Operational research as a mechanism to improve treatment outcomes for drug-resistant TB in the WHO European Region.

In 2022, the WHO European Region accounted for 15.1% of all incident rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB) cases. Most occurred in 18 high-priority countries of eastern Europe and central Asia, many of which joined an initiative led by the WHO Regional Office for Europe. The aim was to introduce three, fully oral, 9-month modified shorter treatment regimens (mSTR) to treat RR/MDR-TB under operational research conditions. The three regimens were: 1) bedaquiline + linezolid + levofloxacin + clofazimine + cycloserine (BdqLzdLfxCfzCs); 2) BdqLzdLfxCfz + delamanid (Dlm) for children over 6 years of age and adults; and 3) DlmLzdLfxCfz for children under 6 years of age. The project aimed to enhance treatment success, facilitate mSTR implementation, promote quality of care and build research capacity, while also contributing to global knowledge on all-oral mSTR use. Between April 2020 and June 2022, >2,800 patients underwent mSTR treatment in the WHO European Region. This unique experience promoted further collaboration with national tuberculosis programmes, health authorities, experts and donors within and outside Europe, with a focus on implementing operational research and improving the quality of care in high TB burden countries of the region. In the hope of encouraging others to adopt this model, we have described the principles of the initiative, its strengths and weaknesses and next steps.

En 2022, la Région européenne de l'OMS a recensé 15,1% de l'ensemble des cas de TB résistante à la rifampicine/multirésistante aux médicaments (RR/MDR-TB). La majorité de ces cas ont eu lieu dans 18 pays hautement prioritaires d'Europe orientale et d'Asie centrale, parmi lesquels de nombreux ont adhéré à une initiative dirigée par le Bureau régional de l'OMS pour l'Europe. L'objectif était de mettre en place trois schémas thérapeutiques modifiés plus courts de 9 mois, entièrement oraux, (mSTR, pour l'anglais "fully oral, 9-month modified shorter treatment regimens ¼) pour le traitement de la RR/MDR-TB dans le cadre d'une recherche opérationnelle. Ces trois schémas étaient les suivants 1) bédaquiline + linézolide + lévofloxacine + clofazimine + cyclosérine (BdqLzdLfxCfzCs) ; 2) BdqLzdLfxCfz + delamanid (Dlm) pour les enfants de plus de 6 ans et les adultes ; et 3) DlmLzdLfxCfz pour les enfants de moins de 6 ans. Le projet visait à améliorer l'efficacité des traitements, à faciliter l'application des mSTR, à promouvoir la qualité des soins et à renforcer les capacités de recherche, tout en contribuant aux connaissances mondiales sur l'utilisation des mSTR par voie orale. Entre avril 2020 et juin 2022, plus de 2 800 patients ont reçu un traitement par mSTR dans la Région Européenne de l'OMS. Cette expérience unique a encouragé la continuation de la collaboration avec les programmes nationaux de lutte contre la TB, les autorités sanitaires, les experts et les donateurs tant en Europe qu'à l'étranger. L'accent est mis sur la mise en œuvre de la recherche opérationnelle et l'amélioration de la qualité des soins dans les pays de la région où la TB est fortement prévalente. Nous avons détaillé les principes de l'initiative, ses avantages et ses inconvénients, dans l'espoir d'inciter d'autres pays à suivre cet exemple, tout en exposant les étapes à venir.

Epidemiology and antimicrobial resistance of Mycobacterium spp. in the United Arab Emirates: a retrospective analysis of 12 years of national antimicrobial resistance surveillance data.

Introduction: The Eastern Mediterranean Regional Office (EMRO) region accounts for almost 8% of all global Mycobacterium tuberculosis (TB) cases, with TB incidence rates ranging from 1 per 100,000 per year in the United Arab Emirates (UAE) to 204 per 100,000 in Djibouti. The national surveillance data from the Middle East and North Africa (MENA) region on the epidemiology and antimicrobial resistance trends of TB, including MDR-TB remains scarce. Methods: A retrospective 12-year analysis of N = 8,086 non-duplicate diagnostic Mycobacterium tuberculosis complex (MTB complex) isolates from the UAE was conducted. Data were generated through routine patient care during the 2010-2021 years, collected by trained personnel and reported by participating surveillance sites to the UAE National Antimicrobial Resistance (AMR) Surveillance program. Data analysis was conducted with WHONET, a windows-based microbiology laboratory database management software developed by the World Health Organization Collaborating Center for Surveillance of Antimicrobial Resistance, Boston, United States (https://whonet.org/). Results: A total of 8,086 MTB-complex isolates were analyzed. MTB-complex was primarily isolated from respiratory samples (sputum 80.1%, broncho-alveolar lavage 4.6%, pleural fluid 4.1%). Inpatients accounted for 63.2%, including 1.3% from ICU. Nationality was known for 84.3% of patients, including 3.8% Emiratis. Of UAE non-nationals, 80.5% were from 110 countries, most of which were Asian countries. India accounted for 20.8%, Pakistan 13.6%, Philippines 12.7%, and Bangladesh 7.8%. Rifampicin-resistant MTB-complex isolates (RR-TB) were found in 2.8% of the isolates, resistance to isoniazid, streptomycin, pyrazinamide, and ethambutol, was 8.9, 6.9, 3.4 and 0.4%, respectively. A slightly increasing trend of resistance among MTB-complex was observed for rifampicin from 2.5% (2010) to 2.8% (2021). Conclusion: Infections due to MTB-complex are relatively uncommon in the United Arab Emirates compared to other countries in the MENA region. Most TB patients in the UAE are of Asian origin, mainly from countries with a high prevalence of TB. Resistance to first line anti-tuberculous drugs is generally low, however increasing trends for MDR-TB mainly rifampicin linked resistance is a major concern. MDR-TB was not associated with a higher mortality, admission to ICU, or increased length of hospitalization as compared to non-MDR-TB.

Coarse particulate air pollution and mortality in a multidrug-resistant tuberculosis cohort.

RATIONALE: The association between ambient coarse particulate matter (PM2.5-10) and mortality in multi-drug resistant tuberculosis (MDR-TB) patients has not yet been studied. The modifying effects of temperature and humidity on this association are completely unknown. OBJECTIVES: To evaluate the effects of long-term PM2.5-10 exposures, and their modifications by temperature and humidity on mortality among MDR-TB patients. METHODS: A Chinese cohort of 3469 MDR-TB patients was followed up from diagnosis until death, loss to follow-up, or the study's end, averaging 2567 days per patient. PM2.5-10 concentrations were derived from the difference between PM10 and PM2.5. Cox proportional hazard models estimated hazard ratios (HRs) per 3.74 µg/m3 (interquartile range, IQR) exposure to PM2.5-10 and all-cause mortality for the full cohort and individuals at distinct long-term and short-term temperature and humidity levels, adjusting for other air pollutants and potential covariates. Exposure-response relationships were quantified using smoothed splines. RESULTS: Hazard ratios of 1.733 (95% CI, 1.407, 2.135) and 1.427 (1.114, 1.827) were observed for mortality in association with PM2.5-10 exposures for the full cohort under both long-term and short-term exposures to temperature and humidity. Modifying effects by temperature and humidity were heterogenous across sexes, age, treatment history, and surrounding environment measured by greenness and nighttime light levels. Nonlinear exposure-response curves suggestes a cumulative risk of PM2.5-10-related mortality starting from a low exposure concentration around 15 µg/m3. CONCLUSION: Long-term exposure to PM2.5-10 poses significant harm among MDR-TB patients, with effects modified by temperature and humidity. Immediate surveillance of PM2.5-10 is crucial to mitigate the progression of MDR-TB severity, particularly due to co-exposures to air pollution and adverse weather conditions.

Silent epidemic of silicotuberculosis in India and emergence of multidrug-resistant tuberculosis?

India's projected silica-dust-exposed workers will be 52 million at the end of 2025. Elimination of tuberculosis is also targeted in India by 2025. Scientists in India have already pointed out that unless silicosis is controlled, the said elimination is difficult to achieve. This study evidences an increasing incidence of tuberculosis and multidrug resistant tuberculosis (MDR-TB) with five deaths due to treatment failure among the silica dust-exposed workers compared to their unexposed counterparts. It was also observed that both tuberculosis as well as MDR-TB were directly proportional to the dose and/or duration of silica dust exposure. This means the incidence of MDR-TB is lowest in the unexposed group, moderate in the radiologically negative but silica dust exposed group (subradiological silicosis due to moderate exposure), and highest in the radiologically confirmed silicotic workers (maximally exposed group. Since India has a huge burden of silicosis, they are vulnerable to tuberculosis including multidrug-resistant tuberculosis resulting in the emergence of MDR-TB among the silica dust-exposed workers. This will also lead to a silent epidemic of silicotuberculosis in India shortly. Therefore, it would be important to have tools to quickly detect silicosis cases at an early stage to identify a vulnerable population and adopt an effective intervention measure.

Advancements in Artificial Intelligence for the Diagnosis of Multidrug Resistance and Extensively Drug-Resistant Tuberculosis: A Comprehensive Review.

Tuberculosis (TB) remains a significant global health concern, particularly with the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). Traditional methods for diagnosing drug resistance in TB are time-consuming and often lack accuracy, leading to delays in appropriate treatment initiation and exacerbating the spread of drug-resistant strains. In recent years, artificial intelligence (AI) techniques have shown promise in revolutionizing TB diagnosis, offering rapid and accurate identification of drug-resistant strains. This comprehensive review explores the latest advancements in AI applications for the diagnosis of MDR-TB and XDR-TB. We discuss the various AI algorithms and methodologies employed, including machine learning, deep learning, and ensemble techniques, and their comparative performances in TB diagnosis. Furthermore, we examine the integration of AI with novel diagnostic modalities such as whole-genome sequencing, molecular assays, and radiological imaging, enhancing the accuracy and efficiency of TB diagnosis. Challenges and limitations surrounding the implementation of AI in TB diagnosis, such as data availability, algorithm interpretability, and regulatory considerations, are also addressed. Finally, we highlight future directions and opportunities for the integration of AI into routine clinical practice for combating drug-resistant TB, ultimately contributing to improved patient outcomes and enhanced global TB control efforts.

Distribution of tuberculosis in migrant children and young people in Europe: a retrospective database analysis of European data.

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

New synergistic benzoquinone scaffolds as inhibitors of mycobacterial cytochrome bc1 complex to treat multi-drug resistant tuberculosis.

Through a comprehensive molecular docking study, a unique series of naphthoquinones clubbed azetidinone scaffolds was arrived with promising binding affinity to Mycobacterial Cytbc1 complex, a drug target chosen to kill multi-drug resistant Mycobacterium tuberculosis (MDR-Mtb). Five compounds from series-2, 2a, 2c, 2g, 2h, and 2j, showcased significant in vitro anti-tubercular activities against Mtb H37Rv and MDR clinical isolates. Further, synergistic studies of these compounds in combination with INH and RIF revealed a potent bactericidal effect of compound 2a at concentration of 0.39 µg/mL, and remaining (2c, 2g, 2h, and 2j) at 0.78 µg/mL. Exploration into the mechanism study through chemo-stress assay and proteome profiling uncovered the down-regulation of key proteins of electron-transport chain and Cytbc1 inhibition pathway. Metabolomics corroborated these proteome findings, and heightened further understanding of the underlying mechanism. Notably, in vitro and in vivo animal toxicity studies demonstrated minimal toxicity, thus underscoring the potential of these compounds as promising anti-TB agents in combination with RIF and INH. These active compounds adhered to Lipinski's Rule of Five, indicating the suitability of these compounds for drug development. Particular significance of molecules NQ02, 2a, and 2h, which have been patented (Published 202141033473).

Tuberculosis in Poland in 2021. / Gruzlica w Polsce w 2021 r.

AIM OF THE STUDY: To evaluate the main features of epidemiology of tuberculosis (TB) in 2021 in Poland and to compare with the situation in the European Union and European Economic Area (EU/EEA) countries. MATERIAL AND METHODS: Analysis of case-based data on TB patients from National TB Register, data on anti-TB drug susceptibility in cases notified in 2021, data from Statistics Poland on deaths from tuberculosis in 2020, data from National Institute of Public Health NIH - National Research Institute (NIPH NIH - NRI) on HIV-positive subjects for whom TB was an AIDS-defining disease, data from the report "European Centre for Disease Prevention and Control, WHO Regional Office for Europe. Tuberculosis surveillance and monitoring in Europe 2022 - 2021 data. Copenhagen: WHO Regional Office for Europe and Stockholm: European Centre for Disease Prevention and Control; 2022." RESULTS: In 2021, 3704 TB cases were reported in Poland. The incidence rate was 9.7 cases per 100,000 with large variability between voivodeships from 5.4 to 12.6 per 100,000. A decrease in the incidence with respect to 2020 was found in 8 voivodeships, the most significant in lubuskie voivodship (42.6%). The number of all pulmonary tuberculosis cases was 3,553 i.e. 9.3 per 100,000. Pulmonary cases represented 95.9% of all TB cases. In 2021, 151 extrapulmonary TB cases were notified (4.1% of all TB cases). Pulmonary tuberculosis was bacteriologically confirmed in 2,970 cases (83.6% of all pulmonary TB cases, the incidence rate 7.8 per 100,000). The number of smear-positive pulmonary TB cases was 2,085 i.e. 5.5 per 100,000 (58.7% of all pulmonary TB cases). In 2021, there were 54 cases (25 of foreign origin) with multidrug resistant TB (MDR-TB) representing 1.9% of cases with known drug sensitivity. The incidence rates of tuberculosis were growing along with the age group from 0.6 per 100,000 among children (0-14 years) to 15.8 per 100,000 among subjects in the age group 45-64 years, the incidence rate in the age group ≥65 years was 11.7 per 100,000. There were 37 cases in children up to 14 years of age (1.0% of the total) and 51 cases in adolescents between 15 and 19 years of age - rates 0.6 and 2.8 per 100,000 respectively. In 2021, there were 2,690 cases of tuberculosis in men and 1,014 in women. The TB incidence in men - 14.6 per 100,000 was almost 3.0 times higher than among women - 5.1. The biggest difference in the TB incidence between the two sex groups occurred in persons aged 55-59 years, 30.5 vs. 6.6 and in age group 60 to 64 years, 26.0 vs. 5.7. In 2021, there were 132 patients of foreign origin among all cases of tuberculosis in Poland (3.6%). In 2020, TB was the cause of death for 474 people (mortality rate - 1.2 per 100,000). CONCLUSIONS: The incidence of tuberculosis in Poland in 2021 was 10.2% higher than in 2020. The percentage of tuberculosis cases with bacteriological confirmation was 82.6%, higher than the average in EU/EEA countries (72.0%). The percentage of MDR-TB cases was lower than the average in EU/EEA countries (1.9% vs. 3.8%). The highest incidence rates are found in Poland in the older age groups (in EU/EEA countries in people aged 25 to 44). The percentage of children up to 14 years of age among the total number of TB patients was 1.0%, the average in the EU/EEA countries was 3.5%. The incidence of tuberculosis in men was nearly three times higher than in women in Poland. The impact of migration on the epidemiological situation of tuberculosis in Poland in 2021 was smaller than in the EU/EEA countries (in Poland, the percentage of foreigners among all TB patients was 3.6 vs. 33.8% in the EU/EEA).

Effectiveness, cost, and safety of four regimens recommended by WHO for RR/MDR-TB treatment: a cohort study in Eastern China.

BACKGROUND: To compare the effectiveness, cost, and safety of four regimens recommended by the World Health Organization (WHO) for rifampicin resistance/multidrug-resistance tuberculosis (RR/MDR-TB) Treatment in Eastern China. METHODS: We performed a cohort study among patients with RR/MDR between 2020 and 2022 in Jiangsu Province. The treatment success rate, cost, and drug adverse reaction rate were compared. RESULTS: Between 2020 and 2022, 253 RR/MDR-TB patients were enrolled in the study. 37 (14.62%), 76 (30.04%), 74 (29.25%), and 66 (26.09%) patients had the short-term regimens, the new long-term oral regimens, the new long-term injectable regimens, and the traditional long-term regimens, respectively. The treatment success rate was the highest among patients treated with the short-term regimen (75.68%) and was the lowest among patients treated with the traditional long-term regimens (60.61%). The estimated mean cost per favorable outcome was 142.61 thousand Chinese Yuan (CNY), and the short-term regimens showed the lowest cost in the four regimes (88.51 thousand CNY vs. 174.24 thousand CNY, 144.00 thousand CNY, and 134.98 thousand CNY). Incremental cost-effectiveness ratios of the short-term regimens, the new long-term oral regimen, and the new long-term injectable regimens were -3083.04, 6040.09, and 819.68 CNY compared to the traditional long-term regimens. CONCLUSIONS: For RR/MDR-TB patients in China who meet the criteria for short-term regimens, the short-term regimens were proven to be the most cost-effective of the four regimens recommended by WHO. For RR/MDR-TB patients in China who don't meet the criteria for short-term regimens, the new long-term injectable regimens are more cost-effective than the remaining two regimens.

This is the first study to evaluate the effectiveness, cost, and safety of four regimens recommended by the WHO for RR/MDR-TB treatment in China.For RR/MDR-TB patients in China who meet the criteria for the short-term regimens, the short-term regimens were proven to be the most cost-effective of the four regimens recommended by WHO.

Multidrug-resistant tuberculosis.

One of predominant contributors to global mortality is tuberculosis (TB), an infection caused by Mycobacterium tuberculosis (MTB). Inappropriate and ineffectual treatment can lead to the development of drug-resistant TB. One of the most common forms of drug-resistant TB is multidrug-resistant tuberculosis (MDR-TB), caused by mutations in the rpoB and katG genes that lead to resistance to anti-TB drugs, rifampicin (RIF) and isoniazid (INH), respectively. Although culturing remains the gold standard, it is not rapid thereby delaying potential treatment and potentially increasing the incidence of MDR-TB. In contrast, molecular techniques provide a highly sensitive and specific alternative. This review discusses the classification of biomarkers used to detect MDR-TB, some of the commonly used anti-TB drugs, and DNA mutations in MTB that lead to anti-TB resistance. The objective of this review is to increase awareness of the need for rapid and precise detection of MDR-TB cases to decrease morbidity and mortality of this infectious disease worldwide.

Confronting Tuberculosis: A Synthetic Quinoline-Isonicotinic Acid Hydrazide Hybrid Compound as a Potent Lead Molecule Against Mycobacterium tuberculosis.

The current tuberculosis (TB) treatment is challenged by a complex first-line treatment for drug-sensitive (DS) TB. Additionally, the prevalence of multidrug (MDR)- and extensively drug (XDR)-resistant TB necessitates the search for new drug prototypes. We synthesized and screened 30 hybrid compounds containing aminopyridine and 2-chloro-3-formyl quinoline to arrive at a compound with potent antimycobacterial activity, UH-NIP-16. Subsequently, antimycobacterial activity against DS and MDR Mycobacterium tuberculosis (M.tb) strains were performed. It demonstrated an MIC50 value of 1.86 ± 0.21 µM for laboratory pathogenic M.tb strain H37Rv and 3.045 ± 0.813 µM for a clinical M.tb strain CDC1551. UH-NIP-16 also decreased the MIC50 values of streptomycin, isoniazid, ethambutol, and bedaquiline to about 45, 55, 68, and 76%, respectively, when used in combination, potentiating their activities. The molecule was active against a clinical MDR M.tb strain. Cytotoxicity on PBMCs from healthy donors and on human cell lines was found to be negligible. Further, blind docking of UH-NIP-16 using Auto Dock Vina and MGL tools onto diverse M.tb proteins showed high binding affinities with multiple M.tb proteins, the top five targets being metabolically critical proteins CelA1, DevS, MmaA4, lysine acetyltransferase, and immunity factor for tuberculosis necrotizing toxin. These bindings were confirmed by fluorescence spectroscopy using a representative protein, MmaA4. Envisaging that a pathogen will have a lower probability of developing resistance to a hybrid molecule with multiple targets, we propose that UH-NIP-16 can be further developed as a lead molecule with the bacteriostatic potential against M.tb, both alone and in combination with first-line drugs.

Factors Associated with Non-Adherence to Treatment Among Migrants with MDR-TB in Wuhan, China: A Cross-Sectional Study.

Background: Multidrug resistant tuberculosis (MDR-TB) has attracted increasing attention in achieving the global goal of tuberculosis (TB) control. China has the second largest TB burden worldwide and has been experiencing large-scale domestic migration. This study aims to explore the effect of migrants on non-adherence to MDR-TB treatment. Materials and Methods: A cross-sectional study was carried out in Wuhan, China. The exposure cases were migrants who were not locally registered in the residence registration system. The control cases were local residents. Non-adherence cases were patients who were lost follow-up or refused treatment. Chi-square and t-test were used to compare variables between migrants and local residents. Logistic regression models using enter method were used to determine the relationship between migration and non-adherence to treatment. Moderation and medication effects on the association between migrant status and non-adherence were also explored. Results: We studied 73 migrants and 219 local residents. The migrants, who did not to adhere to treatment (55, 75.3%), was far higher than that of local residents (89, 40.6%). Migrants with MDR-TB had 10.38-times higher difficulty in adhering to treatment (adjusted OR = 10.38, 95% CI 4.62-25.28) than local residents. This additional likelihood was moderated by age and treatment registration group. Migration had an indirect association with non-adherence to treatment via social medial insurance (adjusted OR = 1.05, 95% CI 1.01-1.13). Conclusion: There a significant increased likelihood of non-adherence to treatment among migrants with MDR-TB, highlighting the importance of improving treatment adherence in this population. Migration prevented migrants from gaining access to social medical insurance and indirectly reduced their likelihood of adherence to treatment.

Frequency, management and impact of adverse events on treatment outcomes in patients with multidrug resistant tuberculosis in Balochistan, Pakistan.

Background: Early detection, monitoring, and managing adverse events (AEs) are crucial in optimising treatment for multidrug-resistant tuberculosis (MDR-TB) patients. Objectives: To investigate the incidence, factors, management, and impact of AEs on treatment outcomes in MDR-TB patients. Methods: This study reviewed the medical records of 275 MDR-TB patients at Fatimah Jinnah Institute of Chest Diseases in Quetta, Pakistan. Patient information was collected using a designed data collection form. Mann-Whitney U and Kruskal-Wallis tests examined the difference in AEs occurrences based on patients' characteristics. Multiple binary logistic regression identified factors associated with unsuccessful outcomes, with statistical significance set at a p-value < 0.05. Results: Almost all patients (99.6%) experienced at-least one AE (median = 4/patient, interquartile range:3-6). The most common were GI disturbance (95.3%), arthralgia (80.4%), body pain and headache (61.8%), ototoxicity (61.4%), psychiatric disturbance (44%), hypokalaemia (40.4%), dermatological reactions (26.2%) and hypothyroidism (21.5%). AEs led to treatment modification in 7.3% patients. Educated patients, those with a history of TB treatment, previous use and resistance to any second-line drug had significantly higher number of AEs. A total of 64.0% were declared cured, 3.6% completed treatment, 19.6% died and 12.7.9% were lost to follow-up. Patients' age of 41-60(OR = 9.225) and >60 years(OR = 23.481), baseline body weight of 31-60 kg(OR = 0.180), urban residence(OR = 0.296), and experiencing ototoxicity (OR = 0.258) and hypothyroidism (OR = 0.136) were significantly associated with unsuccessful treatment outcomes. Conclusion: AEs were highly prevalent but did not negatively impact treatment outcomes. Patients at higher risk of developing AEs and unsuccessful outcomes should receive special attention for its early management.

Exploring health care providers' engagement in prevention and management of multidrug resistant Tuberculosis and its factors in Hadiya Zone health care facilities: qualitative study.

BACKGROUND: Engagement of healthcare providers is one of the World Health Organization strategies devised for prevention and provision of patient centered care for multidrug resistant tuberculosis. The need for current research question rose because of the gaps in evidence on health professional's engagement and its factors in multidrug resistant tuberculosis service delivery as per the protocol in the prevention and management of multidrug resistant tuberculosis. PURPOSE: The purpose of this study was to explore the level of health care providers' engagement in multidrug resistant tuberculosis prevention and management and influencing factors in Hadiya Zone health facilities, Southern Ethiopia. METHODS: Descriptive phenomenological qualitative study design was employed between 02 May and 09 May, 2019. We conducted a key informant interview and focus group discussions using purposely selected healthcare experts working as directly observed treatment short course providers in multidrug resistant tuberculosis treatment initiation centers, program managers, and focal persons. Verbatim transcripts were translated to English and exported to open code 4.02 for line-by-line coding and categorization of meanings into same emergent themes. Thematic analysis was conducted based on predefined themes for multidrug resistant tuberculosis prevention and management and core findings under each theme were supported by domain summaries in our final interpretation of the results. To maintain the rigors, Lincoln and Guba's parallel quality criteria of trustworthiness was used particularly, credibility, dependability, transferability, confirmability and reflexivity. RESULTS: Total of 26 service providers, program managers, and focal persons were participated through four focus group discussion and five key informant interviews. The study explored factors for engagement of health care providers in the prevention and management of multidrug resistant tuberculosis in five emergent themes such as patients' causes, perceived susceptibility, seeking support, professional incompetence and poor linkage of the health care facilities. Our findings also suggest that service providers require additional training, particularly in programmatic management of drug-resistant tuberculosis. CONCLUSION: The study explored five emergent themes: patient's underlying causes, seeking support, perceived susceptibility, professionals' incompetence and health facilities poor linkage. Community awareness creation to avoid fear of discrimination through provision of support for those with multidrug resistant tuberculosis is expected from health care providers using social behavioral change communication strategies. Furthermore, program managers need to follow the recommendations of World Health Organization for engaging healthcare professionals in the prevention and management of multidrug resistant tuberculosis and cascade trainings in clinical programmatic management of the disease for healthcare professionals.

Performance of the BD MAX MDR-TB assay in a clinical setting and its impact on the clinical course of patients with pulmonary tuberculosis: a retrospective before-after study.

BACKGROUND: Missing isoniazid (INH) resistance during tuberculosis (TB) diagnosis can worsen the outcomes of INH-resistant TB. The BD MAX MDR-TB assay (BD MAX) facilitates the rapid detection of TB and INH and rifampin (RIF) resistance; however, data related to its performance in clinical setting remain limited. Moreover, its effect on treatment outcomes has not yet been studied. METHODS: We compared the performance of BD MAX for the detection of INH/RIF resistances to that of the line probe assay (LPA) in patients with pulmonary TB (PTB), using the results of a phenotypic drug sensitivity test as a reference standard. The treatment outcomes of patients who used BD MAX were compared with those of patients who did not. RESULTS: Of the 83 patients included in the study, the BD MAX was used for an initial PTB diagnosis in 39 patients. The sensitivity of BD MAX for detecting PTB was 79.5%. The sensitivity and specificity of BD MAX for INH resistance were both 100%, whereas these were 50.0% and 95.8%, respectively, for RIF resistance. The sensitivity and specificity of BD MAX were comparable to those of LPA. The BD MAX group had a shorter time interval from specimen request to the initiation of anti-TB drugs (2.0 days vs. 5.5 days, p=0.001). CONCLUSION: BD MAX showed comparable performance to conventional tests for detecting PTB and INH/RIF resistances. The implementation of BD MAX as a diagnostic tool for PTB resulted in a shorter turnaround time for the initiation of PTB treatment.

South African adolescents' lived experiences of acquired hearing loss following multidrug-resistant tuberculosis treatment.

Objective: The impact of acquiring hearing loss might be exacerbated during adolescence, as this normal transition from childhood to adulthood is characterised by identity construction and social intensity. This study aimed to describe the lived experiences of South African adolescents with acquired hearing loss following aminoglycoside treatment for multidrug resistant tuberculosis. Design: The study adopted a descriptive phenomenological design and in-depth, semi-structured interviews were conducted in English, isiZulu and Afrikaans. The data was managed and analysed according to a modified version of Hycner's framework. Study sample: Six participants aged 16-24 years with bilateral, mild to profound hearing loss acquired from aminoglycoside treatment were recruited from two South African provinces. Results: Three themes emerged which created a triple burden for participants. They endured socio-economic hardship encompassing limited economic and emotional support. Participants battled the consequences of life-threatening MDR-TB including illness, hospitalisation, stigma, and other challenges. Finally, participants were left with life-changing hearing loss. Conclusion: The findings indicate the necessity of holistic management of adolescents with aminoglycoside-related acquired hearing loss and serves as motivation to improve ototoxic monitoring practices and patient uptake of monitoring services and calls for the cessation, or at least cautious use, of aminoglycosides.

Treatment Outcome of Drug-Resistant Skeletal Tuberculosis: A Retrospective Analysis.

Background: Management outcomes of drug-resistant (DR) osteoarticular tuberculosis (OATB) is dismal as in pre-ATT era (1905). The studies documenting treatment outcome of DR-OATB are scarce; hence, present retrospective analysis was conducted to evaluate outcome of consecutive cases of DR-OATB. Methods: 45 consecutive patients of suspected DR-OATB were treated from 2010 onwards. Tissue samples were submitted for AFB smear, cytology/histology, liquid culture, CBNAAT/LPA besides gram's staining and aerobic/anaerobic culture. Patients were treated by individualized second-line ATT till documenting healed status by contrast MRI/PET. The changes in neurological deficit, deformities, and drug-induced adverse events were documented. Results: 37/45 patients, 15 males and 22 females, mean age 26.89 years were followed. DR was suspected observing poor clinico-radiological response/appearance of fresh lesions on ATT. All showed no growth on aerobic/anaerobic pyogenic culture. 29 (78%) had microbiologically proven drug resistance and 8 (22%) were labeled as clinical drug resistance (CDR). 18/29 had multi-drug resistance. Mean prior ATT intake was 12.03 months 15 (40%) underwent surgical decompression. Mean duration of second-line ATT was 22.5 months (9-36 months). All patients achieved healed status with 8 (21%) developed side effects, most commonly hepatotoxicity, ototoxicity, and psychiatric disturbances. Average follow-up after completion of ATT was 40.5 months. Conclusion: We report a large series where patients of DR-OATB were suspected on clinical criteria, investigated by DST, and treated. Patients with proven drug resistance were treated by individualized second-line ATT. CDR cases were treated by MDR protocol. Genotypic DST (CBNAAT/LPA) improved demonstration of DR. We demonstrated healed status on MRI/PET with no recurrence at minimum 2-year follow-up.

Closure of TB pulmonary cavern using endobronchial valve placement.

INTRODUCTION: Enhancing the efficacy of treatment for Multi-Drug Resistant (MDR) and Extensively Drug Resistant (XDR) Tuberculosis has prompted exploration into adjunctive therapies, such as Endobronchial Valve Placement (EVP) in addition to pharmacological interventions. MATERIALS AND METHODS: EVP was performed utilizing a combination of rigid and flexible bronchoscopes to address airway hemorrhage and facilitate closure of TB cavities. The procedure involved the deployment of large valves (12 mm and 17 mm), necessitating the utilization of a rigid bronchoscope. RESULTS: Sputum conversion was confirmed through culture analysis after one month, and chest CT scans revealed complete closure of the tuberculous cavity five months post the EVP procedure. CONCLUSION: We posit that when used in conjunction with anti-TB chemotherapy, this method holds promise for shortening treatment duration and improving overall efficacy.

Characteristic SNPs defining the major multidrug-resistant Mycobacterium tuberculosis clusters identified by EuSeqMyTB to support routine surveillance, EU/EEA, 2017 to 2019.

BackgroundThe EUSeqMyTB project, conducted in 2020, used whole genome sequencing (WGS) for surveillance of drug-resistant Mycobacterium tuberculosis in the European Union/European Economic Area (EU/EEA) and identified 56 internationally clustered multidrug-resistant (MDR) tuberculosis (TB) clones.AimWe aimed to define and establish a rapid and computationally simple screening method to identify probable members of the main cross-border MDR-TB clusters in WGS data to facilitate their identification and track their future spread.MethodsWe screened 34 of the larger cross-border clusters identified in the EuSeqMyTB pilot study (2017-19) for characteristic single nucleotide polymorphism (SNP) signatures that could identify and define members of each cluster. We also linked this analysis with published clusters identified in previous studies and identified more distant genetic relationships between some of the current clusters.ResultsA panel of 30 characteristic SNPs is presented that can be used as an initial (routine) screen for members of each cluster. For four of the clusters, no unique defining SNP could be identified; three of these are closely related (within approximately 20 SNPs) to one or more other clusters and likely represent a single established MDR-TB clade composed of multiple recent subclusters derived from the previously described ECDC0002 cluster.ConclusionThe identified SNP signatures can be integrated into routine pipelines and contribute to the more effective monitoring, rapid and widespread screening for TB. This SNP panel will also support accurate communication between laboratories about previously identified internationally transmitted MDR-TB genotypes.