TB disability weights. Furthermore, there appears a desire among researchers to reflect elements of the tuberculosis experience beyond those allowed for by GBD disability weights., (© 2024. The Author(s).)

Objectives: The weekly rifapentine plus isoniazid for 3 months (3HP) improves completion rate of latent tuberculosis infection treatment, but flu-like symptoms are common. The novel 1HP regimen, involving daily rifapentine plus isoniazid for 28 days, has demonstrated low toxicity in HIV-infected populations. We aimed to investigate whether 1HP has a lower incidence rate of systemic drug reaction (SDR) compared with 3HP during treatment in non-HIV populations., Methods: This randomized, multicentre trial compared the completion rate and risks of SDRs of 1HP and 3HP in aged ≥13 years non-HIV subjects with latent tuberculosis infection between September 2019 and September 2023 (ClinicalTrials.gov: NCT04094012). We also investigated associations between SDRs and plasma levels of drugs and their metabolites., Results: A total of 251 and 239 individuals were randomly assigned to 1HP and 3HP groups, respectively, with completion rates of 82.9% (208/251) and 84.5% (202/239), respectively. Among them, 12.7% (32/251) and 10.9% (26/239) of 1HP and 3HP groups experienced SDRs, respectively (p 0.522), predominantly urticaria in 1HP group (59.4% [19/32]) and flu-like syndrome in 3HP group (80.8% [21/26]). Among participants experiencing SDRs, 43.8% (14/32) and 34.6% (9/26) in 1HP and 3HP groups, respectively, completed treatment (p 0.470). Cutaneous reactions were more common in 1HP than 3HP group (32.7% [82/251] vs. 13.0% [31/239], p < 0.001). In 1HP group, urticaria was associated with a higher plasma desacetyl-rifapentine level (ug/mL) at both 2 (median [interquartile range]: 36.06 [17.46-50.79] vs. 22.94 [14.67-31.65], p 0.018) and 6 hours (26.13 [15.80-53.06] vs. 29.83 [18.13-34.01], p 0.047) after dosing., Discussion: In non-HIV population, the incidence rate of SDR under 1HP is not lower than 3HP. Notably, urticaria, rather than flu-like syndrome, was the predominant SDR associated 1HP. The findings of this study underscore the feasibility of 1HP regimen in non-HIV populations with a high-completion rate exceeding 80%., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The study aimed to analyze the clinical effect of MRZE chemotherapy combined with cluster nursing intervention and treatment of pulmonary tuberculosis patients and its influence on CT signs. A total of 94 patients treated in our hospital from March 2020 to October 2021 were selected as the research object. Both groups were treated with MRZE chemotherapy regimen. Patients in the control group received routine nursing mode on this basis, and patients in the observation group received cluster nursing on the basis of the control group. The clinical efficacy, adverse reactions, compliance and nursing satisfaction, detection rate of immune function pulmonary oxygen index and pulmonary function CT signs and the level of inflammatory factors before and after nursing were compared between the two groups. The total effective rate of the observation group was significantly higher than that of the control group. The compliance rate and nursing satisfaction of the observation group were significantly higher than those of the control group. The differences of adverse reactions between the observation and control groups were statistically significant. After nursing, the scores of tuberculosis prevention and control of tuberculosis infection route, tuberculosis symptoms, tuberculosis policy and tuberculosis infection awareness in the observation group were significantly higher than those in the control group, and the differences were statistically significant. MRZE chemotherapy combined with cluster nursing intervention model for pulmonary tuberculosis patients can effectively improve the treatment compliance and nursing satisfaction of patients, and it is worthy of clinical promotion and application.

The Phase 3 randomized controlled trial, TBTC Study 31/ACTG A5349 (NCT02410772) demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pulmonary tuberculosis was safe and effective. The primary efficacy outcome was 12-month tuberculosis disease free survival, while the primary safety outcome was the proportion of grade 3 or higher adverse events during the treatment period. We conducted an analysis of demographic, clinical, microbiologic, radiographic, and pharmacokinetic data and identified risk factors for unfavorable outcomes and adverse events. Among participants receiving the rifapentine-moxifloxacin regimen, low rifapentine exposure is the strongest driver of tuberculosis-related unfavorable outcomes (HR 0.65 for every 100 µg∙h/mL increase, 95%CI 0.54-0.77). The only other risk factors identified are markers of higher baseline disease severity, namely Xpert MTB/RIF cycle threshold and extent of disease on baseline chest radiography (Xpert: HR 1.43 for every 3-cycle-threshold decrease, 95%CI 1.07-1.91; extensive disease: HR 2.02, 95%CI 1.07-3.82). From these risk factors, we developed a simple risk stratification to classify disease phenotypes as easier-, moderately-harder, or harder-to-treat TB. Notably, high rifapentine exposures are not associated with any predefined adverse safety outcomes. Our results suggest that the easier-to-treat subgroup may be eligible for further treatment shortening while the harder-to-treat subgroup may need higher doses or longer treatment., (© 2024. The Author(s).)

Background: Digital adherence technologies (DATs) may provide a patient-centred approach to supporting tuberculosis (TB) medication adherence and improving treatment outcomes. We synthesised evidence addressing costs and cost-effectiveness of DATs to support TB treatment., Methods: A systematic review (PROSPERO-CRD42022313531) identified relevant literature from January 2000 to April 2023 in MEDLINE, Embase, CENTRAL, CINAHL, Web of Science along with preprints from medRxiv, Europe PMC and ClinicalTrials.gov. Studies with observational, experimental or quasi-experimental designs (minimum 20 participants) and modelling studies reporting quantitative data on the cost or cost-effectiveness of DATs for TB infection or disease treatment were included. Study characteristics, cost and cost-effectiveness outcomes were extracted., Results: Of 3619 titles identified by our systematic search, 29 studies met inclusion criteria, of which 9 addressed cost-effectiveness. DATs included short message service (SMS) reminders, phone-based technologies, digital pillboxes, ingestible sensors and video-observed therapy (VOT). VOT was the most extensively studied (16 studies) and was generally cost saving when compared with healthcare provider directly observed therapy (DOT), particularly when costs to patients were included-though findings were largely from high-income countries. Cost-effectiveness findings were highly variable, ranging from no clinical effect in one study (SMS), to greater effectiveness with concurrent cost savings (VOT) in others. Only eight studies adequately reported at least 80% of the elements required by Consolidated Health Economic Evaluation Reporting Standards, a standard reporting checklist for health economic evaluations., Conclusion: DATs may be cost saving or cost-effective compared with healthcare provider DOT, particularly in high-income settings. However, more data of higher quality are needed, notably in lower-income and middle-income countries which have the greatest TB burden., Competing Interests: Competing interests: KS reports research funding from the Canadian Institutes of Health Research. He has also served as chair of the Data Safety and Monitoring Board for a COVID-19 therapeutic investigated by Laurent Pharmaceuticals., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

This study aims to explore the clinical efficacy and feasibility of preoperative 1-week chemotherapy for patients with spinal tuberculosis (STB) undergoing complete lesion removal. Clinical data of 76 patients with STB who underwent complete focal debridement in our hospital were collected from June 2020 to September 2023. The patients were divided into 38 cases of preoperative 1-week chemotherapy group (Group A) according to the length of preoperative chemotherapy, and 38 cases of preoperative 2 to 4-week chemotherapy group (Group B). Perioperative related, imaging, and laboratory examination indices as well as postoperative neurological function recovery, postoperative pain recovery, related complications, and clinical efficacy were analyzed to compare the clinical efficacy of the 2 groups. All patients successfully completed the treatment of stage I complete lesion removal combined with bone grafting fusion and internal fixation. The difference in erythrocyte setting rate and C-reactive protein at the same postoperative observation time between the 2 groups was not statistically significant (P > .05). The visual analogue scale scores of patients in the 2 groups decreased significantly with prolonged time, and the difference was statistically significant (P < .05). All patients achieved satisfactory clinical efficacy (P < .05). All patients achieved good clinical outcomes, the difference between the groups was not statistically significant (P > .05). The difference in incision healing rate at 3 months postoperatively and bone graft fusion rate at 6 months postoperatively was not statistically significant between the 2 groups (P > .05). The dissemination and recurrence of Mycobacterium tuberculosis were not statistically significantly different between the 2 groups after surgery (P > .05). In summary, with complete lesion clearance, 1 week of preoperative chemotherapy is feasible in patients with STB with varying degrees of neurological dysfunction., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

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: To analyze the clinical manifestations, diagnostic and therapeutic processes of perinatal tuberculosis in children, providing reference for clinicians in the diagnosis and treatment of this disease., Methods: A retrospective analysis was conducted on the epidemiological history, clinical manifestations, laboratory and imaging findings, and treatment follow-up of 20 cases of perinatal tuberculosis diagnosed in the Second Department of Infectious Disease, Kunming Children's Hospital, from February 2014 to September 2021., Results: Of the 20 cases, 13 were male (65.0%) and 7 were female (35.0%). The average age at onset was 35.35 ± 23.03days, with an average time from onset to diagnosis of 24.75 ± 15.55days. Tuberculin skin test (TST) was positive in 1 out of 4 cases (25.0%). Gamma interferon release assays (IGRAs) were positive in 9 out of 17 cases (52.9%).acid-fast staining was positive in 7 out of 16 cases (43.7%), and Mycobacterium tuberculosis nucleic acid polymerase-chain-reaction(PCR) was positive in 14 out of 20 cases (70.0%). Chest CT showed miliary changes in 4 out of 19 cases (21.0%), multiple nodular and patchy opacities in 6 out of 19 cases (31.6%), and pulmonary consolidation and atelectasis in 10 out of 19 cases (52.6%). After anti-tuberculosis treatment, 16 out of 20 cases (80.0%) improved, and no recurrence of tuberculosis was observed during follow-up periods ranging from 9 months to 3 years. The growth and development of these children were similar to those of healthy children., Conclusion: The clinical manifestations and chest imaging features of perinatal tuberculosis are nonspecific. In suspected cases, it is crucial to investigate the mother's condition thoroughly and complete etiological examinations to achieve early diagnosis and timely treatment, which can improve prognosis., (© 2024. The Author(s).)

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).)

Introduction: Intestinal obstruction is a common complication in patients with advanced malignancies, often attributed to the disease itself or as a side effect of opioid analgesics used for pain management. However, the occurrence of intestinal obstruction following antituberculosis therapy is rare., Case Presentation: We report a unique case of a 58-year-old Asian male diagnosed with stage IV pancreatic carcinoma and pulmonary tuberculosis. The patient was initiated on a regimen of ethambutol hydrochloride, pyrazinamide, rifampicin, and isoniazid tablets (II) for tuberculosis, alongside morphine for the management of severe cancer-related pain. Subsequently, he developed symptoms indicative of intestinal obstruction. Despite discontinuation of morphine, the patient's symptoms persisted until he autonomously ceased all medications, leading to a rapid improvement in his condition. This unexpected resolution highlighted the antituberculosis drugs as the probable cause of his intestinal obstruction., Conclusions: This case underscores the importance of considering antituberculosis drugs as a potential cause of intestinal obstruction, especially in patients who do not respond to conventional management strategies for drug-induced gastrointestinal side effects. It also emphasizes the need for heightened vigilance and monitoring when prescribing these medications to patients with advanced malignancies, to promptly identify and address rare but significant side effects., (© 2024. The Author(s).)

Background: The end tuberculosis (TB) strategy requires a novel patient treatment approach contrary to the one-size-fits-all model. It is well known that each patient's physiology is different and leads to various rates of drug elimination. Therapeutic drug monitoring (TDM) offers a way to manage drug dosage adaptation but requires trained pharmacologists, which is scarce in resource-limited settings., Objective: We will develop an automated clinical decision support system (CDSS) to help practitioners with the dosage adaptation of rifampicin, one of the essential medical drugs targeting TB, that is known for large pharmacokinetic variability and frequent suboptimal blood exposure. Such an advanced system will encourage the spread of a dosage-individualization culture, including among practitioners not specialized in pharmacology. Thus, the objectives of this project are to (1) develop the appropriate population pharmacokinetic (popPK) model for rifampicin for Tanzanian patients, (2) optimize the reporting of relevant information to practitioners for drug dosage adjustment, (3) automate the delivery of the report in line with the measurement of drug concentration, and (4) validate and implement the final system in the field., Methods: A total of 3 teams will combine their efforts to deliver the first automated TDM CDSS for TB. A cross-sectional study will be conducted to define the best way to display information to clinicians. In parallel, a rifampicin popPK model will be developed taking advantage of the published literature, complemented with data provided by existing literature data from the Pan-African Consortium for the Evaluation of Antituberculosis Antibiotics (panACEA), and samples collected within this project. A decision tree will be designed and implemented as a CDSS, and an automated report generation will be developed and validated through selected case studies. Expert pharmacologists will validate the CDSS, and finally, field implementation in Tanzania will occur, coupled with a prospective study to assess clinicians' adherence to the CDSS recommendations., Results: The TuberXpert project started in November 2022. In July 2024, the clinical study in Tanzania was completed with the enrollment of 50 patients to gather the required data to build a popPK model for rifampicin, together with a qualitative study defining the report design, as well as the CDSS general architecture definition., Conclusions: At the end of the TuberXpert project, Tanzania will possess a new tool to help the practitioners with the adaptation of drug dosage targeting complicated TB cases (TB or HIV, TB or diabetes mellitus, and TB or malnutrition). This automated system will be validated and used in the field and will be proposed to other countries affected by endemic TB. In addition, this approach will serve as proof of concept regarding the feasibility and suitability of CDSS-assisted TDM for further anti-TB drugs in TB-burdened areas deprived of TDM experts, including second-line treatments considered important to monitor., International Registered Report Identifier (irrid): DERR1-10.2196/58720., (©Yann Thoma, Annie E Cathignol, Yuan J Pétermann, Margaretha L Sariko, Bibie Said, Chantal Csajka, Monia Guidi, Stellah G Mpagama. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 21.10.2024.)

Background: Drug-resistant (DR) tuberculosis (TB) is typically characterized by resistance to a single or combination of first- and/or second-line anti-TB agents and commonly includes rifampicin-resistant (RR)-TB, multidrug-resistant (MDR)-TB, pre-extensively drug-resistant (pre-XDR)-TB and XDR-TB. Historically, all variations of DR-TB required treatment with second-line drugs which are less effective and more toxic than first-line options, have a longer treatment duration and are more expensive to both patients and providers. The World Health Organization (WHO) now recommends a new second-line 3-drug 6-month all-oral regimen consisting of bedaquiline, pretomanid, and linezolid referred to as BPaL. We estimate patient and provider costs of DR-TB treatment with BPaL compared to the current standard of care in South Africa., Methods and Findings: In coordination with South Africa's BPaL clinical access programme (CAP) we conducted an economic evaluation of A) patient costs through a cross-sectional patient cost survey and B) provider costs through a bottom-up costing analysis consisting of a retrospective medical record review (patient resource-use) and top-down financial record review (fixed/shared costs such as overhead). Across both costing perspectives, we compare costs of 1) BPaL, to current standard of care options including the 2) 9-11-month standard short oral regimen (SSOR) and 3) 18-21-month standard long oral regimen (SLOR). Eligible patients included those ≥14 years old with confirmed sputum pulmonary RR/MDR-TB, pre-XDR or XDR-TB. All costs are reported in 2022 United States Dollar (US$). A total of 72 patients were enrolled and completed the patient cost survey (41.7% on BPaL, 16.7% on the SSOR and 41.7% on the SLOR). Mean on-treatment patient costs were lowest among those on BPaL ($56.6) and increased four-fold among those on the SSOR ($228.1) and SLOR ($224.7). Direct medical patient costs were negligible across all treatment regimens, while direct non-medical patient and guardian costs for travel, food and nutritional supplementation accounted for the largest proportion of total costs ($54.6, $227.8 and $224.3 for BPaL, the SSOR and SLOR respectively). In assessing provider costs, a total of 112 medical records were reviewed (37.5%, 41.1% and 21.4% on BPaL, the SSOR and SLOR respectively). Total provider costs for producing a favorable treatment outcome (cured/completed treatment) were similar among those on BPaL ($4,948.7 per patient) and the SSOR ($4,905.6 per patient) with costs increasing substantially among those on the SLOR ($8,919.9 per patient). Based on incremental cost-effectiveness ratios (ICERs), at even the lowest willingness to pay (WTP) threshold, treatment with the new BPaL regimen was more cost-effective than current standard of care treatment options (ICER: $311.4 < WTP: $3,341)., Conclusions: When using the newly recommended BPaL regimen, cost to patients decreased by 75% compared to current standard of care treatment options in South Africa. Due in part to higher resource-use within the BPaL CAP offsetting the shorter treatment duration, cost of treatment provision through BPaL and the 9-11-month SSOR were similar. However, when considering cost and treatment outcomes, BPaL was more cost-effective than other standard of care regimens currently available for DR-TB in South Africa., Competing Interests: I have read the journal’s policy and the authors of this manuscript have no competing interests., (Copyright: © 2024 Evans 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.)

Loss to follow-up (LTFU) in tuberculosis (TB) management increases morbidity and mortality, challenging effective control strategies. This study aims to develop and evaluate machine learning models to predict loss to follow-up in TB patients, improving treatment adherence and outcomes. Retrospective data encompassing tuberculosis patients who underwent treatment or registration at the National Center for Clinical Medical Research on Infectious Diseases from January 2017 to December 2021 were compiled. Employing machine learning techniques, namely SVM, RF, XGBoost, and logistic regression, the study aimed to prognosticate LTFU. A comprehensive cohort of 24,265 tuberculosis patients underwent scrutiny, revealing a LTFU prevalence of 12.51% (n = 3036). Education level, history of hospitalization, alcohol consumption, outpatient admission, and prior tuberculosis history emerged as precursors for pre-treatment LTFU. Employment status, outpatient admission, presence of chronic hepatitis/cirrhosis, drug adverse reactions, alternative contact availability, and health insurance coverage exerted substantial influence on treatment-phase LTFU. XGBoost consistently surpassed alternative models, boasting superior discriminative ability with an average AUC of 0.921 for pre-treatment LTFU and 0.825 for in-treatment LTFU. Our study demonstrates that the XGBoost model provides superior predictive performance in identifying LTFU risk among tuberculosis patients. The identification of key risk factors highlights the importance of targeted interventions, which could lead to significant improvements in treatment adherence and patient outcomes., (© 2024. The Author(s).)

A paradoxical reaction (PR) during the treatment of tuberculosis was defined as the worsening of preexisting disease either clinically or radiologically or the appearance of a new tuberculous lesion. These reactions are frequently observed in patients coinfected with human immunodeficiency virus (HIV) upon the initiation of antiretroviral therapy (ART). Herein, we present a unique case of a paradoxical reaction in a previously healthy 19-year-old female who started anti-tuberculosis treatment for disseminated tuberculosis. Four weeks after treatment initiation, she developed two new swollen masses in her left dorsum of the hand, accompanied by fever and new right submandibular painful lymphadenopathy, with worsening of the preexisting left lower neck lymph node. The patient underwent needle aspiration from her new skin abscess on the dorsum of her left hand, which revealed positive polymerase chain reaction (PCR) for Mycobacterium tuberculosis. Anti-tuberculosis treatment was continued, and the patient fully recovered. We described an unusual presentation of paradoxical reaction manifested by a skin abscess at a site distant from her primary disease in an immunocompetent TB patient, which demonstrated the importance of considering paradoxical reactions in HIV-negative patients who present with worsening signs and symptoms after initial improvement following treatment initiation., (© 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).)

Despite advancements in detection and treatment, tuberculosis (TB), an infectious illness caused by the Mycobacterium TB bacteria, continues to pose a serious threat to world health. The TB diagnosis phase includes a patient's medical history, physical examination, chest X-rays, and laboratory procedures, such as molecular testing and sputum culture. In artificial intelligence (AI), machine learning (ML) is an advanced study of statistical algorithms that can learn from historical data and generalize the results to unseen data. There are not many studies done on the ML algorithm that enables the prediction of treatment success for patients with pulmonary TB (PTB). The objective of this study is to identify an effective and predictive ML algorithm to evaluate the detection of treatment success in PTB patients and to compare the predictive performance of the ML models. In this retrospective study, a total of 1236 PTB patients who were given treatment under a randomized controlled clinical trial at the ICMR-National Institute for Research in Tuberculosis, Chennai, India were considered for data analysis. The multiple ML models were developed and tested to identify the best algorithm to predict the sputum culture conversion of TB patients during the treatment period. In this study, decision tree (DT), random forest (RF), support vector machine (SVM) and naïve bayes (NB) models were validated with high performance by achieving an area under the curve (AUC) of receiver operating characteristic (ROC) greater than 80%. The salient finding of the study is that the DT model was produced as a better algorithm with the highest accuracy (92.72%), an AUC (0.909), precision (95.90%), recall (95.60%) and F1-score (95.75%) among the ML models. This methodology may be used to study the precise ML model classification for predicting the treatment success of TB patients during the treatment period., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ahamed Fayaz 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.)

A young man in his early 30s presented to our hospital with upper abdominal pain radiating to the back, progressive jaundice with pruritus, low-grade fever, vomiting and significant weight loss over 4 months. The syndrome of extrahepatic biliary obstruction was considered. There was no significant past, personal or family history. Imaging was suggestive of mucinous cystic lesions of the pancreas with significant lymphadenopathy. He was initially planned for surgery. However, endoscopic ultrasound-guided fine-needle aspiration from the lesion tested positive for tuberculosis and he improved dramatically with antituberculosis therapy. When a patient has an atypical presentation, tuberculosis should always be considered, especially if they reside in a tuberculosis-endemic country., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We aimed to evaluate the predictors for early and interim culture conversion within 2 months and 6 months of treatment in multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) patients in China., Methods: This study included adult MDR/RR-TB patients with a positive baseline sputum culture from 8 institutions located in different cities in China from May 2018 to January 2022. We mainly used logistic regression model to derive possible predictors of early and interim culture conversion., Results: A total of 813 patients were enrolled and 28.5% of them received multidrug-resistant treatment regimens containing bedaquiline. Of these, 362 (44.5%) patients experienced culture conversion within 2 months of treatment, and 649 (79.8%) within 6 months. The results of the multivariable logistic regression analysis revealed that acid-fast bacilli smear positive (adjusted odds ratio [aOR] = 1.637, 95% confidence interval [CI] = 1.197-2.238), cavities (aOR = 1.539, 95% CI = 1.132-2.092), bilateral disease (aOR = 1.638, 95% CI = 1.183-2.269), and viral hepatitis (aOR = 2.585, 95% CI = 1.189-5.622) were identified as risk factors for early culture un-conversion within 2 months of treatment. Additionally, smoking history (aOR = 2.197, 95% CI = 1.475-3.273), previous treatment for tuberculosis (aOR = 1.909, 95% CI = 1.282-2.844), bilateral disease (aOR = 2.201, 95% CI = 1.369-3.537), viral hepatitis (aOR = 2.329, 95% CI = 1.094-4.962) were identified as risk factors for interim culture un-conversion within 6 months of treatment, while patients with regimen containing bedaquiline (aOR = 0.310, 95% CI = 0.191-0.502) was a protective factor., Conclusions: A history of smoking, a baseline sputum AFB smear positive, lung cavities, bilateral disease, previous anti-tuberculosis treatment, or a comorbidity of viral hepatitis can be used as the predictors for early and interim culture un-conversion in MDR/RR-TB patients, while bedaquiline was a protective factor ., (© 2024. The Author(s).)

Introduction: Tuberculosis (TB) treatment demands strict adherence to multidrug regimens. Directly Observed Therapy (DOT) poses challenges, especially regarding adherence. With the popularization of smartphones, Video-Observed Therapy (VOT) has emerged as a promising alternative, allowing healthcare providers to remotely supervise patients taking their medications via video calls., Objectives: This systematic review critically assesses VOT's effectiveness compared to DOT, focusing on adherence, treatment costs, time spent supervising treatment, and patient satisfaction, aiming to optimize TB supervision methods worldwide., Methods: Only studies that met the following criteria were eligible for inclusion in the systematic review: randomized trials; studies that compared VOT to DOT; studies involving patients diagnosed with pulmonary or extrapulmonary tuberculosis; studies that reported any of the desired outcomes; full-text articles available for review; and studies conducted in the English language. We excluded studies with the following attributes: studies that lacked a control group; case series or case reports; and previous systematic reviews. The search engines and databases MEDLINE, Embase, and Cochrane were used to find studies comparing Video-Observed Therapy (VOT) to Directly Observed Therapy (DOT). The following search phrases were used to look for papers that contained them in their title or abstract: ("Electronic Directly Observed Therapy" OR "Video-observed therapy" OR "Telemedicine" OR "Wirelessly observed therapy" OR "Smartphone-enabled video-observed") AND ("TUBERCULOSIS")., Results: A systematic review of the literature revealed the following findings: in all Randomized Controlled Trials (RCTs), video-observed therapy (VOT) demonstrated non-inferiority in terms of treatment adherence compared to traditional directly observed therapy (DOT); VOT reduced costs where these outcomes were assessed in the RCTs; the use of VOT reduced the amount of time healthcare professionals spent supervising treatment in RCTs evaluating this aspect; VOT contributed to higher treatment satisfaction in RCTs where this outcome was measured., Conclusion: In this systematic review we emphasize the importance of Video-Observed Therapy (VOT) in the digital age for patients that have access to internet. Our findings show that VOT is comparable to DOT in terms of treatment adherence, but it is also cost-effective, improves patient satisfaction and takes less time for healthcare professionals to supervise., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Areas Lisboa Netto 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.)

Background: One month of daily rifapentine + isoniazid (1HP) is an effective, ultrashort option for tuberculosis prevention in people with human immunodeficiency virus (HIV). However, rifapentine may decrease antiretroviral drug concentrations and increase the risk of virologic failure. AIDS Clinical Trials Group A5372 evaluated the effect of 1HP on the pharmacokinetics of twice-daily dolutegravir., Methods: A5372 was a multicenter, pharmacokinetic study in people with HIV (≥18 years) already on dolutegravir-containing antiretroviral therapy with HIV RNA <50 copies/mL. Participants received daily rifapentine/isoniazid (600 mg/300 mg) for 28 days as part of 1HP. Dolutegravir was increased to 50 mg twice daily during 1HP, and intensive pharmacokinetic sampling was performed on day 0 (before 1HP) and on the final day of 1HP treatment., Results: Thirty-two participants (41% female; 66% Black/African; median [Q1, Q3] age, 42 [34, 49] years) were included in the pharmacokinetic analysis; 31 had HIV RNA <50 copies/mL at the end of 1HP dosing. One participant had an HIV RNA of 160 copies/mL at day 28, with HIV RNA <50 copies/mL upon repeat testing on day 42. The median (Q1, Q3) dolutegravir trough concentration was 1751 ng/mL (1195, 2542) on day 0 versus 1987 ng/mL (1331, 2278) on day 28 (day 28:day 0 geometric mean ratio, 1.05 [90% confidence interval, .93-1.2]; P = .43). No serious adverse events were reported., Conclusions: Dolutegravir trough concentrations with 50 mg twice-daily dosing during 1HP treatment were greater than those with standard-dose dolutegravir once daily without 1HP. These pharmacokinetic, virologic, and safety data provide support for twice-daily dolutegravir use in combination with 1HP for tuberculosis prevention., Clinical Trials Registration: NCT04272242., Competing Interests: Potential conflicts of interest. A.F.L. has contracts for clinical research unrelated to this work from Gilead, ViiV, and Merck; consulting fees from ViiV. A.A. reports grants from Gilead, ViiV, Roche, GSK and MSD unrelated to this work. S.S. reports grants from ViiV unrelated to the present work. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: In 2019, the World Health Organization called for operational research on all-oral shortened regimens for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB). We report safety and effectiveness of three 9-month all-oral regimens containing bedaquiline (Bdq), linezolid (Lzd), and levofloxacin (Lfx) and reinforced with cycloserine (Cs) and clofazimine (Cfz), delamanid (Dlm) and pyrazinamide (Z), or Dlm and Cfz., Methods: We conducted a prospective cohort study of patients initiating treatment for pulmonary MDR/RR-TB under operational research conditions at public health facilities in Kazakhstan. Participants were screened monthly for adverse events. Participants with baseline resistance were excluded from the study and treated with a longer regimen. We analyzed clinically relevant adverse events of special interest in all participants and sputum culture conversion and end-of-treatment outcomes among individuals who were not excluded., Results: Of 510 participants, 41% were women, the median age was 37 years (25th-75th percentile: 28-49), 18% had a body mass index <18.5 kg/m2, and 51% had cavitary disease. A total of 399 (78%) initiated Bdq-Lzd-Lfx-Cs-Cfz, 83 (16%) started Bdq-Lzd-Lfx-Dlm-Z, and 28 (5%) initiated Bdq-Lzd-Lfx-Dlm-Cfz. Fifty-eight individuals (11%) were excluded from the study, most commonly due to identification of baseline drug resistance (n = 52; 90%). Among the remaining 452 participants, treatment success frequencies were 92% (95% CI: 89-95%), 89% (95% CI: 80-94%), and 100% (95% CI: 86-100%) for regimens with Cs/Cfz, Dlm/Z, and Dlm/Cfz, respectively. Clinically relevant adverse events of special interest were uncommon., Conclusions: All regimens demonstrated excellent safety and effectiveness, expanding the potential treatment options for patients, providers, and programs., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

In this prospective cohort of 2006 individuals with drug-susceptible tuberculosis in India, 18% had unfavorable treatment outcomes (4.7% treatment failure, 2.5% recurrent infection, 4.1% death, 6.8% loss to follow-up) over a median 12-month follow-up period. Age, male sex, low education, nutritional status, and alcohol use were predictors of unfavorable outcomes., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Tuberculous meningitis (TBM) with adults Epstein-Barr (EB) virus encephalitis is a very rare infectious disease, with a high mortality and disability. Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) is highly diagnostic. We report on a case of severe meningoencephalitis caused by co-infection with mycobacterium tuberculosis and EB virus. Brain MRI indicated a parenchyma lesion in the brain. mNGS of CSF indicated Mycobacterium tuberculosis and EB virus amplification, positive serum EB virus IgG antibodies, and improved symptoms after anti-tuberculosis and antiviral treatment. A re-examination of the brain MRI revealed that the significantly absorption of the lesions., Case Report: A 49-year-old male patient presented with a chief complaint of headache and fever with consciousness disturbance. The brain magnetic resonance imaging showed a lesions in the right parenchymal brain with uneven enhancement, accompanied by significantly increased intracranial pressure, elevated CSF cell count and protein levels, as well as notably decreased glucose and chloride levels. mNGS of CSF showed the coexistence of Mycobacterium tuberculosis and EBV. The patient was diagnosed as TBM with EBV encephalitis. The patient's symptoms gradually improved with the active administration of anti-tuberculosis combined with antiviral agents, the use of hormones to reduce inflammatory reaction, dehydration to lower intracranial pressure, and intrathecal injection. Subsequent follow-up brain magnetic resonance imaging indicated significant absorption of the lesions, along with a marked decrease in CSF count and protein levels, as well as obvious increase in glucose and chloride levels., Conclusion: TBM associated with adult EBV encephalitis is extremely rare. The disease's early stages are severe and have a high fatality rate. A prompt and accurate diagnosis is particularly important. NGS of CSF is of great value for early diagnosis., Competing Interests: The author declares 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 Wang, Li, Zhu, Cheng and Kong.)

Background: The COVID-19 pandemic negatively impacted tuberculosis (TB) treatment services, including directly observed therapy (DOT) programs used to promote medication adherence. We compared DOT adherence embedded in a research study before and after COVID-19 lockdowns in South Africa., Methods: We analyzed data from 263 observational study participants undergoing drug susceptible (DS)-TB DOT between May 2017 to March 2022. Participants enrolled before October 2019 were considered 'pre-COVID-19' and those enrolled after September 2020 were considered 'post-COVID-19 lockdown groups. Negative binomial regression models were used to compare DOT non-adherence rates between the two lockdown groups. We then conducted a sensitivity analysis which only included participants enrolled in the immediate period following the first COVID-19 lockdown., Results: DOT non-adherence rate was higher in the post-COVID-19 lockdown group (aIRR = 1.42, 95% CI = 1.04-1.96; p = 0.028) compared to pre-COVID-19 lockdown period, adjusting for age, sex, employment status, household hunger, depression risk, and smoked substance use. DOT non-adherence was highest immediately following the initial lockdown (aIRR = 1.74, 95% CI = 1.17-2.67; p = 0.006)., Conclusion: The COVID-19 lockdowns adversely effected adherence to TB DOT in the period after lockdowns were lifted. The change in DOT adherence persisted even after adjusting for socioeconomic and behavioral variables. We need a better understanding of what treatment adherence barriers were exacerbated by COVID-19 lockdowns to improve outcomes in post-pandemic times., Trial Registration: ClinicalTrials.gov Registration Number: NCT02840877. Registered on 19 July 2016., (© 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).)

Tuberculosis (TB) is a global public health concern and a leading cause of death. Its persistence occurs mainly because barriers in the care cascade are not being fully addressed. Healthcare professionals and scientists have been addressing treatment challenges such as abandonment and irregular drug intake via strategies such as directly observing treatment and singular therapeutic projects to improve adherence. However, while protocols and guidelines advocate these strategies, their implementation requires a broader approach from healthcare teams. This article examines the importance of such strategies in clinical TB management and analyzes an unfavorable outcome in an immunocompetent patient treated for pulmonary tuberculosis (PTB) from 2017 to 2022. After recurrence and treatment, the patient continued to have persistent acid-fast bacilli in the sputum, positive cultures for Mycobacterium tuberculosis, and progressive lung lesions, despite receiving the recommended treatment. Although categorized as having an intermediate risk of treatment abandonment, the patient faced challenges, such as the COVID-19 pandemic, pregnancy, and being diagnosed with COVID-19. After therapeutic failure and the loss of beneficial prospects, palliative care was initiated. This case illustrates the complexities of managing TB in patients with recurrent disease despite apparent adherence to treatment. After reassessing the risk of abandonment score, the patient was categorized as high-risk. This underscores the importance of singular therapeutic projects, such as psychological support for high-risk or intermediate patients, to prevent negative outcomes. This case reinforces the critical need for comprehensive patient-centered approaches to successfully treat and manage TB.

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).)

Tuberculosis (TB) is a serious infection that can involve any organ system and present in various forms. About one-third of the world's population are carriers of latent TB. Although most cases are from a pulmonary origin, there is a rising prevalence of abdominal TB. Patients with pulmonary or extrapulmonary TB are treated similarly through the use of pharmacological therapy. Nonspecific clinical manifestations of TB have made it difficult for clinicians to diagnose. Peritoneal tuberculosis (PTB) is a serious concern as its symptoms overlap with that of many other chronic conditions, especially in those who are immunocompromised. The lack of highly sensitive and specific testing methods has made early intervention difficult, therefore a high index of suspicion is crucial in the progression of the disease. Here, we present a case of a 71-year-old female with a history of abdominal pain, fever, and weakness. Initial investigation with computed tomography (CT) imaging revealed omental fat stranding that pointed towards peritoneal carcinomatosis (PC) from possible recurrence of her ovarian cancer. Further investigation with a peritoneal biopsy was remarkable for caseating granulomas with fat necrosis confirming extrapulmonary TB. This report highlights a rare case of PTB mimicking PC in an elderly patient who is immunocompromised from the use of long-term corticosteroids who continued to decline after pharmacological treatment of the disease., (© 2024. The Author(s).)

Tuberculosis (TB), induced by Mycobacterium tuberculosis (Mtb) infection, remains a major public health issue worldwide. Mtb has developed complicated strategies to inhibit the immunological clearance of host cells, which significantly promote TB epidemic and weaken the anti-TB treatments. Host-directed therapy (HDT) is a novel approach in the field of anti-infection for overcoming antimicrobial resistance by enhancing the antimicrobial activities of phagocytes through phagosomal maturation, autophagy and antimicrobial peptides. Autophagy, a highly conserved cellular event within eukaryotic cells that is effective against a variety of bacterial infections, has been shown to play a protective role in host defense against Mtb. In recent decades, the introduction of nanomaterials into medical fields open up a new scene for novel therapeutics with enhanced efficiency and safety against different diseases. The active modification of nanomaterials not only allows their attractive targeting effects against the host cells, but also introduce the potential to regulate the host anti-TB immunological mechanisms, such as apoptosis, autophagy or macrophage polarization. In this review, we introduced the mechanisms of host cell autophagy for intracellular Mtb clearance, and how functional nanomaterials regulate autophagy for disease treatment. Moreover, we summarized the recent advances of nanomaterials for autophagy regulations as novel HDT strategies for anti-TB treatment, which may benefit the development of more effective anti-TB treatments., (© 2024. The Author(s).)

Despite known treatments, tuberculosis (TB) remains the world's top infectious killer, highlighting the pressing need for new drug regimens. To prioritize the most efficacious drugs for clinical testing, we previously developed a PK-PD translational platform with bacterial dynamics that reliably predicted short-term monotherapy outcomes in Phase IIa trials from preclinical mouse studies. In this study, we extended our platform to include PK-PD models that account for drug-drug interactions in combination regimens and bacterial regrowth in our bacterial dynamics model to predict cure at the end of treatment and relapse 6 months post-treatment. The Phase III STAND trial testing a new regimen comprised of pretomanid (Pa), moxifloxacin (M), and pyrazinamide (Z) (PaMZ) was suspended after a separate ongoing trial (NC-005) suggested that adding bedaquiline (B) to the PaMZ regimen would improve efficacy. To forecast if the addition of B would, indeed, benefit the PaMZ regimen, we applied an extended translational platform to both regimens. We predicted currently available short- and long-term clinical data well for drug combinations related to BPaMZ. We predicted the addition of B to PaMZ to shorten treatment duration by 2 months and to have similar bacteriological success to standard HRZE treatment (considering only treatment success but not withdrawal from side effects and other adverse events), both at the end of treatment for treatment efficacy and 6 months after treatment has ended in relapse prevention. Using BPaMZ as a case study, we have demonstrated our translational platform can predict Phase II and III outcomes prior to actual trials, allowing us to better prioritize the regimens most likely to succeed., Competing Interests: The authors declare no conflict of interest.

Background: The reactivation of tuberculosis (TB) among kidney transplant (KT) recipients in an endemic area is of general concern. However, the epidemiology of latent TB infection (LTBI) status and its dynamic change responses have not been explored., Methods: Between September 2020 and August 2021, a prospective study was conducted to investigate the status of LTBI in KT recipients who received a 9-month isoniazid universal prophylaxis. This status was measured using the interferon-gamma release assay (IGRA) with T-SPOT.TB before transplant, as well as at one month and nine months post-transplant., Results: Ninety-one KT recipients had a mean (SD) age of 45 (11) years, and 41% were female. Sixty-eight (75%) patients received a deceased donor allograft, and eighty-six (91%) patients received induction immunosuppressive therapy. The IGRA results were positive, borderline, negative, and indeterminate in 14 (15.4%), 6 (6.6%), 64 (70.3%), and 7 (7.8%) patients, respectively. Among 84 evaluable patients, 20 (23.8%) KT recipients were defined as having LTBI. Older age was significantly associated with LTBI (OR 1.06 [95% CI 1.01-1.12], p = 0.03). Among the 77 KT recipients who completed monitoring, 55 had negative IGRA results. Three (5.4%) KT recipients had conversion post-transplant. One of them developed pulmonary TB at 1 week after the transplant. Among the 13 patients with positive results, 8 (61.5%) remained positive, 1 (7.7%) had an indeterminate result at 1-month post-transplant and subsequently tested positive at 9 months post-transplant, and 4 (30.8%) experienced reversion to negative results throughout the study., Conclusions: In a high TB-endemic area, one-quarter of KT recipients were reported to have LTBI, and the dynamic change of IGRA response in KT recipients is plausible post-transplant., (© 2024. The Author(s).)

Background: Drug resistance (DR) is one of the several challenges to global tuberculosis (TB) control. The implementation of bedaquiline (BED) for DR-TB after more than 40 years was expected to improve treatment outcomes as well as microbiologic conversion and adverse events (AE) occurrence., Methods: Retrospective cohort study based on secondary data of patients with rifampicin-resistant (RR) or multidrug-resistant (MDR) TB reported to the Outpatient Clinic of Mycobacterial Diseases of the Thorax Diseases Institute - Federal University of Rio de Janeiro - Brazil, between 2016 and 2023. We aimed to evaluate microbiologic conversion, AE and TB treatment outcomes and compare them according to the treatment regimen used for RR/MDR-TB patients under routine conditions [Injectable Containing Regimens (ICR) versus BED Containing Regimens (BCR)]. Logistic regression and survival analysis using Cox regression and Kaplan Meier curve were used for statistical analysis., Results: Of the 463 DR-TB patients notified during the study period, 297 (64.1%) were included for analysis (ICR = 197 and BCR = 100). Overall AEs were more frequent (83.7 vs. 16.3%, p < 0.001) and occurred earlier in the ICR group (15 days vs. 65 days, p = 0.003). There were no cases of cardiotoxicity requiring interruption of BED treatment. None of the regimens of treatment tested were associated with smear or culture conversion on Cox regression analysis (p = 0.60 and 0.88, respectively). BED-containing regimens were also associated with favorable outcomes in multivariable logistic regression [adjusted odds ratio (aOR) = 2.63, 95% confidence interval (CI)1.36-5.07, p = 0.004], as higher years of schooling, primary drug resistance, and no previous TB treatment. In the survival analysis, BCR was inversely associated with the occurrence of AE during treatment follow-up (aHR 0.24, 95% CI 0.14-0.41, p < 0.001). In addition, TB treatment regimens with BED were also associated with favorable outcomes (aHR 2.41, 95% CI 1.62-3.57, p < 0.001), along with no illicit drug use and primary drug resistance., Conclusions: The implementation of a fully oral treatment for RR/MDR-TB in a reference center in Brazil was safe and associated with favorable outcomes under routine conditions, despite social, demographic, and behavioral factors that may influence TB treatment completion., (© 2024. The Author(s).)

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb) infection, remains a deadly global public health burden. The use of recommended drug combinations in clinic has seen an increasing prevalence of drug-resistant TB, adding to the impediments to global control of TB. Therefore, control of TB and drug-resistant TB has become one of the most pressing issues in global public health, which urges the exploration of potential therapeutic targets in TB and drug-resistant TB. Pyroptosis, a form of programmed cell death characterized by cell swelling and rupture, release of cellular contents and inflammatory responses, has been found to promote pathogen clearance and adopt crucial roles in the control of bacterial infections. It has been demonstrated that Mtb can cause host cell pyroptosis, and these host cells, which are infected by Mtb, can kill Mtb accompanied by pyroptosis, while, at the same time, pyroptosis can also release intracellular Mtb, which may potentially worsen the infection by exacerbating the inflammation. Here, we describe the main pathways of pyroptosis during Mtb infection and summarize the identified effectors of Mtb that regulate pyroptosis to achieve immune evasion. Moreover, we also discuss the potentials of pyroptosis to serve as an anti-TB therapeutic target, with the aim of providing new ideas for the development of TB treatments.

Background: Ethiopia faces a significant burden of Tuberculosis (TB), being one of the high-burden countries, and the emergence of the Coronavirus Disease 2019 (COVID-19) has become a dominant health concern, particularly in resource-limited settings. The repercussions of COVID-19 on TB care are evident, leading to a surge in undiagnosed TB cases, challenges in medication adherence, and an escalation of drug resistance. Consequently, a thorough assessment of the impact of COVID-19 on TB care becomes imperative to devise a tailored program for managing TB amidst future pandemics, natural disasters, and conflict crises., Methods: A mixed-methods study design was utilized, encompassing a randomly selected 10 health centers (HCs) and 3 hospitals among government owned 98 HCs and 5 hospitals in Addis Ababa, Ethiopia. All TB patients who were on follow-up during the study period were included. The study period was from March 4, 2020, to December 4, 2020, with the corresponding period of March 4, 2019, to December 4, 2019, serving as the baseline for comparison. Quantitative data were gathered from TB patients' medical registries, laboratory registries, and treatment follow-up charts. Complementary qualitative data were acquired through in-depth interviews. Both qualitative and quantitative data were collected from January 17, 2022 to May 13, 2022., Results: Following the onset of the pandemic, there was a notable and statistically significant decline in both the detection of TB cases and the number of positive results across all study sites. Bacteriological TB tests reduced from 5837 to 2126 patients, and TB-positive cases decreased from 500 to 218, representing declines of 63.6% and 56.4%, respectively. The overall number of TB patients undergoing treatment also experienced a decrease from 1431 to 1051, marking a 26.6% reduction. Additionally, there was a 10% increase in the proportion of extra-pulmonary TB cases. The impact of the pandemic extended to TB treatment outcomes, with adverse effects on cure rates, death rates, loss of follow-up, and medication adherence. The apprehension of contracting COVID-19 and the implementation of isolation measures contributed to a decline in healthcare-seeking behaviors among patients, fostering negative perceptions and practices among healthcare workers. The challenges further exacerbated due to a shortage of personal protective equipment, a lack of rapid diagnostic test tools, clinical presentations resembling COVID-19, and a shift in government policies. These factors collectively posed significant obstacles to effective TB care during the pandemic., Conclusion: The profound impact of COVID-19 on critical TB care service indicators, including TB detection, treatment initiation, and treatment outcomes, underscores the need for immediate and collaborative measures. It is imperative to implement strategies that ensure the resumption of all TB care services concurrently with efforts to control COVID-19. A comprehensive and coordinated approach is essential to mitigate the adverse effects of the pandemic on TB management and safeguard public health., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nasir 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.)

Addison's disease (AD), or primary adrenal insufficiency, was first described by Thomas Addison in patients with adrenal tuberculosis (TB). Over the past several decades, along with the introduction of antituberculous treatment (ATT), the incidence of both has declined. The most common symptoms are nonspecific, leading to delayed diagnosis; patients may first present with a life-threatening crisis. Here, we report a case of AD that, upon further workup, was found to be due to one of the most common infections in India-TB., (© Journal of the Association of Physicians of India 2024.)

India contributes to 26% of the global tuberculosis (TB) burden, with very high mortality and morbidity. The exact incidence of disseminated TB cannot be established among the general population but accounts for <2% of cases among immunocompromised hosts and constitutes 20% of all extrapulmonary TB cases. Disseminated TB has a very high mortality rate of around 25-30%. Miliary TB, a disseminated form, is another entity of TB that poses a health burden due to its difficulty in diagnosis. This entity usually presents with subclinical symptoms and poses a diagnostic challenge in the absence of specific diagnostic tests. We present a case of a young female with epistaxis and thrombocytopenia who was diagnosed with disseminated TB [miliary, bone cyst, bone marrow (BM) involvement]., (© Journal of the Association of Physicians of India 2024.)

Background: Tuberculous pleurisy (TP) is one of the most common types of extrapulmonary tuberculosis, often secondary to tuberculosis (TB). Clinical and imaging manifestations of non-tuberculous mycobacterial pulmonary diseases (NTM-PD) are usually similar to those of tuberculosis. Because of their similarity and the high incidence of tuberculosis, non-tuberculous mycobacterial infections are often overlooked for a long time. Especially in people without immunodeficiency., Methods: Mycobacterium tuberculosis (MTB) in pleural effusion was found by metagenomic next-generation sequencing (mNGS). During anti-tuberculosis treatment, mNGS of lung tissue by ultrasound-guided percutaneous lung puncture revealed that this patient had combined NTM-PD., Results: Mycobacterium chelonae (M. chelonae) was detected by mNGS, and after anti-NTM treatment, the patient's chest CT showed that the inflammation was absorbed more than before, and the patient's symptoms improved., Conclusions: When TB is poorly treated with standardized anti-tuberculosis therapy, comorbid non-tuberculous mycobacterial infections may be considered, and mNGS may complement traditional pathogenetic testing.

Competing Interests: We declare no competing interests.

Background: Drug-resistant tuberculosis (DR-TB) remains a threat to public health. Shorter regimens have been proposed as potentially valuable treatments for multidrug or rifampicin resistant tuberculosis (MDR/RR-TB). We undertook a systematic review and network meta-analysis to evaluate the efficacy and safety of shorter MDR/RR-TB regimens., Methods: We searched PubMed/MEDLINE, Cochrane Center for Clinical Trials (CENTRAL), Scopus, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, US Food and Drug Administration, and Chinese Clinical Trial Registry for primary articles published from 2013 to July 2023. Favorable (cured and treatment completed) and unfavorable (treatment failure, death, loss to follow-up, and culture conversion) outcomes were assessed as the main efficacy outcomes, while adverse events were assessed as the safety outcomes. The network meta-analysis was performed using R Studio version 4.3.1 and the Netmeta package. The study protocol adhered to the PRISMA-NMA guidelines and was registered in PROSPERO (CRD42023434050)., Result: We included 11 eligible studies (4 randomized control trials and 7 cohorts) that enrolled 3,548 patients with MDR/RR-TB. Treatment with a 6-month combination of BdqLzdLfxZTrd/Eto/H had two times more favorable outcomes [RR 2.2 (95% CI 1.22, 4.13), P = 0.0094], followed by a 9-11 month combination of km/CmMfx/LfxPtoCfzZEHh [RR1.67 (95% CI 1.45, 1.92), P < 0.001] and a 6-month BdqPaLzdMfx [RR 1.64 (95% CI 1.24, 2.16), P < 0.0005] compared to the standard longer regimens. Treatment with 6 months of BdqPaLzdMfx [RR 0.33 (95% CI 0.2, 0.55), P < 0.0001] had a low risk of severe adverse events, followed by 6 months of BdqPaLzd [RR 0.36 (95% CI 0.22, 0.59), P ≤ 0.001] and BdqPaLzdCfz [RR 0.54 (95% CI 0.37, 0.80), P < 0.0001] than standard of care., Conclusion: Treatment of patients with RR/MDR-TB using shorter regimens of 6 months BdqLzdLfxZTrd/Eto/H, 9-11 months km/CmMfx/LfxPtoCfzZEHh, and 6 months BdqPaLzdMfx provides significantly higher cure and treatment completion rates compared to the standard longer MDR/RR-TB. However, 6BdqPaLzdMfx, 6BdqPaLzd, and 6BdqPaLzdCfz short regimens are significantly associated with decreased severity of adverse events. The findings are in support of the current WHO-recommended 6-month shorter regimens., (© 2024. The Author(s).)