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BackgroundPoor treatment outcomes among people with drug-resistant TB (DR-TB) are a major concern. Heteroresistance (presence of susceptible and resistant Mycobacterium tuberculosis in the same sample) has been identified in some people with TB, but its impact on treatment outcomes is unknown.MethodsWe used targeted deep sequencing to identify mutations associated with DR-TB and heteroresistance in culture samples of 624 people with DR-TB. We evaluated the association between heteroresistance and time to unfavorable treatment outcome using Cox proportional hazards regression.ResultsThe proportion of drug-resistant isolates with a known mutation conferring resistance was lower for streptomycin (45.2%) and second-line injectables (79.1%) than for fluoroquinolones (86.7%), isoniazid (93.2%) and rifampin (96.5%). Fifty-two (8.3%) had heteroresistance, and it was more common for fluoroquinolones (4.6%) than rifampin (2.2%), second-line injectables (1.4%), streptomycin (1.7%), or isoniazid (1.3%). There was no association between heteroresistance and time to unfavorable outcome among people with multidrug-resistant TB (adjusted hazard ratio [aHR] 1.74, 95% CI 0.39-7.72) or pre-extensively DR-TB (aHR 0.65, 95% CI 0.24-1.72).ConclusionsHeteroresistance was relatively common (8.3%) among people with DR-TB in the Philippines. However, we found insufficient evidence to demonstrate an impact on unfavorable treatment outcomes.

Background: Drug resistant tuberculosis (DR-TB) continues to be a significant global public health concern despite the availability of effective TB medicines. Equally, delayed DR-TB treatment initiation is associated with increased morbidity, amplified resistance, transmission risk and poor treatment outcomes. This study aimed to investigate treatment delays and identify predictors of delayed treatment initiation among DR-TB patients in Uganda. Method: A retrospective study was conducted using routine DR-TB national case registration data between January 2012 and December 2019. Stata version 15 was used to run uni-variate analysis to describe patient characteristics using frequencies and percentages; bivariate analysis to identify significant differences in median times to treatment initiation; and logistic regression model was fitted, and adjusted odds ratio (AOR) with 95% confidence interval was used to identify factors associated with DR-TB treatment delay. Results: A total of 2,166 DR-TB patients were included in this study. The median treatment initiation delay was 10 days. Approximately 57% of DR-TB patients experienced delays in starting their treatment beyond the acceptable 7-day timeframe. Being diagnosed as RR-TB [AOR = 1.22; 95% CI: 1.08–1.37], and being a recurrent TB patient [AOR = 1.22; 95% CI: 1.01–1.47] were associated with treatment delays. Patients with previous history of 'lost to follow-up' (LTFU), failure and being diagnosed as Pre-XDR-TB were less inclined to delay DR-TB treatment. Conclusion: Several DR-TB patients experienced treatment delay. The delay was significant among patients diagnosed as RR-TB and those with TB treatment history of recurrent TB. This highlights the need for heightened vigilance among healthcare workers when managing DR-TB patients with a history of past TB treatment and those diagnosed as RR-TB to minimize delays. Furthermore, future research should investigate a comprehensive list of variables influencing the timing of treatment initiation after diagnosis. An in-depth understanding of the effects of these factors can inform targeted interventions to optimize treatment strategies for improved DR-TB patient outcomes. [ABSTRACT FROM AUTHOR]

Background: The global push to eliminate tuberculosis (TB) as a public health threat is increasingly urgent, particularly in high-burden areas like the Oliver Reginald Tambo District Municipality, South Africa. Drug-resistant TB (DR-TB) poses a significant challenge to TB control efforts and is a leading cause of TB-related deaths. This study aimed to assess DR-TB transmission patterns and predict future cases using geospatial and predictive modeling techniques. Methods: A retrospective cross-sectional study was conducted across five decentralized DR-TB facilities in the O.R. Tambo District Municipality from January 2018 to December 2020. Data were obtained from Statistics South Africa, and patient GPS coordinates were used to identify clusters of DR-TB cases via DBSCAN clustering. Hotspot analysis (Getis-Ord Gi) was performed, and two predictive models (Linear Regression and Random Forest) were developed to estimate future DR-TB cases. Analyses were conducted using Python 3.8 and R 4.1.1, with significance set at p < 0.05. Results: A total of 456 patients with DR-TB were enrolled, with 56.1% males and 43.9% females. The mean age was 37.5 (±14.9) years. The incidence of DR-TB was 11.89 cases per 100,000 population, with males being disproportionately affected. Key risk factors included poverty, lack of education, and occupational exposure. The DR-TB types included RR-TB (60%), MDR-TB (30%), Pre-XDR-TB (5%), XDR-TB (3%), and INHR-TB (2%). Spatial analysis revealed significant clustering in socio-economically disadvantaged areas. A major cluster was identified, along with a distinct outlier. The analyses of DR-TB case trends using historical data (2018–2021) and projections (2022–2026) from Linear Regression and Random Forest models reveal historical data with a sharp decline in DR-TB case, from 186 in 2018 to 15 in 2021, highlighting substantial progress. The Linear Regression model predicts a continued decline to zero cases by 2026, with an R2 = 0.865, a mean squared error (MSE) of 507.175, and a mean absolute error (MAE) of 18.65. Conversely, the Random Forest model forecasts stabilization to around 30–50 cases annually after 2021, achieving an R2 = 0.882, an MSE of 443.226, and an MAE of 19.03. These models underscore the importance of adaptive strategies to sustain progress and avoid plateauing in DR-TB reduction efforts. Conclusions: This study highlights the need for targeted interventions in vulnerable populations to curb DR-TB transmission and improve treatment outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background Despite advances in drug-resistant tuberculosis (DR-TB) diagnosis, treatment, and service delivery, individuals with DR-TB often face significant socioeconomic and psychosocial challenges due to limited resources. These challenges can hinder retention in care, undermining the progress made in DR-TB management. As a consequence, advances in DR-TB diagnostics and treatment have not resulted in DR-TB programs meeting the 75% treatment success targets set by the World Health Organization (WHO). Methods We interviewed people with DR-TB who had disengaged from care and their family members to identify barriers and facilitators to retention in care as well as possible strategies to address these barriers. We recruited 16 people with DR-TB and 8 family members from five health facilities in Johannesburg, Gauteng Province, South Africa. All DR-TB patients disengaged from DR-TB care for ≥ 45 days. Semi-structured interviews and focus group discussions were used to collect data, which were analysed through thematic content analysis using a multidimensional adherence model. Results The facilitators of retention in care were positive interactions with health care workers (HCWs), nutritional support, transport from local clinics to DR-TB sites, self-motivation, and emotional support from family members. Barriers to optimal retention in care included a limited understanding of DR-TB disease and treatment, transport challenges, side effects of the medication, pill burden, stigma and discrimination experienced at health care facilities other than DR-TB facilities, food insecurity, and financial difficulties, which included loss of income and a lack of transport money and mental health challenges such as fear, anxiety and feeling lonely and unsupported. Conclusion The findings from this study highlight the need for TB treatment programs to collaborate with people being treated for DR-TB and their families to understand facilitators and barriers to retention in care and how these could be addressed to facilitate optimal retention in care.

Abstract Background Drug-resistant tuberculosis (DR-TB) poses a significant global health challenge and requires treatment with potentially toxic second-line anti-TB drugs. Assessing the health-related quality of life (HRQoL) of DR-TB patients is crucial, given the impact of disease and treatment on their well-being. This study aimed to evaluate HRQoL among DR-TB patients undergoing treatment in Botswana and identify predictors of variability during the treatment period. Methods A cross-sectional study involving almost all the eligible clients in the DR-TB treatment database was conducted at four of the six DR-TB sites in Botswana. The SF-36v2-based questionnaire was administered to all patients receiving treatment between March 2022 and June 2023. Data analysis was performed with QualityMetric Inc., LLC PRO CoRE scoring software and Stata 13.1 for the HRQoL scoring and regression analyses, respectively. A score ≤ 47 on the norm-based scoring (NBS) indicated poor HRQoL. Shorter, all-oral DR-TB regimens were introduced since 2018 but Botswana had not yet fully implemented those in the years 2022/2023. Patients had to go on treatment for 18–24 months during the time of the study. Results Seventy-two of the 81 eligible participants were enrolled. Participants on treatment for 13–24 months exhibited better HRQoL scores (53.3 ± 8.4) than those in the initial (0–12 months, 46.9 ± 10.8) and latter phases of treatment (> 24 months, 44.3 ± 10.1) for the Physical Component Summary (PCS) even though it was not statistically significant (p = 0.0996). The mental component summary (MCS) scores were 41.6 ± 11.3, 51.6 ± 7.8, and 41.3 ± 10.7 for 0–12, 13–24, and > 24 months, respectively, with significant differences observed for the MCS (p = 0.0097). Multivariate analysis identified renal impairment as a predictor of PCS variability, while alcohol consumption, prior TB treatment, and lung cavity on chest X-ray imaging predicted MCS variability. Conclusion DR-TB patients in Botswana demonstrated comparable or improved HRQoL (> 47 NBS) in their second year (13–24 months) of treatment, contrasting with poorer HRQoL scores in the initial and final years for both the PCS and MCS. The findings underscore the necessity for tailored psychosocial support, advocated for its integration into the Botswana National TB Program as a pilot initiative before widespread implementation.

BACKGROUND: Poor treatment outcomes among people with drug-resistant TB (DR-TB) are a major concern. Heteroresistance (presence of susceptible and resistant Mycobacterium tuberculosis in the same sample) has been identified in some people with TB, but its impact on treatment outcomes is unknown. METHODS: We used targeted deep sequencing to identify mutations associated with DR-TB and heteroresistance in culture samples of 624 people with DR-TB. We evaluated the association between heteroresistance and time to unfavorable treatment outcome using Cox proportional hazards regression. RESULTS: The proportion of drug-resistant isolates with a known mutation conferring resistance was lower for streptomycin (45.2%) and second-line injectables (79.1%) than for fluoroquinolones (86.7%), isoniazid (93.2%) and rifampin (96.5%). Fifty-two (8.3%) had heteroresistance, and it was more common for fluoroquinolones (4.6%) than rifampin (2.2%), second-line injectables (1.4%), streptomycin (1.7%), or isoniazid (1.3%). There was no association between heteroresistance and time to unfavorable outcome among people with multidrug-resistant TB (adjusted hazard ratio [aHR] 1.74, 95% CI 0.39–7.72) or pre-extensively DR-TB (aHR 0.65, 95% CI 0.24–1.72). CONCLUSIONS: Heteroresistance was relatively common (8.3%) among people with DR-TB in the Philippines. However, we found insufficient evidence to demonstrate an impact on unfavorable treatment outcomes.

BACKGROUND: Since 2012, WHO has supported countries in scaling up programmatic management of drug-resistant tuberculosis (PMDT). We assessed progress and challenges to formulate recommendations for improvement. METHODS: We reviewed the regional Green Light Committee (rGLC)mission reports and analysed data to describe the progression of programme indicators. RESULTS: The proportion of TB patients initially tested using Xpert MTB/RIF rose from 5% in 2017 to 54% in 2022. Testing for rifampicin-resistant TB (RR-TB) increased from 4% in 2015 to 68% in 2022 among new patients and from 17% in 2015 to 94% in 2022 among those previously treated. Consequently, in 2021–2022, the number of multidrug-resistant (MDR)/RR-TB patients diagnosed increased by 29% and 84% of them were treated, accounting for 22% of estimated cases. By 2023, fourteen countries had implemented all-oral regimens, with three initiating the 6-month bedaquiline, pretomanid, linezolid, and moxifloxacin regimen (BPaL(M)). MDR/RR-TB treatment success increased from 64% in 2017 to 73% in 2020. CONCLUSIONS: Eastern Mediterranean Region countries progressed in PMDT using Xpert MTB/RIF, increased diagnosis and treatment of MDR/RR-TB patients using all-oral regimens, and improved treatment success. They must now enhance diagnostic capacity using WHO-recommended diagnostics, decentralise services while integrating them into primary health care, and prioritise the BPaL(M) regimen.

SETTING: Multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB) is now endemic in the National Capital District (NCD), Papua New Guinea. Loss to follow-up (LTFU) is a challenge. OBJECTIVE: To evaluate and identify risk factors for LTFU, including pre-treatment LTFU, in adults with MDR/RR-TB at Port Moresby General Hospital (PMGH). DESIGN: A retrospective analysis of treatment initiation in adults diagnosed with MDR/RR-TB (2018–2022) and outcomes for a cohort treated for MDR/RR-TB (2014-2019). We assessed the factors associated with LTFU using multivariate logistic regression. RESULTS: Of 95 patients diagnosed with MDR/RR-TB at PMGH from 2018 to 2022, 21 (22%) were lost to follow-up before treatment. Of the 658 adults who initiated treatment for MDR/RR-TB at PMGH from 2014 to 2019, 161 (24%) were lost to follow-up during treatment. A higher proportion of patients on injectable-containing long regimens (110/404, 27%) were lost to follow-up than those on the all-oral regimen containing bedaquiline (13/66, 12%). Treatment loss to follow-up was associated with age (35–54 years age group: aOR 0.49, 95% CI 0.32–0.77; 55–75 years age group: aOR 0.42, 95% CI 0.19–0.90; compared to the 15–34 years age group), residence outside of NCD (aOR 1.79, 95% CI 1.04–3.06), and year of treatment initiation. CONCLUSION: Pre-treatment LTFU requires programmatic focus. Shorter oral regimens and decentralised services may address the reasons for higher LTFU in younger people and people living outside NCD.

Background: Drug-resistant tuberculosis (DR-TB) poses a significant global health challenge and requires treatment with potentially toxic second-line anti-TB drugs. Assessing the health-related quality of life (HRQoL) of DR-TB patients is crucial, given the impact of disease and treatment on their well-being. This study aimed to evaluate HRQoL among DR-TB patients undergoing treatment in Botswana and identify predictors of variability during the treatment period. Methods: A cross-sectional study involving almost all the eligible clients in the DR-TB treatment database was conducted at four of the six DR-TB sites in Botswana. The SF-36v2-based questionnaire was administered to all patients receiving treatment between March 2022 and June 2023. Data analysis was performed with QualityMetric Inc., LLC PRO CoRE scoring software and Stata 13.1 for the HRQoL scoring and regression analyses, respectively. A score ≤ 47 on the norm-based scoring (NBS) indicated poor HRQoL. Shorter, all-oral DR-TB regimens were introduced since 2018 but Botswana had not yet fully implemented those in the years 2022/2023. Patients had to go on treatment for 18–24 months during the time of the study. Results: Seventy-two of the 81 eligible participants were enrolled. Participants on treatment for 13–24 months exhibited better HRQoL scores (53.3 ± 8.4) than those in the initial (0–12 months, 46.9 ± 10.8) and latter phases of treatment (> 24 months, 44.3 ± 10.1) for the Physical Component Summary (PCS) even though it was not statistically significant (p = 0.0996). The mental component summary (MCS) scores were 41.6 ± 11.3, 51.6 ± 7.8, and 41.3 ± 10.7 for 0–12, 13–24, and > 24 months, respectively, with significant differences observed for the MCS (p = 0.0097). Multivariate analysis identified renal impairment as a predictor of PCS variability, while alcohol consumption, prior TB treatment, and lung cavity on chest X-ray imaging predicted MCS variability. Conclusion: DR-TB patients in Botswana demonstrated comparable or improved HRQoL (> 47 NBS) in their second year (13–24 months) of treatment, contrasting with poorer HRQoL scores in the initial and final years for both the PCS and MCS. The findings underscore the necessity for tailored psychosocial support, advocated for its integration into the Botswana National TB Program as a pilot initiative before widespread implementation. [ABSTRACT FROM AUTHOR]

Drug-resistant tuberculosis (DR-TB) and HIV coinfection present a conundrum to public health globally and the achievement of the global END TB strategy in 2035. A descriptive, retrospective review of medical records of patients, who were diagnosed with DR-TB and received treatment, was conducted. Student's t-test was performed to assess differences between two means and ANOVA between groups. The Chi-square test with or without trend or Fischer's exact test was used to test the degree of association of categorical variables. Logistic regression was used to determine predictors of DR-TB treatment outcomes. A decision tree classifier, which is a supervised machine learning algorithm, was also used. Python version 3.8. and R version 4.1.1 software were used for data analysis. A p-value of 0.05 with a 95% confidence interval (CI) was used to determine statistical significance. A total of 456 DR-TB patients were included in the study, with more male patients (n = 256, 56.1%) than female patients (n = 200, 43.9%). The overall treatment success rate was 61.4%. There was a significant decrease in the % of patients cured during the COVID-19 pandemic compared to the pre-pandemic period. Our findings showed that machine learning can be used to predict TB patients' treatment outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Isoniazid (INH, H) resistance is the most common drug-resistant TB pattern, with treatment success rates lower than those in drug-susceptible TB. The WHO recommends a 6-month regimen of rifampicin (RIF, R), ethambutol (EMB, E), pyrazinamide (PZA, Z), and levofloxacin (Lfx) (6REZLfx) for INH-resistant, RIF-susceptible TB (HRRS-TB). Uzbekistan has a high burden of TB (62/100,000 population) and multidrug-resistant TB (12/100,000 population). METHODS: We conducted a retrospective, descriptive study of microbiologically confirmed HRRS-TB using routinely collected programmatic data from 2009 to 2020. RESULTS: We included 854 HRRS-TB cases. Treatment success was 80.2% overall. For REZLfx, the treatment success rate was 92.0% over a short treatment duration, with no amplifications to RIF or second-line anti-TB drug resistance. We documented 46 regimens with REZLfx plus linezolid (success 87.0%) and 539 regimens using kanamycin or capreomycin (success 76.6%). We identified 37 treatment failures (4.3%), 30 deaths (3.5%), 25 resistance amplifications (2.9%), including eight to RIF (0.9%), and 99 lost to follow-up (LTFU) cases (11.6%). Unsuccessful outcomes were more common with older age, diabetes, chest X-ray cavities, smear positivity, smear-positive persistence, and male sex. LTFU was more common with injection-containing regimens. CONCLUSIONS: REZLfx is a safe and effective first-line treatment for INH-resistant, RIF-susceptible TB. Treatment success was lower and LTFU was higher for injection-containing regimens.

Introduction: Pakistan has the highest burden of Tuberculosis (TB) worldwide and the 5th highest prevalence of multi- drug resistant (MDR) TB worldwide. There is scarce data on the socioeconomic characteristics and factors associated with the patients presenting with drug resistant-TB in Pakistani context. Aims & Objectives: To determine the association of different variables with rifampin resistance (RR) in new and previously treated cases of pulmonary (PTB) and extra-pulmonary TB (EPTB) Place and Duration of Study: It was a cross-sectional study conducted at Gulab Devi Hospital Lahore, a tertiary care trust hospital. Data was collected from Oct 2021 to December 31, 2021. Material & Method: By applying convenient sampling technique, 202 individuals were interviewed, and data was recorded on a self-constructed questionnaire. Data was analyzed using SPSS version 24.0. Frequency tables were generated for sociodemographic variables as well as the site of TB and Chi square test was applied to find association between categorical variables. P value of

This document summarizes a scoping review on the use of linezolid in the treatment of drug-resistant tuberculosis (DR-TB). The review found that myelosuppression, particularly anemia, was a common side effect of linezolid treatment in DR-TB patients. Risk factors for myelosuppression included HIV co-infection, age, and high exposure to linezolid. Regular monitoring of hematologic parameters is recommended during linezolid treatment, especially in patients with these risk factors. The document also provides insights into dosing strategies, pharmacokinetics, and the importance of considering factors such as age and renal function when using linezolid in TB treatment. [Extracted from the article]

Aim: To determine the bacteriological conversion rate after 6 months of Delamanid (DLM) based treatment in children with drug-resistant tuberculosis (DR-TB) and determine factors associated with bacteriological conversion. Methods: This is a descriptive retrospective study done in children between the age of 6-17 years with DR-TB who received DLM-based therapy from October 2018 to May 2021. The drug resistance pattern of TB was detected using Xpert RIF/MTB and phenotypic drug sensitivity testing (DST) on TB-MGIT culture reports. Follow-up sputum TB MGIT culture was carried out monthly after DLM initiation for 6 months. Factors associated with sputum bacteriological conversion such as age, gender, pulmonary TB (PTB) versus disseminated TB, unilateral or bilateral lung involvement, type of DR-TB, prior treatment failure, and type of DR-TB regimen were analyzed. Results: Sixty patients received DLM of which two had extrapulmonary TB (EPTB) and sputum conversion could not be assessed. The mean age at presentation was 12.69 ± 3.03 years. Five patients (8.3%) died while on DLM treatment. On follow-up, 8 (13.7%) out of 58 patients had no sputum bacteriological conversion after 6 months of DLM initiation of which three patients were on salvage therapy; 46 (79.3%) had sputum bacteriological conversion within 6 months of DLM initiation. Conclusion: Sputum bacteriological conversion rate was almost 80% at the end of 6 months of DLM-based treatment.

Razia Hassan-Moosa,1,2 Kegaugetswe Wilhemina Motsomi,1 Radhamoney Narasimmulu,1 Aida Sivro,1,3– 5 Kevindra K Naidu,1 Ayesha BM Kharsany,1,3 Natasha Samsunder,1 Rubeshan Perumal,1,2 Kogieleum Naidoo1,2 1Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa; 2MRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa; 3Department of Medical Microbiology, University of KwaZulu-Natal, Durban, South Africa; 4JC Wilt Infectious Disease Research Centre, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada; 5Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, CanadaCorrespondence: Kegaugetswe Wilhemina Motsomi, Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal Nelson R Mandela School of Medicine, Private Bag X7, Congella, Durban, 4013, South Africa, Email pinky.motsomi@caprisa.orgBackground: Coronavirus disease (COVID-19) potentially exacerbates drug-resistant tuberculosis (DR-TB). We describe the clinical presentation and outcomes of three patients with human immunodeficiency virus (HIV), DR-TB and COVID-19.Case One: A virologically suppressed 31-year-old man on antiretroviral therapy (ART) and multidrug-resistant (MDR)-TB treatment presented with mild COVID-19 and was hospitalised for 10 days of clinical monitoring, despite being clinically stable with normal baseline inflammatory markers. Severe acute respiratory syndrome coronavirus polymerase chain reaction (SARS-CoV-2 PCR) positivity persisted at Day 28.Case Two: A virologically suppressed 37-year-old woman on ART and MDR-TB treatment presented with moderate COVID-19. Baseline inflammatory markers were raised, and dexamethasone and azithromycin were initiated with good clinical improvement. SARS-CoV-2 PCR positivity persisted at Day 28.Case Three: A viraemic 24-year-old woman on second-line ART and MDR-TB treatment, presented with mild COVID-19 disease, normal oxygenation and normal inflammatory markers, and remained clinically stable with negative SARS-CoV-2 PCR at Days 14 and 28.Conclusion: Screening for SARS-CoV-2 infection is advised for DR-TB patients with new or worsening respiratory symptoms.Keywords: HIV, DR-TB, COVID-19, case reviews, screening, transmission

Drug-resistant tuberculosis (DR-TB) and HIV coinfection present a conundrum to public health globally and the achievement of the global END TB strategy in 2035. A descriptive, retrospective review of medical records of patients, who were diagnosed with DR-TB and received treatment, was conducted. Student’s t-test was performed to assess differences between two means and ANOVA between groups. The Chi-square test with or without trend or Fischer’s exact test was used to test the degree of association of categorical variables. Logistic regression was used to determine predictors of DR-TB treatment outcomes. A decision tree classifier, which is a supervised machine learning algorithm, was also used. Python version 3.8. and R version 4.1.1 software were used for data analysis. A p-value of 0.05 with a 95% confidence interval (CI) was used to determine statistical significance. A total of 456 DR-TB patients were included in the study, with more male patients (n = 256, 56.1%) than female patients (n = 200, 43.9%). The overall treatment success rate was 61.4%. There was a significant decrease in the % of patients cured during the COVID-19 pandemic compared to the pre-pandemic period. Our findings showed that machine learning can be used to predict TB patients’ treatment outcomes.

Aim: To determine the bacteriological conversion rate after 6 months of Delamanid (DLM) based treatment in children with drug-resistant tuberculosis (DR-TB) and determine factors associated with bacteriological conversion. Methods: This is a descriptive retrospective study done in children between the age of 6-17 years with DR-TB who received DLM-based therapy from October 2018 to May 2021. The drug resistance pattern of TB was detected using Xpert RIF/MTB and phenotypic drug sensitivity testing (DST) on TB-MGIT culture reports. Follow-up sputum TB MGIT culture was carried out monthly after DLM initiation for 6 months. Factors associated with sputum bacteriological conversion such as age, gender, pulmonary TB (PTB) versus disseminated TB, unilateral or bilateral lung involvement, type of DR-TB, prior treatment failure, and type of DR-TB regimen were analyzed. Results: Sixty patients received DLM of which two had extrapulmonary TB (EPTB) and sputum conversion could not be assessed. The mean age at presentation was 12.69 ± 3.03 years. Five patients (8.3%) died while on DLM treatment. On follow-up, 8 (13.7%) out of 58 patients had no sputum bacteriological conversion after 6 months of DLM initiation of which three patients were on salvage therapy; 46 (79.3%) had sputum bacteriological conversion within 6 months of DLM initiation. Conclusion: Sputum bacteriological conversion rate was almost 80% at the end of 6 months of DLM-based treatment. [ABSTRACT FROM AUTHOR]

Background: South Africa adopted the decentralised Drug Resistant Tuberculosis (DR-TB) care model in 2011 with a view of improving clinical outcomes. Aim: This study explores the experiences and perceptions of patients and family members on the effectiveness of a decentralised community DR-TB care model in the Oliver Reginald Kaizana (OR) Tambo district municipality of the Eastern Cape, South Africa. Method: In this phenomenological qualitative research design, a semi-structured interview with prompts was conducted on 30 participants (15 patients and 15 family members). Framework approach to thematic content analysis was adopted for qualitative data analysis. Results: Four themes emerged from the patients’ interviews: adequate knowledge of DR-TB and its transmission, fear of death and isolation, long travel distances, and exorbitant transportation cost. A ‘ready’ health system influenced the effectiveness of community DR-TB management, while interviews with family members yielded five themes: misconceptions about DR-TB, rapid diagnosis and adherence counselling, long travel distances, activated healthcare workers, and little role of traditional healer. Conclusion: A perceived effectiveness of a community DR-TB care model in the OR Tambo district was demonstrated through the quality and comprehensiveness of care rendered by a ‘ready’ health system with activated health care workers (HCWs) who provided robust support and adequate knowledge of DR-TB and its treatment/side effects. However, misconceptions about DR-TB, long travel distances to treatment facilities, high cost of transportation and stigma remained challenging for most patients and family members. Contribution: This study provides insight into the lived experiences of a decentralised community DR-TB care model in the OR Tambo district in 2020.

Background. Progressive interventions have recently improved programmatic outcomes in drug-resistant tuberculosis (DR-TB) care in South Africa (SA). Amidst these, a shorter regimen was introduced in 2017 with weak evidence, and has shown mixed results. Outcomes still fall short of national targets, and the coronavirus disease 2019 pandemic has undermined progress to date. Objectives. To describe the outcomes of participants treated for DR-TB using a shorter, compared with a longer, regimen in a deeply rural SA setting, and to explore other factors affecting these outcomes. Methods. This retrospective cohort study describes outcomes in short and long DR-TB treatment regimens, over 5 years, at two rural treatment sites in SA. Characteristics were analysed for outcome correlates using multivariable logistic regression models. Results. Of 282 treatment episodes, 62% were successful, with higher success in shorter (69%) compared with longer regimens (58%). Mortality was approximately 21% in both groups. Characteristics included high proportions of HIV co-infection (61%). Injectables (adjusted odds ratio (aOR) 3.00, 95% confidence interval (CI) 1.48 - 6.09), bedaquiline (aOR 3.16, 95% CI 1.36 - 7.35), increasing age (aOR 0.97, 95% CI 0.95 - 0.99) and HIV viraemia defined as final HIV-RNA viral load >1 000 copies/mL (aOR 0.16, 95% CI 0.07 - 0.37) were all significantly and independently associated with treatment success. Injectables (aOR 0.22, 95% CI 0.08 - 0.57), bedaquiline (aOR 0.05, 95% CI 0.01 - 0.19), increasing age (aOR 1.09, 95% CI 1.05 - 1.13), extra-pulmonary TB (aOR 8.15, 95% CI 1.62 - 41.03) and HIV viraemia (aOR 9.20, 95% CI 3.22 - 26.24) were all significantly and independently associated with mortality. Conclusion. In a rural context, treating DR-TB amid limited resources and a high burden of HIV co-infection, we found that after considering controls, a short regimen was no different to a longer regimen in terms of success or mortality. Therefore, by alleviating burdens on multiple stakeholders, a short regimen is likely to be favourable for rural patients, clinicians, and healthcare systems. Besides other previously described correlates of outcomes, HIV viraemia emerged as a novel marker for reliably predicting poor outcomes in DR-TB with HIV co-infection, and a pragmatic target for intervention.

Human migration and the ever-changing geopolitical scenarios are redefining the epidemiology and the management of tuberculosis (TB), especially in low-TB burden countries welcoming high rates of people from high-TB burden countries. We conducted an observational retrospective mono-centric study in a Northern-Italy TB reference centre from 1 January 1990 to 31 December 2019, focusing on the differences in epidemiology, resistance patterns and treatment outcomes between Italians and migrants with active TB. Data were collected from medical records. A total of 10555 patients were included, 4614 Italians and 5941 migrants. Among migrants, higher rates of rifampin-resistant (RR) or multidrug-resistant (MDR) TB were reported, as well as higher rates of loss to follow-up. Among Italians, higher mortality rates and a higher number of extrapulmonary TB cases were found. Our study describes one of the largest cohorts of patients with active TB in Italy, highlighting the need for tailored approaches in native and migrant populations. [ABSTRACT FROM AUTHOR]

A rapid diagnosis of drug-resistant tuberculosis (TB) is critical for early initiation of effective therapy. Molecular testing with line probe assays (MTBDRplus and MTBDRsl) on culture isolates has been available for some time and significantly reduces the time to diagnosis of drug resistance. However, routine use of this test directly on sputum is less common. As part of enrollment screening procedures for tuberculosis clinical trials conducted in Hanoi, Vietnam, we evaluated the feasibility and performance of line probe assay (LPA) testing directly on sputum samples from 315 participants with no prior history of TB treatment. Test performance characteristics for the detection of rifampin (RIF) and isoniazid (INH) drug resistance as compared to culture-based drug susceptibility testing (DST) reference standard were calculated. LPA demonstrated high sensitivity and specificity for the diagnosis of drug resistance. Scaling up molecular testing on sputum as part of time-sensitive clinical trial screening procedures in high TB burden settings is feasible and will reduce both time to initiation of appropriate therapy and the risk of late exclusions due to microbiologic ineligibility.

Abstract Background This retrospective cohort study assessed benefits and risks of bedaquiline treatment in multidrug-resistant-tuberculosis (MDR-TB) combination therapy by evaluating safety, effectiveness, drug utilization and emergence of resistance to bedaquiline. Methods Data were extracted from a register of South African drug-resistant-tuberculosis (DR-TB) patients (Electronic DR-TB Register [EDRWeb]) for newly diagnosed patients with MDR-TB (including pre-extensively drug-resistant [XDR]-TB and XDR-TB and excluding rifampicin-mono-resistant [RR]-TB, as these patients are by definition not multidrug-resistant), receiving either a bedaquiline-containing or non-bedaquiline-containing regimen, at 14 sites in South Africa. Total duration of treatment and follow-up was up to 30 months, including 6 months’ bedaquiline treatment. WHO treatment outcomes within 6 months after end-of-treatment were assessed in both patient groups. Longer term mortality (up to 30 months from treatment start) was evaluated through matching to the South African National Vital Statistics Register. Multivariable Cox proportional hazards analyses were used to predict association between receiving a bedaquiline-containing regimen and treatment outcome. Results Data were extracted from EDRWeb for 5981 MDR-TB patients (N = 3747 bedaquiline-treated; N = 2234 non-bedaquiline-treated) who initiated treatment between 2015 and 2017, of whom 40.7% versus 80.6% had MDR-TB. More bedaquiline-treated than non-bedaquiline-treated patients had pre-XDR-TB (27.7% versus 9.5%) and XDR-TB (31.5% versus 9.9%) per pre-2021 WHO definitions. Most patients with treatment duration data (94.3%) received bedaquiline for 6 months. Treatment success (per pre-2021 WHO definitions) was achieved in 66.9% of bedaquiline-treated and 49.4% of non-bedaquiline-treated patients. Death was reported in fewer bedaquiline-treated (15.4%) than non-bedaquiline-treated (25.6%) patients. Bedaquiline-treated patients had increased likelihood of treatment success and decreased risk of mortality versus non-bedaquiline-treated patients. In patients with evaluable drug susceptibility testing data, 3.5% of bedaquiline-susceptible isolates at baseline acquired phenotypic resistance. Few patients reported bedaquiline-related treatment-emergent adverse events (TEAEs) (1.8%), TEAE-related bedaquiline discontinuations (1.4%) and QTcF values > 500 ms (2.5%) during treatment. Conclusion Data from this large cohort of South African patients with MDR-TB showed treatment with bedaquiline-containing regimens was associated with survival and effectiveness benefit compared with non-bedaquiline-containing regimens. No new safety signals were detected. These data are consistent with the positive risk–benefit profile of bedaquiline and warrant continued implementation in combination therapy for MDR-TB treatment.

Yuanping Pan, Yingying Yu, Jiachen Lu, Yaohui Yi, Xiaofeng Dou, Ling Zhou School of Public Health, Dalian Medical University, Dalian, 116000, People’s Republic of ChinaCorrespondence: Ling Zhou, School of Public Health, Dalian Medical University, 9 West Section, Lvshun South Road, Dalian, Liaoning Province, People’s Republic of China, Tel +86 411 8611 0368, Email zhouling0609@163.comPurpose: The emergence of drug-resistant tuberculosis (DR-TB) represents a threat to the control of tuberculosis. This study aimed to estimate the patterns and trends of DR-TB in patients with suspected DR-TB. In addition, risk factors for multidrug-resistant tuberculosis (MDR-TB) were identified among suspected DR-TB patients in Dalian, China.Patients and Methods: A total of 5661 patients with suspected DR-TB from Jan 1, 2013 to Dec 31, 2020 were included in the final analysis. The resistance pattern of all resistant strains was determined by drug susceptibility testing (DST) using the conventional Lowenstein-Jensen Proportion Method (LJ). DR-TB trends were estimated from 2013 to 2020. During the research period, the chi-square test was employed to analyze the significance of linear drug-resistance trends across time. Bivariate and multivariate logistic regression were performed to assess factors associated with MDR-TB.Results: From 2013 to 2020, the resistance rates of rifampicin (RFP) and isoniazid (INH) decreased significantly, whereas the resistance rates of ethambutol (EMB) and streptomycin (SM) increased in patients with suspected DR-TB. From 2013 to 2020, the prevalence of DR-TB decreased in all patients from 34.71% to 28.01% with an average annual decrease of 3.02%. Among new cases, from 2013 to 2020, the prevalence of DR-TB (from 26.67% to 24.75%), RFP-resistant TB (RR-TB) (from 15.09% to 3.00%) and MDR-TB (from 6.08% to 2.62%) showed a significant downward trend. Among patients with a previous treatment history, DR-TB (from 54.70% to 37.50%), RR-TB (from 44.16% to 11.49%) and MDR-TB (from 26.90% to 10.34%) showed a significant downward trend from 2013 to 2020. Males (AOR 1.28, 95% CI 1.035– 1.585), patients 45 to 64 years of age (AOR 1.75, 95% CI 1.342– 2.284), patients 65 years and older (AOR 1.65, 95% CI 1.293– 2.104), rural residents (AOR 1.24, 95% CI 1.014– 1.519) and a previous treatment history (AOR 3.94, 95% CI 3.275– 4.741) were risk factors for MDR-TB.Conclusion: The prevalence of DR-TB, RR-TB and MDR-TB was significantly reduced from 2013 to 2020. Considerable progress has been made in the prevention and treatment of DR-TB during this period. However, the increasing rate of drug resistance in EMB and SM should be taken seriously. Suspected DR-TB patients who are male, older than 45 years of age, live in rural areas, and have a history of TB treatment should be given priority by health care providers.Keywords: Mycobacterium tuberculosis, DR-TB, RR-/MDR-TB, prevalence, associated factors

Background: This retrospective cohort study assessed benefits and risks of bedaquiline treatment in multidrug-resistant-tuberculosis (MDR-TB) combination therapy by evaluating safety, effectiveness, drug utilization and emergence of resistance to bedaquiline.Methods: Data were extracted from a register of South African drug-resistant-tuberculosis (DR-TB) patients (Electronic DR-TB Register [EDRWeb]) for newly diagnosed patients with MDR-TB (including pre-extensively drug-resistant [XDR]-TB and XDR-TB and excluding rifampicin-mono-resistant [RR]-TB, as these patients are by definition not multidrug-resistant), receiving either a bedaquiline-containing or non-bedaquiline-containing regimen, at 14 sites in South Africa. Total duration of treatment and follow-up was up to 30 months, including 6 months' bedaquiline treatment. WHO treatment outcomes within 6 months after end-of-treatment were assessed in both patient groups. Longer term mortality (up to 30 months from treatment start) was evaluated through matching to the South African National Vital Statistics Register. Multivariable Cox proportional hazards analyses were used to predict association between receiving a bedaquiline-containing regimen and treatment outcome.Results: Data were extracted from EDRWeb for 5981 MDR-TB patients (N = 3747 bedaquiline-treated; N = 2234 non-bedaquiline-treated) who initiated treatment between 2015 and 2017, of whom 40.7% versus 80.6% had MDR-TB. More bedaquiline-treated than non-bedaquiline-treated patients had pre-XDR-TB (27.7% versus 9.5%) and XDR-TB (31.5% versus 9.9%) per pre-2021 WHO definitions. Most patients with treatment duration data (94.3%) received bedaquiline for 6 months. Treatment success (per pre-2021 WHO definitions) was achieved in 66.9% of bedaquiline-treated and 49.4% of non-bedaquiline-treated patients. Death was reported in fewer bedaquiline-treated (15.4%) than non-bedaquiline-treated (25.6%) patients. Bedaquiline-treated patients had increased likelihood of treatment success and decreased risk of mortality versus non-bedaquiline-treated patients. In patients with evaluable drug susceptibility testing data, 3.5% of bedaquiline-susceptible isolates at baseline acquired phenotypic resistance. Few patients reported bedaquiline-related treatment-emergent adverse events (TEAEs) (1.8%), TEAE-related bedaquiline discontinuations (1.4%) and QTcF values > 500 ms (2.5%) during treatment.Conclusion: Data from this large cohort of South African patients with MDR-TB showed treatment with bedaquiline-containing regimens was associated with survival and effectiveness benefit compared with non-bedaquiline-containing regimens. No new safety signals were detected. These data are consistent with the positive risk-benefit profile of bedaquiline and warrant continued implementation in combination therapy for MDR-TB treatment. [ABSTRACT FROM AUTHOR]

Background Although a third of people with tuberculosis (TB) are estimated to be coinfected with helminths, the prevalence is largely unknown among people with drug-resistant TB (DR-TB). We determined the prevalence of helminth coinfection among people with DR-TB in Uganda. Methods In a multicenter, cross-sectional study, eligible Ugandan adults with confirmed DR-TB were consecutively enrolled between July to December 2021 at 4 treatment centers. Sociodemographic data were collected using a questionnaire. Participants underwent anthropometric and blood pressure measurements, and blood samples were evaluated for random blood glucose, glycated hemoglobin, nonfasting lipid profile, human immunodeficiency virus (HIV) infection, and a complete blood count. Fresh stool samples were evaluated for adult worms, eggs, and larvae using direct microscopy after Kato-Katz concentration techniques. Results Of 212 participants, 156 (73.6%) were male, 118 (55.7%) had HIV, and 3 (2.8%) had malaria coinfection. The prevalence of intestinal helminth coinfection was 4.7% (10/212) (95% confidence interval, 2.6%–8.6%). The frequency of helminth infections was Ancylostoma duodenale (n = 4), Schistosoma mansoni (n = 2), Enterobius vermicularis (n = 2), Ascaris lumbricoides (n = 1), and Trichuris trichiura (n = 1). Conclusions The prevalence of helminth coinfection was low among people with DR-TB. More studies are needed to determine the clinical relevance of helminth/DR-TB coinfection. [ABSTRACT FROM AUTHOR]

Objectives: Globally, drug-resistant tuberculosis (DR-TB) is the leading cause of death globally related to antimicrobial resistance, affecting 500,000 emergent cases annually. In 2018, the first United Nations High-Level Meeting (UNHLM) on tuberculosis declared DR-TB a global public health priority. Bold country targets were established for 2018–2022. This study reviews the DR-TB situation in 2018, and the UNHLM target accomplishments in 10 high-burden countries (HBCs). Methods: An ecological descriptive analysis of the top 10 DR-TB HBCs (Bangladesh, China, India, Indonesia, Myanmar, Nigeria, Pakistan, Philippines, Russian Federation, and South Africa), which share 70% of the global DR-TB burden, was undertaken, complemented by a cascade-of-care analysis and a survey gathering additional information on key advances and setbacks 2 years after the UNHLM declaration. Results: Most countries are showing historic advances and are on track for the 2018 and 2019 targets. However, according to the cascade-of-care, none of the countries are capable of providing effective care for 50% of the estimated patients. Increasing levels of fluoroquinolone resistance and access to timely susceptibility testing can jeopardize ongoing adoption of shorter, all-oral treatment regimens. The programmatic management of DR-TB in children remains minimal. Achievements for 2020 and beyond may be affected significantly by the coronavirus disease 2019 (COVID-19) pandemic. Conclusion: Triggered by the COVID-19 pandemic, there is a global risk of recoil in DR-TB care with long-term consequences in terms of deaths, suffering and wider transmission. Investment to support DR-TB services is more important now than ever to meet the aspirations of the UNHLM declaration.

An essential metric for determining the efficacy of tuberculosis (TB) control programs is the evaluation of TB treatment outcomes; this study was conducted to investigate treatment outcomes and associated factors among tuberculosis patients in rural areas of Eastern Cape, South Africa. Assessing treatment outcomes is fundamental to facilitating the End TB Strategy’s set target. Clinic records from 457 patients with DR-TB were examined for data collection while 101 patients were followed up prospectively. Data were analyzed using Stata version 17.0. The odds ratio and 95% confidence interval were calculated to check the association between variables. p ≤ 0.05 was considered statistically significant. Of the 427 participants, 65.8% had successful treatment whilst 34.2% had unsuccessful TB treatment. A total of 61.2% and 39% of the HIV-positive and HIV-negative participants had a successful TB treatment whilst 66% and 34% of both HIV-negative and positive participants had unsuccessful TB treatment. From the 101 patients that were followed up, smokers took longer to have treatment outcomes compared to non-smokers. In the study with HIV/TB co-infection, men predominated. HIV and tuberculosis co-infection made therapy difficult with unfavorable effects on TB management. The treatment success rate (65.8%) was lower than the WHO threshold standard with a high proportion of patients being lost to the follow up. The co-infection of tuberculosis and HIV resulted in undesirable treatment outcomes. Strengthening TB surveillance and control is recommended.

Multidrug-resistant/rifampicin-resistant tuberculosis is a major obstacle to successful tuberculosis control. The recommendation by the WHO to use bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaL(M)) for 6 months, based on results of two trials with high efficacy and low toxicity, has revolutionized treatment options. In this study, representatives of the Tuberculosis Network European Trials group in 44 of 54 countries of the WHO Europe region documented the availability of the medicines and drug susceptibility testing (DST) of the BPaL(M) regimen through a structured questionnaire between September and November 2023. In total, 24 of 44 (54.5%), 42 of 44 (95.5%), 43 of 44 (97.7%), and 43 of 44 (97.7%) countries had access to pretomanid, bedaquiline, linezolid, and moxifloxacin, respectively. Overall, 23 of 44 (52.3%) countries had access to all the drugs composing the BPaL(M) regimen. In total, 21 of 44 (47.7%), 37 of 44 (84.1%), 40 of 44 (90.9%), and 41 of 44 (93.2%) countries had access to DST for pretomanid, bedaquiline, linezolid, and moxifloxacin, respectively. Overall, DST was available for all medicines composing the BPaL(M) regimen in 21 of 44 (47.7%) countries, including countries where pretomanid DST was available at specialized laboratories. The availability of DST for the drugs the countries had access to, varied from 87.5% to 95.3% (pretomanid 21 of 24 (87.5%), bedaquiline 37 of 42 (88.1%), linezolid 40 of 43 (93.1%) and moxifloxacin 41 of 43 (95.3%)). In only about half of the countries participating in the survey, clinicians had access to all the BPaL(M) regimen drugs. A complete DST for the BPaL(M) medicines was possible in less than half of the countries, because of the low accessibility of DST for pretomanid. Equal access to new regimens is urgently needed in Europe and a rapid scale up of DST, especially for pretomanid, is important to prevent unnoticed spread of drug resistance. [ABSTRACT FROM AUTHOR]

Background: The paper presents the salient features of a comprehensive treatment package for drug resistant tuberculosis (DR-TB), its adaptation and implementation in two indoor care hospital settings in Pakistan, and lessons learned from this implementation. Methods: A pilot study was undertaken on a group of 100 patients at two Programmatic Management of Drug-Resistant TB (PMDT) sites. Fifty patients each were selected from the Samli Sanatorium Murree and the Lady Reading Hospital, Peshawar by the National Tuberculosis Control authorities, and delivered a comprehensive package of services, including psychosocial and food support. Data were collected using standard TB tools and surveillance indicators. The results were compared between intervention and a historical cohort of DR-TB patients. Results: Among the total 100 patients, the treatment success rate was 88%, the failure rate was 4%, while there were 7% deaths. A patient was transferred out while none were lost to follow-up, indicating much improvement over the historical cohort. Patients ranked the economic support, free medicines and nutritional support as most helpful, while majority of providers found the intervention sustainable. Conclusion: A comprehensive package including the psychosocial support can be crucial in enhancing DR-TB outcomes. Regular interaction with patients and improved nutrition leads to improved treatment adherence, while capacity building of psychologists and home visits can further benefit the DR-TB patients leading to their cure. [ABSTRACT FROM AUTHOR]

Multidrug-resistant tuberculosis (MDR-TB) is currently an important public health problem in the world. Treatment of MDR-TB patients takes a long time, 20-24 months in standard regimen or 9-11 months in shorter regimen. Long treatment duration and drug toxicities which higher than drug-sensitive TB can cause drop out of treatment. Aisyiyah is a community social organization which provide assistance to TB patients in order to complete the treatment within specified time period. This study aimed to compare the outcome of DR-TB patients assisted by Aisyiyah and those who did not. A retrospective study was conducted Dr. Soetomo General Academic Hospital, Surabaya, Indonesia. Data was taken from DR-TB patients medical record since October 2014 until December 2017. There were 434 MDR-TB patients in the period of October 2014 to December 2017, with 75 patients (17.28%) received assistance from Aisyiyah. The average age was 44.38 ± 12.28 years old. Comparison between those who were assisted and not, from the male sex (49.3% vs 60.2%), women (50.7% vs 39.8%); based on resistance pattern: (5.3% vs 10.3%) from MDR TB, (85.3% vs 75.5%) from RR, (2.7% vs 8.1%) from XDR; Outcome obtained: Cure (1.6% vs 15.0%; p=0,031), Treatment completion (0.0% vs 0.5%; p=0,517), Default (2.8% vs 28.3%; p=0,002); Failed (0.2% vs 1.6%; p=0,718); Death (1.6% vs 7.9%; p=0,965). There were significant correlations between cure and default outcome in DR-TB patients accompanied by Aisyiyah compared to those not accompanied.

Abstract Background Ukraine has a high burden of drug-resistant tuberculosis (DR-TB). Mental health problems, including alcohol use disorder, are common co-morbidities. One in five DR-TB patients has human immunodeficiency virus (HIV). As part of health reform, the country is moving from inpatient care to ambulatory primary care for tuberculosis (TB). In Zhytomyr oblast, Médecins Sans Frontières (MSF) is supporting care for DR-TB patients on all-oral short DR-TB regimens. This study describes the preparedness of ambulatory care facilities in Zhytomyr oblast, Ukraine, to provide good quality ambulatory care. Methods This is a retrospective analysis of routinely collected programme data. Before discharge of every patient from the hospital, MSF teams assess services available at outpatient facilities using a standardised questionnaire. The assessment evaluates access, human resources, availability of medicines, infection control measures, laboratory and diagnostic services, and psychosocial support. Results We visited 68 outpatient facilities in 22 districts between June 2018 and September 2019. Twenty-seven health posts, 24 TB-units, 13 ambulatories, two family doctors and one polyclinic, serving 30% of DR-TB patients in the oblast by September 2019, were included. All facilities provided directly observed treatment, but only seven (10%) provided weekend-services. All facilities had at least one medical staff member, but TB-training was insufficient and mostly limited to TB-doctors. TB-treatment and adequate storage space were available in all facilities, but only five (8%) had ancillary medicines. HIV-positive patients had to visit a separate facility to access HIV-care. Personal protective equipment was unavailable in 32 (55%) facilities. Basic laboratory services were available in TB-units, but only four (17%) performed audiometry. Only ten (42%) TB-units had psychosocial support available, and nine (38%) offered psychiatric support. Conclusion Outpatient facilities in Zhytomyr oblast are not yet prepared to provide comprehensive care for DR-TB patients. Capacity of all facilities needs strengthening with trainings, infection control measures and infrastructure. Integration of psychosocial services, treatment of co-morbidities and adverse events at the same facility are essential for successful decentralisation. The health reform is an opportunity to establish quality, patient-centred care.

Coronavirus disease (COVID-19) pandemic determined a 10 years-set back in tuberculosis (TB) control programs. Recent advances in available therapies may help recover the time lost. While Linezolid (LZD) and Bedaquiline (BDQ), previously Group D second line drugs (SLDs) for TB, have been relocated to Group A, other drugs are currently being studied in regimens for drug resistant TB (DR-TB). Among these, Pretomanid (PA), a recently introduced antimycobacterial drug derived from nitroimidazole with both solid bactericidal and bacteriostatic effect, and with an excellent effectiveness and tolerability profile, is in the spotlight. Following promising data obtained from recently published and ongoing randomized controlled trials (RCTs), the World Health Organization (WHO) determined to include PA in its guidelines for the treatment of rifampicin-resistant (RR), multi drug resistant (MDR) and pre-extensively drug resistant TB (pre-XDR-TB) with BDQ, LZD and Moxifloxacine (MFX) in a 6-month regimen. Although further studies on the subject are needed, PA may also represent a treatment option for drug-susceptible TB (DS-TB), latent TB infection (LTBI) and non tuberculous mycobacteria (NTM). This narrative review aims to examine current implementation options and future possibilities for PA in the never-ending fight against TB.

Background: Drug-resistant tuberculosis (DR-TB) has become a serious cause of concern both on a global scale and in South Africa. It is associated with a lower successful treatment rate, thus creating a hurdle in achieving good treatment outcomes for patients. Aim: The aim of this study was to compare the efficacy of the drug kanamycin, an injectable aminoglycoside, to bedaquiline, a newer oral drug used to treat DR-TB. Methods: PubMed and Google Scholar, both of which are online databases, were extensively searched using the necessary keywords so that studies that were relevant to the scoping review were retrieved. A data-charting list was developed to extract the needed data for this scoping review. Results: The main findings of the scoping review showed that bedaquiline was highly efficacious in the treatment of DR-TB, and that it was a valuable addition in the treatment of DR-TB. The findings of the study also showed that kanamycin does not have good efficacy against DR-TB. and its use extends the treatment of DR˗TB. Conclusion: It stands to reason that bedaquiline replaces kanamycin in the DR-TB drug regimen as it was shown to be more efficacious and patients experienced better treatment outcomes in a shorter period of time. There were also fewer adverse effects associated with bedaquiline as compared to kanamycin. Contribution: Bedaquiline-based DR-TB therapy is more efficacious than aminoglycoside-based regimens which include kanamycin.

Abstract Background Currently available injectable agents are inadequate to address the high drug-resistant tuberculosis (DR-TB) burden in China. Regimens including the oral agent bedaquiline have been shown to be efficacious and safe, leading to its incorporation into multiple national TB treatment programs. This analysis evaluated the impact of increased adoption of bedaquiline-containing regimens on the DR-TB burden in China. Methods A state-transition model was developed that permits movement and interaction between susceptible, latent, and active TB disease states, while distinguishing between drug-sensitive (DS) and DR-TB. Model inputs were obtained from the published literature or derived such that model metrics approximated those published by the WHO. Expected improvements in infrastructure were built into the model to forecast the epidemiology of DR-TB in China through 2040 in the absence of bedaquiline (baseline forecast). The impact of higher utilization of bedaquiline-containing regimens (85% peak share) was then assessed in two scenarios that differed with regard to treatment success rates of the regimens: 61% (reflecting findings of clinical trials) and 80% (reflecting data from observational studies), versus the 44% success rate associated with standard-of-care treatment. Results In the baseline scenario, the model predicted increases in annual incidence of DR-TB by 6–8% during each five-year period between 2020 and 2040, with an increase of 30% over the entire study duration. Adoption of bedaquiline-based regimens limits the incidence increases to only 1–3% in each five-year period and to 8% over the study duration in the 61% success rate scenario. Incidence declines by 1–6% during each five-year period and by 12% over the study duration in the 80% success rate scenario. Similar effects on DR-TB prevalence (4–5% increase in baseline, 0–7% decline in scenario 1, and 4–19% decline in scenario 2) and mortality (5–7% increase in baseline, 0–16% decline in scenario 1, and 6–40% decline in scenario 2) were seen following bedaquiline adoption. Conclusions Incorporation of bedaquiline into DR-TB treatment regimens will significantly reduce the DR-TB burden in China, helping to counter the expected increase in burden in the absence of bedaquiline. The study will provide valuable information to public health policy planners.

Abstract Background Adverse events (AEs) are common during treatment of drug-resistant tuberculosis (DR-TB). Little is known about the health-related quality of life (HRQoL) of patients receiving treatment for DR-TB or the effect of AEs on HRQoL. Methods We conducted a cross-sectional study among adult patients with laboratory-confirmed rifampicin resistant tuberculosis (TB) on DR-TB treatment at a public-sector outpatient DR-TB clinic in Johannesburg, South Africa between 02/2015–01/2018. Data on HRQoL using the Medical Outcomes Short Form-36 (SF-36) questionnaire and self-reported AEs were collected by trained interviewers through face-to-face interviews. We report averages for the eight major domains and mental (MCS) and physical health (PCS) component summary scores, stratified by whether AEs were reported in the last four weeks. For comparative purposes, we enrolled two other patient groups and included data on a separate group of healthy adults. Results We enrolled 149 DR-TB patients (median age 36 years IQR 29–43, 55% male, 77.9% HIV-positive, 81% on ART, 61.8% on a standard long-course regimen and 44.3% on DR-TB treatment for less than 6 months). 58/149 (38.9%) patients reported a total of 122 AEs in the preceding 4 weeks, of these the most common were joint pain (n = 22), peripheral neuropathy (n = 16), hearing loss (n = 15), nausea and vomiting (n = 12) and dizziness or vertigo (n = 11). SF-36 domains and summary scores (MCS and PCS) were lower in those who reported an AE compared to those who did not, and both were lower than healthy adults. Compared to those who did not report an AE, patients who reported AEs were more likely to have a low MCS (aRR 2.24 95% CI 1.53–3.27) and PCS (aRR 1.52 95% CI 1.07–2.18) summary score. HRQoL was lower among those on DR-TB treatment for 6 months or less. Conclusion Results show that DR-TB had a substantial impact on patients’ quality of life, but that AEs during the early months on treatment may be responsible for reducing HRQoL even further. Our findings highlight the negative effects of injectable agents on HRQoL. Patients require an integrative patient-centered approach to deal with DR-TB and HIV and the potential overlapping toxicities which may be worsened by concurrent treatment.

Objectives: Indonesia is one of the top 20 countries with the highest prevalence of drug resistant tuberculosis (DRTB) worldwide with a percentage of new cases of 2.4% and retreatment of 13%. Bedaquiline (BDQ) is one of the drugs that used in the individual long regimen treating DR-TB. BDQ is also combined with levofloxacin (LFX) and/or clofazimine (CFZ) that can cause QTc interval prolongation. The aim was to study the differences in the use of BDQ regimens to the lengthening of the QTc interval and to study risk factors (diabetes, hypokalemia, sex, BMI, and age) in BDQ regimen. Methods: This study was an observational retrospective study with a total sampling method, which was conducted at Dr. Soetomo General Hospital Surabaya. Samples from this study were patients diagnosed with DR-TB at Dr. Soetomo General Hospital Surabaya in the period of January 2015–December 2019 who used BDQ regimen and met the inclusion criteria. The ECG data were analyzed from the mean of each group (BDQ regimen and risk factors), also analyzed using statistical analysis. Results: Data obtained from total sample in this study were 73 patients. The most widely used different regimens in this study were the combination of BDQ + LFX by 36 patients (49.3%), BDQ + LFX + CFZ by 16 patients (21.9%), BDQ by 11 patients (15.1%) and BDQ + CFZ 10 patients (13.7%). Out of 73 patients, 52 patients (71.2%) experienced lengthening of the QT interval and grade 1 of QTc interval prolongation occurred in most patients and also the onset was mostly one month after using BDQ regimen. The side effects of QTc interval prolongation from groups of combination and risk factors were no difference in each month (p>0.05). Conclusions: This study can be concluded that there were no differences in the QTc prolongation between the groups of BDQ regimen (BDQ, BDQ + LFX, BDQ + CFZ and BDQ + LFX + CFZ) and the groups of risk factors. [ABSTRACT FROM AUTHOR]

Regimens for the treatment of rifampicin-resistant tuberculosis currently rely on the use of QT-prolonging agents. Using data from the randomized controlled trial, TB-PRACTECAL, we investigated differences in QTcF among participants in the three interventional arms: BPaL (bedaquiline, pretomanid, and linezolid), BPaLC (BPaL with clofazimine), and BPaLM (BPaL with moxifloxacin). Additionally, we assessed whether age, body mass index, and country were causally associated with QTcF prolongation. The trial included participants from South Africa, Uzbekistan, and Belarus. A post hoc analysis of electrocardiogram data was undertaken. Random effects regression was used to model QTcF longitudinally over 24 weeks and causal frameworks guided the analysis of non-randomized independent variables. 328 participants were included in BPaL-based arms. The longitudinal analysis of investigational arms showed an initial QTcF steep increase in the first week. QTcF trajectories between weeks 2 and 24 differed slightly by regimen, with highest mean peak for BPaLC (QTcF 446.5 ms). Overall, there were 397 QTcF >450 ms (of 3,744) and only one QTcF >500 ms. The odds of QTcF >450 ms among participants in any investigational arm, was 8.33 times higher in Uzbekistan compared to Belarus (95% confidence interval: 3.25-21.33). No effect on QTcF prolongation was found for baseline age or body mass index (BMI). Clinically significant QTc prolongation was rare in this cohort of closely monitored participants. Across BPaL-based regimens, BPaLC showed a slightly longer and sustained effect on QTcF prolongation, but the differences (both in magnitude of change and trajectory over time) were clinically unimportant. The disparity in the risk of QTc prolongation across countries would be an important factor to further investigate when evaluating monitoring strategies., Clinical Trials: This study is registered with ClinicalTrials.gov as NCT02589782., Competing Interests: The authors declare no conflict of interest.

Background: Drug-resistant tuberculosis (DR-TB) has become a serious cause of concern both on a global scale and in South Africa. It is associated with a lower successful treatment rate, thus creating a hurdle in achieving good treatment outcomes for patients. Aim: The aim of this study was to compare the efficacy of the drug kanamycin, an injectable aminoglycoside, to bedaquiline, a newer oral drug used to treat DR-TB. Methods: PubMed and Google Scholar, both of which are online databases, were extensively searched using the necessary keywords so that studies that were relevant to the scoping review were retrieved. A data-charting list was developed to extract the needed data for this scoping review. Results: The main findings of the scoping review showed that bedaquiline was highly efficacious in the treatment of DR-TB, and that it was a valuable addition in the treatment of DR-TB. The findings of the study also showed that kanamycin does not have good efficacy against DR-TB. and its use extends the treatment of DR-TB. Conclusion: It stands to reason that bedaquiline replaces kanamycin in the DR-TB drug regimen as it was shown to be more efficacious and patients experienced better treatment outcomes in a shorter period of time. There were also fewer adverse effects associated with bedaquiline as compared to kanamycin. Contribution: Bedaquiline-based DR-TB therapy is more efficacious than aminoglycoside-based regimens which include kanamycin. [ABSTRACT FROM AUTHOR]

Multidrug-resistant tuberculosis (MDR-TB) is currently an important public health problem in the world. Treatment of MDR-TB patients takes a long time, 20-24 months in standard regimen or 9-11 months in shorter regimen. Long treatment duration and drug toxicities which higher than drug-sensitive TB can cause drop out of treatment. Aisyiyah is a community social organization which provide assistance to TB patients in order to complete the treatment within specified time period. This study aimed to compare the outcome of DR-TB patients assisted by Aisyiyah and those who did not. A retrospective study was conducted Dr. Soetomo General Academic Hospital, Surabaya, Indonesia. Data was taken from DR-TB patients medical record since October 2014 until December 2017. There were 434 MDR-TB patients in the period of October 2014 to December 2017, with 75 patients (17.28%) received assistance from Aisyiyah. The average age was 44.38 ± 12.28 years old. Comparison between those who were assisted and not, from the male sex (49.3% vs 60.2%), women (50.7% vs 39.8%); based on resistance pattern: (5.3% vs 10.3%) from MDR TB, (85.3% vs 75.5%) from RR, (2.7% vs 8.1%) from XDR; Outcome obtained: Cure (1.6% vs 15.0%; p=0,031), Treatment completion (0.0% vs 0.5%; p=0,517), Default (2.8% vs 28.3%; p=0,002); Failed (0.2% vs 1.6%; p=0,718); Death (1.6% vs 7.9%; p=0,965). There were significant correlations between cure and default outcome in DR-TB patients accompanied by Aisyiyah compared to those not accompanied. [ABSTRACT FROM AUTHOR]

Background: Currently available injectable agents are inadequate to address the high drug-resistant tuberculosis (DR-TB) burden in China. Regimens including the oral agent bedaquiline have been shown to be efficacious and safe, leading to its incorporation into multiple national TB treatment programs. This analysis evaluated the impact of increased adoption of bedaquiline-containing regimens on the DR-TB burden in China.Methods: A state-transition model was developed that permits movement and interaction between susceptible, latent, and active TB disease states, while distinguishing between drug-sensitive (DS) and DR-TB. Model inputs were obtained from the published literature or derived such that model metrics approximated those published by the WHO. Expected improvements in infrastructure were built into the model to forecast the epidemiology of DR-TB in China through 2040 in the absence of bedaquiline (baseline forecast). The impact of higher utilization of bedaquiline-containing regimens (85% peak share) was then assessed in two scenarios that differed with regard to treatment success rates of the regimens: 61% (reflecting findings of clinical trials) and 80% (reflecting data from observational studies), versus the 44% success rate associated with standard-of-care treatment.Results: In the baseline scenario, the model predicted increases in annual incidence of DR-TB by 6-8% during each five-year period between 2020 and 2040, with an increase of 30% over the entire study duration. Adoption of bedaquiline-based regimens limits the incidence increases to only 1-3% in each five-year period and to 8% over the study duration in the 61% success rate scenario. Incidence declines by 1-6% during each five-year period and by 12% over the study duration in the 80% success rate scenario. Similar effects on DR-TB prevalence (4-5% increase in baseline, 0-7% decline in scenario 1, and 4-19% decline in scenario 2) and mortality (5-7% increase in baseline, 0-16% decline in scenario 1, and 6-40% decline in scenario 2) were seen following bedaquiline adoption.Conclusions: Incorporation of bedaquiline into DR-TB treatment regimens will significantly reduce the DR-TB burden in China, helping to counter the expected increase in burden in the absence of bedaquiline. The study will provide valuable information to public health policy planners. [ABSTRACT FROM AUTHOR]

A rapid diagnosis of drug-resistant tuberculosis (TB) is critical for early initiation of effective therapy. Molecular testing with line probe assays (MTBDRplus and MTBDRsl) on culture isolates has been available for some time and significantly reduces the time to diagnosis of drug resistance. However, routine use of this test directly on sputum is less common. As part of enrollment screening procedures for tuberculosis clinical trials conducted in Hanoi, Vietnam, we evaluated the feasibility and performance of line probe assay (LPA) testing directly on sputum samples from 315 participants with no prior history of TB treatment. Test performance characteristics for the detection of rifampin (RIF) and isoniazid (INH) drug resistance as compared to culture-based drug susceptibility testing (DST) reference standard were calculated. LPA demonstrated high sensitivity and specificity for the diagnosis of drug resistance. Scaling up molecular testing on sputum as part of time-sensitive clinical trial screening procedures in high TB burden settings is feasible and will reduce both time to initiation of appropriate therapy and the risk of late exclusions due to microbiologic ineligibility.

Background: PMDT was launched in 2007 in our country but drug resistant TB remains to be a public health problem. Effective surveillance is the backbone for success of any programme and true stands for PMDT. Aim & Objectives: To identify the strengths and constraints of the surveillance evaluation system. Material & Methods: A cross sectional study was conducted in January 2015 at DR-TB Centre of NITRD, New Delhi which caters to a population of 29 lacs. PMDT surveillance system was evaluated using attributes like simplicity, data quality, acceptability, positive predictive value, representativeness and timeliness defined by CDC, USA guidelines. Relevant information was collected using data abstraction form and interview with stakeholders. Data was analysed using EpiInfo 07 version. Results: Nodal officer and District TB officer are responsible for surveillance system activities of PMDT at DR-TB centre and district level, respectively. All the reports (100%) were submitted on time and all the districts were reporting to DR-TB centre. 75% of TB-HIV coordinators found reporting formats to be simple but all the quarterly reports were found to be complete. Data quality was not found to be optimal. Conclusion: Private sector needs to be taken on board as they have no to minimal involvement in PMDT. For data quality improvement time to time training of medical officers and health workers should be organized. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a preventable, treatable, and curable disease. However, in 2020, 9∙9 million people were estimated to have developed tuberculosis, and 1.5 million people were estimated to have died from it. Whereas in India, 2.6 million were diagnosed with TB and 436,000 succumbed to TB in 2019. India (26%) is the major contributor to the global drop in TB cases. The COVID-19 pandemic has substantially reduced access to services for the diagnosis and treatment of TB, resulting in an increase in deaths and a reversal in global progress. [1] Presently, TB incidence is falling at a rate of 2% per year, obstructed mainly by the rearing pandemic of drug-resistant tuberculosis (DRTB). Particularly concerning is multi-drug resistant TB (MDRTB), defined as resistance towards isoniazid (INH) and rifampicin (RIF). [2] The World Health Organization (WHO) targeted to reduce worldwide TB incidence by 90% until 2035. (1) Early initiation of effective treatment based on susceptibility patterns of the Mycobacterium tuberculosis complex (MTBC) is considered key to successful TB control in countries with high DRTB incidence. Worldwide MDRTB treatment outcomes are poor, with cure rates less than 60% (2) due to the lack of comprehensive Drug Susceptibility Testing (DST) in most high MDRTB burden countries. This is leading to the inadequate anti-TB activity of the provided regimens (3-5), unlike regimens advised for DST assure optimal results. (6) In addition to resistances to the established regimens, the resistance to the newer DRTB drugs is increasing. On World TB Day 2022, Academy of Advanced Medical Education, Thyrocare Technologies Limited and HyastackAnalytics - IITB along with expert pulmonologist and renowned physicians from India convened for an advisory board meeting in Delhi on 20th March 2022 to discuss the role of Whole Genome Sequencing (WGS) in the diagnosis and management of TB. Objectives and specific topics relating to WGS in MDRTB were discussed, each expert shared their views, which led to a group discussion with a commitment to putting the patient first, and increasing their collective efforts, the organizations recognized that it is possible to make this goal a reality. The organizations involved in the discussion have declared their commitment to engaging in collaborative efforts to tackle DRTB detection efficiently. They advocate for strengthening access to WGS TB services, controlling and preventing TB, improving surveillance and drug resistance management, and investing in research and development. This Round Table serves as a framework to build on and ensure that the goal of ending TB is achievable with WGS services wherever needed. Post discussion, a uniform consensus was said to be arrived if more than 80% board members agreed to the statement. The present paper is the outcome of aspects presented and discussed in the advisory board meeting., Competing Interests: Conflicts of interest The authors have none to declare., (Copyright © 2023 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Background: Specific death due to DR-TB has significantly contributed to tuberculosis (TB) mortality and overall global deaths., Aim: This study examines the predictors of mortality among DR-TB patients in Kaduna State, Nigeria., Subject and Method: This was a retrospective longitudinal study of DR-TB mortality carried out among 370 DR-TB patients from the 23 LGAs in Kaduna State. It involves a retrospective review of the MDR-TB records of the patients over a period of 10 years (2012-2021). Demographic and clinical data of all DR-TB patients enrolled in Kaduna State, Nigeria, between April 1, 2012, and March 31, 2021, were used. Survival analysis was performed with SPSS version 25, using Kaplan-Meier and Cox proportional hazard regression modeling, at 5% significance level., Results: The majority of the patients, 255 (68.9%), were below the age of 40 years, while 53 (14.3%) of the patients died within the study period. Most deaths 26 (49.1%) were associated with HIV co-infection and the disease severity. Results for the Cox proportional model show that there was a significantly lower risk of death when a patient had MDR-TB compared to pre-XDR-TB (adjusted hazard ratio, AHR = 0.34, 95% CI = 0.16-0.72, P = 0.04). Both models show that age, sex, residence, or year of treatment had no significant association with survival or death., Conclusion: HIV co-infection and DRTB with progression to more resistant and difficult-to-treat strains contributed to higher deaths. There is a need for concerted efforts from all DR-TB stakeholders to control the disease., Competing Interests: None

Background: South Africa has high burdens of HIV, TB and drug-resistant TB (DR-TB, rifampicin-resistance). Treatment outcome data for HIV-infected versus uninfected patients is limited. We assessed the impact of HIV and other factors on DR-TB treatment success, time to culture conversion, loss-from-treatment and overall mortality after second-line treatment initiation. Methods: A retrospective cohort analysis was conducted for patients initiated on DR-TB treatment from 2008 to 2012, within a community-based, decentralised programme in Khayelitsha, South Africa. Results: Among 853 confirmed DR-TB patients initiating second-line treatment, 605 (70.9%) were HIV infected. HIV status did not impact on time to sputum culture conversion nor did it impact treatment success; 48.1% (259/539) and 45.9% (100/218), respectively (p=0.59). In a multivariate model, HIV was not associated with treatment success. Death during treatment was higher among HIV-infected patients, but overall mortality was not significantly higher. HIV-infected patients with CD4 <=100 cells/ml were significantly more likely to die after starting treatment. Conclusions: Response to DR-TB treatment did not differ with HIV infection in a programmatic setting with access to antiretroviral treatment (ART). Earlier ART initiation at a primary care level could reduce mortality among HIV-infected patients presenting with low CD4 counts. [ABSTRACT FROM AUTHOR]

Background: Surgery in DR-TB is a highly contested intervention. However, in suitable selected cases, it has a great role in improving outcomes of treatment as well as symptomatic improvement in the quality of life of the patient. Indications of surgery in this setting will be localized disease with high likelihood of persistent progression or sputum positivity despite adequate therapy. Recurrent hemoptysis, intolerance to drugs or absence of radiological and bacteriological improvement during initial 3–4 months of therapy becomes additional indications for surgical intervention. A review of 11 studies published in a period from 1993 to 2013 provides enough justification for the role of surgical intervention in pulmonary tuberculosis. Interventions: At the NITRD, in the last 20 years a total of 107 cases have been operated upon for DR-TB. Procedures done were 70 pneumonectomies, 20 lobectomies, 5 bilobectomies, 4 nonanatomical resections and 7 thoracoplasties. Results: Sputum negativity was achieved in 93 cases after surgery and 62 were declared cured after 4 years of follow up. 6 cases of DR TB were also operated upon in March 2013 in one MSF TB surgery mission and all of them are sputum negative till March 2015. Conclusions: In conclusion, surgical intervention should be offered and made available for greater number of DR-TB patients.