National Tuberculosis Programme Research Articles

Impact and cost-effectiveness of the 6-month BPaLM regimen for rifampicin-resistant tuberculosis in Moldova: A mathematical modeling analysis.

Emerging evidence suggests that shortened, simplified treatment regimens for rifampicin-resistant tuberculosis (RR-TB) can achieve comparable end-of-treatment (EOT) outcomes to longer regimens. We compared a 6-month regimen containing bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) to a standard of care strategy using a 9- or 18-month regimen depending on whether fluoroquinolone resistance (FQ-R) was detected on drug susceptibility testing (DST). The primary objective was to determine whether 6 months of BPaLM is a cost-effective treatment strategy for RR-TB. We used genomic and demographic data to parameterize a mathematical model estimating long-term health outcomes measured in quality-adjusted life years (QALYs) and lifetime costs in 2022 USD ($) for each treatment strategy for patients 15 years and older diagnosed with pulmonary RR-TB in Moldova, a country with a high burden of TB drug resistance. For each individual, we simulated the natural history of TB and associated treatment outcomes, as well as the process of acquiring resistance to each of 12 anti-TB drugs. Compared to the standard of care, 6 months of BPaLM was cost-effective. This strategy was estimated to reduce lifetime costs by $3,366 (95% UI: [1,465, 5,742] p < 0.001) per individual, with a nonsignificant change in QALYs (-0.06; 95% UI: [-0.49, 0.032] p = 0.790). For those stopping moxifloxacin under the BPaLM regimen, continuing with BPaL plus clofazimine (BPaLC) provided more QALYs at lower cost than continuing with BPaL alone. Strategies based on 6 months of BPaLM had at least a 93% chance of being cost-effective, so long as BPaLC was continued in the event of stopping moxifloxacin. BPaLM for 6 months also reduced the average time spent with TB resistant to amikacin, bedaquiline, clofazimine, cycloserine, moxifloxacin, and pyrazinamide, while it increased the average time spent with TB resistant to delamanid and pretomanid. Sensitivity analyses showed 6 months of BPaLM to be cost-effective across a broad range of values for the relative effectiveness of BPaLM, and the proportion of the cohort with FQ-R. Compared to the standard of care, 6 months of BPaLM would be expected to save Moldova's national TB program budget $7.1 million (95% UI: [1.3 million, 15.4 million] p = 0.002) over the 5-year period from implementation. Our analysis did not account for all possible interactions between specific drugs with regard to treatment outcomes, resistance acquisition, or the consequences of specific types of severe adverse events, nor did we model how the intervention may affect TB transmission dynamics. Compared to standard of care, longer regimens, the implementation of the 6-month BPaLM regimen could improve the cost-effectiveness of care for individuals diagnosed with RR-TB, particularly in settings with a high burden of drug-resistant TB. Further research may be warranted to explore the impact and cost-effectiveness of shorter RR-TB regimens across settings with varied drug-resistant TB burdens and national income levels.

Assessing intersectional gender analysis in Nepal’s health management information system: a case study on tuberculosis for inclusive health systems

BackgroundTuberculosis (TB) remains a major public health problem in Nepal, high in settings marked by prevalent gender and social inequities. Various social stratifiers intersect, either privileging or oppressing individuals based on their characteristics and contexts, thereby increasing risks, vulnerabilities and marganilisation associated with TB. This study aimed to assess the inclusiveness of gender and other social stratifiers in key health related national policies and the Health Management Information System (HMIS) of National Tuberculosis Programme (NTP) by conducting an intersectional analysis of TB cases recorded via HMIS.MethodsA desk review of key policies and the NTP’s HMIS was conducted. Retrospective intersectional analysis utilized two secondary data sources: annual NTP report (2017–2021) and records of 628 TB cases via HMIS 6.5 from two TB centres (2017/18–2018/19). Chi-square test and multi-variate analysis was used to assess the association between social stratifers and types of TB, registration category and treatment outcome.ResultsGender, social inclusion and concept of intersectionality are incorporated into various health policies and strategies but lack effective implementation. NTP has initiated the collection of age, sex, ethnicity and location data since 2014/15 through the HMIS. However, only age and sex disaggregated data are routinely reported, leaving recorded social stratifiers of TB patients static without analysis and dissemination. Furthermore, findings from the intersectional analysis using TB secondary data, showed that male more than 25 years exhibited higher odds [adjusted odds ratio (aOR) = 4.95, 95% confidence interval (CI): 1.60–19.06, P = 0.01)] of successful outcome compared to male TB patients less than 25 years. Similarly, sex was significantly associated with types of TB (P < 0.05) whereas both age (P < 0.05) and sex (P < 0.05) were significantly associated with patient registration category (old/new cases).ConclusionsThe results highlight inadequacy in the availability of social stratifiers in the routine HMIS. This limitation hampers the NTP’s ability to conduct intersectional analyses, crucial for unveiling the roles of other social determinants of TB. Such limitation underscores the need for more disaggregated data in routine NTP to better inform policies and plans contributing to the development of a more responsive and equitable TB programme and effectively addressing disparities.

Tuberculosis prevalence and demographic characteristics of population in Azad Jammu and Kashmir (Pakistan): A retrospective study.

Tuberculosis (TB) remains a serious problem for public health and a leading cause of death after COVID-19 and superior to even HIV/AIDS. It is a social health issue and can cause stigma and economic loss as the person cannot perform professionally due to lethargy caused by disease. It is a retrospective study done on data from National TB program Muzaffarabad chapter. The details were noted on SPSS and analysis was done to find important demographic characteristics. The total number of patients was 3441; among which 48.76% were males. Most of them (81.11%) belonged to the Muzaffarabad division of Azad Jammu and Kahmir (AJK). The microbiologically or culture positive cases were 440. Rifampicin resistance was present in 147 cases, further categorized as high (n = 143), very high (n = 3), or true positive (n = 1) resistance. Muti drug resistance was found in 19 cases. The microscopy culture is more sensitive (AUC = 0.511) than MTB/RIF or serology (AUC = 0.502) according to ROC. The rate of positive smear results is not very satisfactory in the present study as it cannot detect dormant or latent cases. There is a need to establish more sensitive tests for detection of cases and more research to combat the disease.

Cost-consequence analysis of ambulatory clinic- and home-based multidrug-resistant tuberculosis management models in Eswatini.

We compared the cost-consequence of a home-based multidrug-resistant tuberculosis (MDR-TB) model of care, based on task-shifting of directly observed therapy (DOT) and MDR-TB injection administration to lay health workers, to a routine clinic-based strategy within an established national TB programme in Eswatini. Data on costs and effects of the two ambulatory models of MDR-TB care was collected using documentary data and interviews in the Lubombo and Shiselweni regions of Eswatini. Health system, patient and caregiver costs were assessed in 2014 in US$ using standard methods. Cost-consequence was calculated as the cost per patient successfully treated. In the clinic-based and home-based models of care, respectively, a total of 96 and 106 MDR-TB patients were enrolled in 2014, with treatment success rates of 67.8% and 82.1%. Health system costs per patient treated were slightly lower in the home-based strategy (US$19 598) compared to the clinic-based model (US$20 007). The largest costs in both models were for inpatient care, administration of DOT and injectable treatment, and drugs. Costs incurred by patients and caregivers were considerably higher in the clinic-based model of care due to the higher direct travel costs to the nearest clinic to receive DOT and injections daily. In total, MDR patients in the clinic-based strategy incurred average costs of US$670 compared to US$275 for MDR-TB patients in the home-based model. MDR-TB patients in the home-based programme, where DOT and injections was provided in their homes, only incurred out-of-pocket travel expenses for monthly outpatient treatment monitoring visits averaging US$100. The cost per successfully treated patient was US$31 106 and US$24 157 in the clinic-based and home-based models of care, respectively. The analysis showed that, in addition to the health benefits, direct and indirect costs for patients and their caregivers were lower in the home-based care model. The home-based strategy used less resources and generated substantial health and economic benefits, particularly for patients and their caregivers, and decision makers can consider this approach as an alternative to expand and optimise MDR-TB control in resource-limited settings. Further research to understand the appropriate mix of treatment support components that are most important for optimal clinical and public health outcomes in the ambulatory home-based model of MDR-TB care is necessary.

Private Sector Involvement in Tuberculosis Control in An Urban City of Western India– A Cross-Sectional Study

Background: In India, TB diagnosis and treatment practices among Private Practitioners (PPs) vary widely and are not properly regulated by the national TB program. Despite their irrational and inequitable practises, PPs remain an important and preferred primary care provider for many people. The study was done to with the objectives to describe different diagnosis and treatment practices of Tuberculosis among private practitioners and their involvement in National Tuberculosis Elimination Program (NTEP). Material and Methods: A cross sectional study was performed among 303 PPs during October 2020 to March 2021 by using stratified random sampling to select private practitioners based on their speciality. Results: Most preferred investigation was Chest X ray (45.2%) followed by sputum smear microscopy (29.7%). Only 71.3% PPs practiced the correct regimen for new cases of Pulmonary TB according to NTEP. More than half of the PPs had TB training (59.7%). Majority of the PPs (90.1%) were involved in NTEP mainly by referral of TB patients to local government centres for treatment purpose. Conclusion: Preferred investigation for diagnosis of pulmonary TB was chest X-ray followed by sputum examination among PPs. The treatment regimen and duration of treatment varies among PPs as per their clinical judgement and practice.

Towards comprehensive clinical trials for new tuberculosis drug regimens: policy recommendations from a stakeholder analysis

BackgroundResearch and development (R&D) of new drugs and regimens against tuberculosis (TB) is evolving to meet new challenges and face limited investments in the sector. To effectively improve and fill...

A pragmatic randomized controlled trial to evaluate the efficacy and safety of an oral short-course regimen including bedaquiline for the treatment of patients with multidrug-resistant tuberculosis in China: study protocol for PROSPECT

IntroductionThe lack of safe, effective, and simple short-course regimens (SCRs) for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment has significantly impeded TB control efforts in China.MethodsThis phase 4, randomized, open-label, controlled, non-inferiority trial aims to assess the efficacy and safety of a 9-month all-oral SCR containing bedaquiline (BDQ) versus an all-oral SCR without BDQ for adult MDR-TB patients (18–65 years) in China. The trial design mainly mirrors that of the “Evaluation of a Standardized Treatment Regimen of Anti-Tuberculosis Drugs for Patients with MDR-TB” (STREAM) stage 2 study, while also incorporating programmatic data from South Africa and the 2019 consensus recommendations of Chinese MDR/RR-TB treatment experts. Experimental arm participants will receive a modified STREAM regimen C that replaces three group C drugs, ethambutol (EMB), pyrazinamide (PZA), and prothionamide (PTO), with two group B drugs, linezolid (LZD) and cycloserine (CS), while omitting high-dose isoniazid (INH) for confirmed INH-resistant cases. BDQ duration will be extended from 6 to 9 months for participants with Mycobacterium tuberculosis-positive sputum cultures at week 16. The control arm will receive a modified STREAM regimen B without high-dose INH and injectable kanamycin (KM) that incorporates experimental arm LZD and CS dosages, treatment durations, and administration methods. LZD (600 mg) will be given daily for ≥ 24 weeks as guided by observed benefits and harm. The primary outcome measures the proportion of participants with favorable treatment outcomes at treatment completion (week 40), while the same measurement taken at 48 weeks post-treatment completion is the secondary outcome. Assuming an α = 0.025 significance level (one-sided test), 80% power, 15% non-inferiority margin, and 10% lost to follow-up rate, each arm requires 106 participants (212 total) to demonstrate non-inferiority.DiscussionPROSPECT aims to assess the safety and efficacy of a BDQ-containing SCR MDR-TB treatment at seventeen sites across China, while also providing high-quality data to guide SCRs administration under the direction of the China National Tuberculosis Program for MDR-TB. Additionally, PROSPECT will explore the potential benefits of extending the administration of the 9-month BDQ-containing SCR for participants without sputum conversion by week 16.Trial registrationClinicalTrials.gov NCT05306223. Prospectively registered on 16 March 2022 at https://clinicaltrials.gov/ct2/show/NCT05306223?term=NCT05306223&draw=1&rank=1 {2}.

Factors Affecting the Success of the National Tuberculosis Control Program in Hospitals in Indonesia Based on the National Hospital Accreditation Standards (SNARS): A Scoping Review

&lt;div&gt;&lt;table cellspacing="0" cellpadding="0" align="left"&gt;&lt;tbody&gt;&lt;tr&gt;&lt;td align="left" valign="top"&gt;&lt;p&gt;&lt;em&gt;Tuberculosis (TB) is an infectious disease that is one of the leading causes of health problems worldwide and in developing countries. Hospitals have a very important role in the success of Tuberculosis control programs. Tuberculosis prevention and control encompass a range of health initiatives that are designed to safeguard public health, mitigate morbidity, disability, and death rates, disrupt the spread of the illness, combat medication resistance, and alleviate the adverse consequences associated with Tuberculosis. This scoping review aims to assess the factors that influence the success of the national tuberculosis control program in hospitals based on the National Hospital Accreditation Standards. A scoping review was conducted in this work, utilizing four databases: Google Scholar, Ebsco, Pro Quest, and Science Direct. The PRISMA Flowchart is a tool used to guide the process of selecting research publications. The inclusion exclusion criteria in the article search were limited to the last 10 years, starting from 2014 to 2023. The results of the scoping review showed that the factors influencing the success of the national tuberculosis program in hospitals based on the National Hospital Accreditation Standards are health promotion, early detection of tuberculosis or health screening, tuberculosis surveillance, risk factor control, surveillance of tuberculosis case finding and treatment, provision of immunity with vaccines and provision of tuberculosis preventive drugs. And in an effort to enhance the effectiveness of the Tuberculosis program, the government, hospitals, and communities should prioritize the implementation of the Directly Observed Treatment Shortcourse program in hospitals to ensure its smooth execution&lt;/em&gt;&lt;/p&gt;&lt;p&gt;&lt;em&gt; &lt;/em&gt;&lt;/p&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/tbody&gt;&lt;/table&gt;&lt;/div&gt;&lt;strong&gt;&lt;em&gt;Keywords: Tuberculosis, Hospital, Program&lt;/em&gt;&lt;/strong&gt;

Is convenience really king? Comparative evaluation of catastrophic costs due to tuberculosis in the public and private healthcare sectors of Viet Nam: a longitudinal patient cost study

BackgroundIn Viet Nam, tuberculosis (TB) represents a devastating life-event with an exorbitant price tag, partly due to lost income from daily directly observed therapy in public sector care. Thus, persons with TB may seek care in the private sector for its flexibility, convenience, and privacy. Our study aimed to measure income changes, costs and catastrophic cost incurrence among TB-affected households in the public and private sector.MethodsBetween October 2020 and March 2022, we conducted 110 longitudinal patient cost interviews, among 50 patients privately treated for TB and 60 TB patients treated by the National TB Program (NTP) in Ha Noi, Hai Phong and Ho Chi Minh City, Viet Nam. Using a local adaptation of the WHO TB patient cost survey tool, participants were interviewed during the intensive phase, continuation phase and post-treatment. We compared income levels, direct and indirect treatment costs, catastrophic costs using Wilcoxon rank-sum and chi-squared tests and associated risk factors between the two cohorts using multivariate regression.ResultsThe pre-treatment median monthly household income was significantly higher in the private sector versus NTP cohort (USD 868 vs USD 578; P = 0.010). However, private sector treatment was also significantly costlier (USD 2075 vs USD 1313; P = 0.005), driven by direct medical costs which were 4.6 times higher than costs reported by NTP participants (USD 754 vs USD 164; P < 0.001). This resulted in no significant difference in catastrophic costs between the two cohorts (Private: 55% vs NTP: 52%; P = 0.675). Factors associated with catastrophic cost included being a single-person household [adjusted odds ratio (aOR = 13.71; 95% confidence interval (CI): 1.36–138.14; P = 0.026], unemployment during treatment (aOR = 10.86; 95% CI: 2.64–44.60; P < 0.001) and experiencing TB-related stigma (aOR = 37.90; 95% CI: 1.72–831.73; P = 0.021).ConclusionsPersons with TB in Viet Nam face similarly high risk of catastrophic costs whether treated in the public or private sector. Patient costs could be reduced through expanded insurance reimbursement to minimize direct medical costs in the private sector, use of remote monitoring and multi-week/month dosing strategies to avert economic costs in the public sector and greater access to social protection mechanism in general.

Singapore tuberculosis (TB) clinical management guidelines 2024: A modified Delphi adaptation of international guidelines for drug-susceptible TB infection and pulmonary disease

Introduction: Tuberculosis (TB) remains endemic in Singapore. Singapore’s clinical practice guidelines for the management of tuberculosis were first published in 2016. Since then, there have been major new advances in the clinical management of TB, ranging from diagnostics to new drugs and treatment regimens. The National TB Programme convened a multidisciplinary panel to update guidelines for the clinical management of drug-susceptible TB infection and disease in Singapore, contextualising current evidence for local practice. Method: Following the ADAPTE framework, the panel systematically reviewed, scored and synthesised English-language national and international TB clinical guidelines published from 2016, adapting recommendations for a prioritised list of clinical decisions. For questions related to more recent advances, an additional primary literature review was conducted via a targeted search approach. A 2-round modified Delphi process was implemented to achieve consensus for each recommendation, with a final round of edits after consultation with external stakeholders. Results: Recommendations for 25 clinical questions spanning screening, diagnosis, selection of drug regimen, monitoring and follow-up of TB infection and disease were formulated. The availability of results from recent clinical trials led to the inclusion of shorter treatment regimens for TB infection and disease, as well as consensus positions on the role of newer technologies, such as computer-aided detection-artificial intelligence products for radiological screening of TB disease, next-generation sequencing for drug-susceptibility testing, and video observation of treatment. Conclusion: The panel updated recommendations on the management of drug-susceptible TB infection and disease in Singapore.

Singapore tuberculosis (TB) clinical management guidelines 2024: A modified Delphi adaptation of international guidelines for drug-susceptible TB infection and pulmonary disease

Introduction: Tuberculosis (TB) remains endemic in Singapore. Singapore’s clinical practice guidelines for the management of tuberculosis were first published in 2016. Since then, there have been major new advances in the clinical management of TB, ranging from diagnostics to new drugs and treatment regimens. The National TB Programme convened a multidisciplinary panel to update guidelines for the clinical management of drug-susceptible TB infection and disease in Singapore, contextualising current evidence for local practice. Method: Following the ADAPTE framework, the panel systematically reviewed, scored and synthesised English-language national and international TB clinical guidelines published from 2016, adapting recommendations for a prioritised list of clinical decisions. For questions related to more recent advances, an additional primary literature review was conducted via a targeted search approach. A 2-round modified Delphi process was implemented to achieve consensus for each recommendation, with a final round of edits after consultation with external stakeholders. Results: Recommendations for 25 clinical questions spanning screening, diagnosis, selection of drug regimen, monitoring and follow-up of TB infection and disease were formulated. The availability of results from recent clinical trials led to the inclusion of shorter treatment regimens for TB infection and disease, as well as consensus positions on the role of newer technologies, such as computer-aided detection-artificial intelligence products for radiological screening of TB disease, next-generation sequencing for drug-susceptibility testing, and video observation of treatment. Conclusion: The panel updated recommendations on the management of drug-susceptible TB infection and disease in Singapore.

Engagement of private health care facilities in TB management in Lusaka district of Zambia: lessons learned and achievements

BackgroundGlobally, at least 3 million TB patients are missed every year. In Zambia, the TB treatment coverage increased from 66% in 2020 to 92% in 2022. Involvement of all levels of health care service delivery is critical to finding all the missing TB patients.MethodsA survey was undertaken in 15 private facilities in Lusaka district of Zambia using a structured tool administered by project team and a district health team member. Data collected during the survey was analysed and results were used to determine the type of TB services that were offered as well as barriers and enablers to TB service provision. This was followed by a set of interventions that included; training and mentorship on active case finding and systematic TB screening, increased diagnostic capacity, provision of national recording and reporting tools and provision of TB medication through linkage with the National TB program (NTP). We report findings from the baseline survey and changes in presumptive TB identification and notification following interventions.ResultsMajor barriers to TB service delivery were the high cost of TB diagnostic testing and treatment in facilities where services were not supported by the National TB program; the mean cost was 33 (SD 33) and 93 (SD 148) for GeneXpert testing and a full course of treatment respectively. Pre-intervention, presumptive TB identification appeared to increase monthly by 4 (P = 0.000, CI=[3.00–5.00]). The monthly trends of presumptive TB identification during the intervention period increased by 5.32 (P = 0.000, [CI 4.31–6.33. Pre-intervention, the notification of TB appeared to decrease every month by -4.0 (P = 0.114, CI=[-9.00-0.10]) followed by an immediate increase in notifications of 13.94 TB patients (P = 0.001, CI [6.51, 21.36] in the first month on intervention. The monthly trends of notification during the intervention period changed by 0.34 (P = 0.000 [CI 0.19–0.48]). Private facility contribution to TB notification increased from 3 to 7%.ConclusionEngagement and inclusion of private health facilities in TB service provision through a systems strengthening approach can increase contribution to TB notification by private health facilities.

Aerosolization of viable Mycobacterium tuberculosis bacilli by tuberculosis clinic attendees independent of sputum-Xpert Ultra status

Potential Mycobacterium tuberculosis (Mtb) transmission during different pulmonary tuberculosis (TB) disease states is poorly understood. We quantified viable aerosolized Mtb from TB clinic attendees following diagnosis and through six months' follow-up thereafter. Presumptive TB patients (n=102) were classified by laboratory, radiological, and clinical features into Group A: Sputum-Xpert Ultra-positive TB (n=52), Group B: Sputum-Xpert Ultra-negative TB (n=20), or Group C: TB undiagnosed (n=30). All groups were assessed for Mtb bioaerosol release at baseline, and subsequently at 2 wk, 2 mo, and 6 mo. Groups A and B were notified to the national TB program and received standard anti-TB chemotherapy; Mtb was isolated from 92% and 90% at presentation, 87% and 74% at 2 wk, 54% and 44% at 2 mo and 32% and 20% at 6 mo, respectively. Surprisingly, similar numbers were detected in Group C not initiating TB treatment: 93%, 70%, 48% and 22% at the same timepoints. A temporal association was observed between Mtb bioaerosol release and TB symptoms in all three groups. Persistence of Mtb bioaerosol positivity was observed in ~30% of participants irrespective of TB chemotherapy. Captured Mtb bacilli were predominantly acid-fast stain-negative and poorly culturable; however, three bioaerosol samples yielded sufficient biomass following culture for whole-genome sequencing, revealing two different Mtb lineages. Detection of viable aerosolized Mtb in clinic attendees, independent of TB diagnosis, suggests that unidentified Mtb transmitters might contribute a significant attributable proportion of community exposure. Additional longitudinal studies with sputum culture-positive and -negative control participants are required to investigate this possibility.

Spatio-temporal characteristics of Tuberculosis in Ghana

Background Tuberculosis (TB) continues to be a prominent contributor to global mortality, standing as the second most fatal infectious disease and holding the seventh position among the top ten causes of death in Ghana. There is insufficient literature regarding the utilization of Bayesian hierarchical models, specifically within the framework of Integrated Nested Laplace Approximation (INLA), for examining the spatial and spatio-temporal dynamics of tuberculosis risk in Ghana. This study addresses this gap by determining TB hotspots regions in Ghana using the Bayesian modeling framework within the INLA. Methods TB data were sourced from the Ghana Health Service and National Tuberculosis Programme for the 10 administrative regions of Ghana, from 2008 to 2017. The relative risk of TB for each region and year was estimated utilizing Bayesian spatial and spatio-temporal modeling frameworks. Baseline predictors of TB risk were also considered. Maps for TB risks were created to visualized regions with TB hotspots. Model fitting and parameter estimation were conducted using R version 4.3.2. Results Among the baseline predictors, factors such as TB cure rate, TB success rate, knowledge about TB, HIV prevalence, percentage of literacy, and high income were found to be most significant in influencing the TB risk across the ten regions in Ghana. We noted an increased risk of TB infection in the Northern zone and the Eastern and Greater Accra regions in the Southern zone. Spatio-temporal distribution of TB infection risk was predominantly concentrated in the Southern zone. Clustering of TB risk was observed among neighboring regions. Conclusion To achieve a significant reduction in TB cases, it is essential to allocate resources to TB hotspots regions and also implement measures to control significant predictors of TB infection risk.

Global, regional, and national age-specific progress towards the 2020 milestones of the WHO End TB Strategy: a systematic analysis for the Global Burden of Disease Study 2021.

Global evaluations of the progress towards the WHO End TB Strategy 2020 interim milestones on mortality (35% reduction) and incidence (20% reduction) have not been age specific. We aimed to assess global, regional, and national-level burdens of and trends in tuberculosis and its risk factors across five separate age groups, from 1990 to 2021, and to report on age-specific progress between 2015 and 2020. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021) analytical framework to compute age-specific tuberculosis mortality and incidence estimates for 204 countries and territories (1990-2021 inclusive). We quantified tuberculosis mortality among individuals without HIV co-infection using 22 603 site-years of vital registration data, 1718 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, 680 site-years of mortality surveillance data, and 9 site-years of minimally invasive tissue sample (MITS) diagnoses data as inputs into the Cause of Death Ensemble modelling platform. Age-specific HIV and tuberculosis deaths were established with a population attributable fraction approach. We analysed all available population-based data sources, including prevalence surveys, annual case notifications, tuberculin surveys, and tuberculosis mortality, in DisMod-MR 2.1 to produce internally consistent age-specific estimates of tuberculosis incidence, prevalence, and mortality. We also estimated age-specific tuberculosis mortality without HIV co-infection that is attributable to the independent and combined effects of three risk factors (smoking, alcohol use, and diabetes). As a secondary analysis, we examined the potential impact of the COVID-19 pandemic on tuberculosis mortality without HIV co-infection by comparing expected tuberculosis deaths, modelled with trends in tuberculosis deaths from 2015 to 2019 in vital registration data, with observed tuberculosis deaths in 2020 and 2021 for countries with available cause-specific mortality data. We estimated 9·40 million (95% uncertainty interval [UI] 8·36 to 10·5) tuberculosis incident cases and 1·35 million (1·23 to 1·52) deaths due to tuberculosis in 2021. At the global level, the all-age tuberculosis incidence rate declined by 6·26% (5·27 to 7·25) between 2015 and 2020 (the WHO End TB strategy evaluation period). 15 of 204 countries achieved a 20% decrease in all-age tuberculosis incidence between 2015 and 2020, eight of which were in western sub-Saharan Africa. When stratified by age, global tuberculosis incidence rates decreased by 16·5% (14·8 to 18·4) in children younger than 5 years, 16·2% (14·2 to 17·9) in those aged 5-14 years, 6·29% (5·05 to 7·70) in those aged 15-49 years, 5·72% (4·02 to 7·39) in those aged 50-69 years, and 8·48% (6·74 to 10·4) in those aged 70 years and older, from 2015 to 2020. Global tuberculosis deaths decreased by 11·9% (5·77 to 17·0) from 2015 to 2020. 17 countries attained a 35% reduction in deaths due to tuberculosis between 2015 and 2020, most of which were in eastern Europe (six countries) and central Europe (four countries). There was variable progress by age: a 35·3% (26·7 to 41·7) decrease in tuberculosis deaths in children younger than 5 years, a 29·5% (25·5 to 34·1) decrease in those aged 5-14 years, a 15·2% (10·0 to 20·2) decrease in those aged 15-49 years, a 7·97% (0·472 to 14·1) decrease in those aged 50-69 years, and a 3·29% (-5·56 to 9·07) decrease in those aged 70 years and older. Removing the combined effects of the three attributable risk factors would have reduced the number of all-age tuberculosis deaths from 1·39 million (1·28 to 1·54) to 1·00 million (0·703 to 1·23) in 2020, representing a 36·5% (21·5 to 54·8) reduction in tuberculosis deaths compared to those observed in 2015. 41 countries were included in our analysis of the impact of the COVID-19 pandemic on tuberculosis deaths without HIV co-infection in 2020, and 20 countries were included in the analysis for 2021. In 2020, 50 900 (95% CI 49 700 to 52 400) deaths were expected across all ages, compared to an observed 45 500 deaths, corresponding to 5340 (4070 to 6920) fewer deaths; in 2021, 39 600 (38 300 to 41 100) deaths were expected across all ages compared to an observed 39 000 deaths, corresponding to 657 (-713 to 2180) fewer deaths. Despite accelerated progress in reducing the global burden of tuberculosis in the past decade, the world did not attain the first interim milestones of the WHO End TB Strategy in 2020. The pace of decline has been unequal with respect to age, with older adults (ie, those aged >50 years) having the slowest progress. As countries refine their national tuberculosis programmes and recalibrate for achieving the 2035 targets, they could consider learning from the strategies of countries that achieved the 2020 milestones, as well as consider targeted interventions to improve outcomes in older age groups. Bill & Melinda Gates Foundation.

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, &gt;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.

Differentiated TB care: Tamil Nadu's achievements, plans and implications for national TB programmes.

Differentiated TB care: Tamil Nadu's achievements, plans and implications for national TB programmes.

Epidemiology and treatment outcomes of recurrent tuberculosis in Tanzania from 2018 to 2021 using the National TB dataset.

Patients with recurrent TB have an increased risk of higher mortality, lower success rate, and a relatively feeble likelihood of treatment completion than those with new-onset TB. This study aimed to assess the epidemiology of recurrent TB in Tanzania; specifically, we aim to determine the prevalence of TB recurrence and factors associated with unfavourable treatment outcomes among patients with recurrent TB in Tanzania from 2018 to 2021. In this cross-sectional study, we utilized Tanzania's routinely collected national TB program data. The study involved a cohort of TB patients over a fixed treatment period registered in the TB and Leprosy case-based District Health Information System (DHIS2-ETL) database from 2018 to 2021 in Tanzania. We included patients' sociodemographic and clinical factors, facility characteristics, and TB treatment outcomes. We conducted bivariate analysis and multivariable multi-level mixed effects logistic regression of factors associated with TB recurrence and TB treatment outcomes to account for the correlations at the facility level. A purposeful selection method was used; the multivariable model included apriori selected variables (Age, Sex, and HIV status) and variables with a p-value <0.2 on bivariate analysis. The adjusted odds ratio and 95% confidence interval were recorded, and a p-value of less than 0.05 was considered statistically significant. A total of 319,717 participants were included in the study; the majority were adults aged 25-49 (44.2%, n = 141,193) and above 50 years (31.6%, n = 101,039). About two-thirds were male (60.4%, n = 192,986), and more than one-fifth of participants (22.8%, n = 72,396) were HIV positive. Nearly two in every hundred TB patients had a recurrent TB episode (2.0%, n = 6,723). About 10% of patients with recurrent TB had unfavourable treatment outcomes (9.6%, n = 519). The odds of poor treatment outcomes were two-fold higher for participants receiving treatment at the central (aOR = 2.24; 95% CI 1.33-3.78) and coastal zones (aOR = 2.20; 95% CI 1.40-3.47) than the northern zone. HIV-positive participants had 62% extra odds of unfavourable treatment outcomes compared to their HIV-negative counterparts (aOR = 1.62; 95% CI 1.25-2.11). Bacteriological TB diagnosis (aOR = 1.39; 95% CI 1.02-1.90) was associated with a 39% additional risk of unfavourable treatment outcomes as compared to clinical TB diagnosis. Compared to community-based DOT, patients who received DOT at the facility had 1.39 times the odds of poor treatment outcomes (aOR = 1.39; 95%CI 1.04-1.85). TB recurrence in Tanzania accounts for 2% of all TB cases, and it is associated with poor treatment outcomes. Unfavourable treatment outcomes were recorded in 10% of patients with recurrent TB. Poor TB treatment outcome was associated with HIV-positive status, facility-based DOT, bacteriologically confirmed TB and receiving treatment at the hospital level, differing among regions. We recommend post-treatment follow-up for patients with recurrent TB, especially those coinfected with HIV. We also propose close follow-up for patients treated at the hospital facility level and strengthening primary health facilities in TB detection and management to facilitate early treatment initiation.

Piloting the Complex Ground of Drug- Resistant Extrapulmonary Tuberculosis in Adolescent Females: Unraveling Challenges and shaping future Strategies

Introduction: Tuberculosis (TB) is a global infectious disease, causing approximately 10.6 million new cases and 1.6 million deaths in 2021, with 450,000 patients annually having rifampicin-resistant (RR)/multi-drug resistant (MDR) TB. Despite higher pulmonary TB notifications in males, TB in females remains a significant threat, reflecting potential barriers to healthcare access. Background: This study addresses the challenging landscape of Rifampicin-resistant extrapulmonary TB in adolescent females, aiming to unravel recurrence patterns and treatment complexities. It serves as a call to action, advocating for tailored interventions to mitigate the impact of drug-resistant TB in this vulnerable population. Overview: Adolescence poses unique challenges for individuals diagnosed with tuberculosis, especially for females who exhibit higher susceptibility, facing stigma and potential impacts on self-esteem. The presentation of drug-resistant tuberculosis in adolescents differs from early childhood, necessitating differentiated care; however, there's a notable lack of recognition and specific guidelines for this age group in national TB programs. W.H.O. outlines plan with a comprehensive five-year strategy, detailing ten crucial steps to improve tuberculosis prevention, treatment, and care for children and adolescents. Additionally, the Roadmap targets a 90% coverage in diagnosis and treatment services and aims to provide TB preventive treatment to 90% of those at high risk between 2023 and 2027. Rifampicin-resistant tuberculosis, comprising MDR and XDR types, requires microbiological confirmation through genotypic or phenotypic tests. Treatment in adolescents aligns with adult regimens, including novel drugs like Delanamid and Bedaquiline, with consideration for exposure history and drug susceptibility.

Direct benefit transfer for nutritional support of patients with TB in India—analysis of national TB program data of 3.7 million patients, 2018–2022

BackgroundPatients with TB have additional nutritional requirements and thus additional costs to the household. Ni-kshay Poshan Yojana(NPY) is a Direct Benefit Transfer (DBT) scheme under the National Tuberculosis Elimination Programme(NTEP) in India which offers INR 500 monthly to all notified patients with TB for nutritional support during the period of anti-TB treatment. Five years after its implementation, we conducted the first nationwide evaluation of NPY.MethodsIn our retrospective cohort study using programmatic data of patients notified with TB in nine randomly selected Indian states between 2018 and 2022, we estimated the proportion of patients who received at least one NPY instalment and the median time to receive the first instalment. We determined the factors associated (i) with non-receipt of NPY using a generalised linear model with Poisson family and log link and (ii) with time taken to receive first NPY benefit in 2022 using quantile regression at 50th percentile.ResultsOverall, 3,712,551 patients were notified between 2018 and 2022. During this period, the proportion who received at least one NPY instalment had increased from 56.9% to 76.1%. Non-receipt was significantly higher among patients notified by private sector (aRR 2.10;2.08,2.12), reactive for HIV (aRR 1.69;1.64,1.74) and with missing/undetermined diabetic status (aRR 2.02;1.98,2.05). The median(IQR) time to receive the first instalment had reduced from 200(109,331) days in 2018 to 91(51,149) days in 2022. Patients from private sector(106.9;106.3,107.4days), those with HIV-reactive (103.7;101.8,105.7days), DRTB(104.6;102.6,106.7days) and missing/undetermined diabetic status (115.3;114,116.6days) experienced longer delays.ConclusionsThe coverage of NPY among patients with TB had increased and the time to receipt of benefit had halved in the past five years. Three-fourths of the patients received at least one NPY instalment, more than half of whom had waited over three months to receive the first instalment. NTEP has to focus on timely transfer of benefits to enable patients to meet their additional nutritional demands, experience treatment success and avoid catastrophic expenditure.