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The measures undertaken to control COVID-19 have disrupted many platforms including tuberculosis (TB) healthcare services. Consequently, declines in TB notifications have been observed in various countries. We visualized changes over time in TB and SARS-CoV-2 infection notifications and reported on country-specific strategies to retain TB care and prevention services in Kyrgyzstan, Nigeria, Tanzania, and Vietnam. We collected and visualized quarterly, retrospective, and country-specific data (Quarter (Q) 1 2018- Q1 2021) on SARS-CoV-2 infection and TB notifications. Additionally, we conducted a country-specific landscape assessment on COVID-19 measures, including lockdowns, operational level strategy of TB care and prevention services, and strategies employed to recover and retain those services. We used negative binomial regression models to assess the association between the installation of COVID-19 measures and changes in TB notifications. TB notifications declined in Kyrgyzstan and Vietnam, and (slightly) increased in Nigeria and Tanzania. The changes in TB notifications were associated with the installation of various COVID-19 prevention measures for Kyrgyzstan and Vietnam (declines) and Nigeria (increases). All countries reported reduced TB screening and testing activities. Countries reported the following strategies to retain TB prevention and care services: digital solutions for treatment adherence support, capacity building, and monitor & evaluation activities; adjustment in medication supply/delivery & quantity, including home delivery, pick up points, and month supply; integrated TB/COVID-19 screening & diagnostic platform; and the use of community health care workers. Following the COVID-19 pandemic, we did not observe consistent changes in TB notifications across countries. However, all countries reported lower operating levels of TB prevention and care services. Digital health solutions, community-based interventions, and the integration of COVID-19 and TB testing services were employed to recover and retain those services.

There is uncertainty about the contribution that social support interventions (SSI) can have in mitigating the personal, social and economic costs of tuberculosis (TB) treatment on patients, and improving treatment outcomes. To identify psycho-emotional (PE) and socio-economic (SE) interventions provided to TB patients and to assess the effects of these interventions on treatment adherence and treatment outcomes. We searched PubMed and Embase from 1 January 1990-15 March 2015 and abstracts of the Union World Conference on Lung Health from 2010-2014 for studies reporting TB treatment adherence and treatment outcomes following SSI. Studies measuring the effects of PE or SE interventions on TB treatment adherence, treatment outcomes, and/or financial burden. Two reviewers independently assessed titles and abstracts for inclusion of articles. One reviewer reviewed full text articles and the reference list of selected studies. A second reviewer double checked all extracted information against the articles. Twenty-five studies were included in the qualitative analysis; of which eighteen were included in the meta-analysis. Effects were pooled from 11 Randomized Controlled Trials (RCTs), including 9,655 participants with active TB. Meta-analysis showed that PE support (RR 1.37; CI 1.08-1.73), SE support (RR 1.08; CI 1.03-1.13) and combined PE and SE support (RR 1.17; CI 1.12-1.22) were associated with a significant improvement of successful treatment outcomes. Also PE support, SE support and a combination of these types of support were associated with reductions in unsuccessful treatment outcomes (PE: RR 0.46; CI 0.22-0.96, SE: RR 0.78; CI 0.69-0.88 and Combined PE and SE: RR 0.42; CI 0.23-0.75). Evidence on the effect of PE and SE interventions on treatment adherence were not meta-analysed because the interventions were too heterogeneous to pool. No evidence was found to show whether SE reduced the financial burden for TB patients. Our review and meta-analysis concluded that PE and SE interventions are associated with beneficial effects on TB treatment outcomes. However, the quality of evidence is very low and future well-designed evaluation studies are needed.

Abstract Background Tuberculosis (TB) is the fourth leading cause of death in Indonesia. In 2015, the World Health Organization estimated that nearly two-thirds of the TB patients in Indonesia had not been notified, and the status of their care remained unknown. As such, Indonesia is home to nearly 20% of the world’s “missing” TB patients. Understanding where patients go for care may enable strategic planning of services to better reach them. Methods A patient pathway analysis (PPA) was conducted to assess the alignment between patient care seeking and the availability of TB diagnostic and treatment services at the national and subnational level in Indonesia. Results The PPA results revealed that only 20% of patients encountered diagnostic capacity at the location where they first sought care. Most initial care seeking occurred in the private sector and case notification lagged behind diagnostic confirmation in the public sector. Conclusions The PPA results emphasize the role that the private sector plays in TB patient care seeking and suggested a need for differentiated approaches, by province, to respond to variances in care-seeking patterns and the capacities of public and private providers.

There are numerous challenges in delivering appropriate treatment for multidrug-resistant tuberculosis (MDR-TB) and the evidence base to guide those practices remains limited. We present the third updated Research Agenda for the programmatic management of drug-resistant TB (PMDT), assembled through a literature review and survey. Publications citing the 2008 research agenda and normative documents were reviewed for evidence gaps. Gaps were formulated into questions and grouped as in the 2008 research agenda: Laboratory Support, Treatment Strategy, Programmatically Relevant Research, Epidemiology, and Management of Contacts. A survey was distributed through snowball sampling to identify research priorities. Respondent priority rankings were scored and summarized by mean. Sensitivity analyses explored weighting and handling of missing rankings. Thirty normative documents and publications were reviewed for stated research needs; these were collapsed into 56 research questions across 5 categories. Of more than 500 survey recipients, 133 ranked priorities within at least one category. Priorities within categories included new diagnostics and their effect on improving treatment outcomes, improved diagnosis of paucibacillary and extra pulmonary TB, and development of shorter, effective regimens. Interruption of nosocomial transmission and treatment for latent TB infection in contacts of known MDR-TB patients were also top priorities in their respective categories. Results were internally consistent and robust. Priorities retained from the 2008 research agenda include shorter MDR-TB regimens and averting transmission. Limitations of recent advances were implied in the continued quest for: shorter regimens containing new drugs, rapid diagnostics that improve treatment outcomes, and improved methods of estimating burden without representative data. There is continuity around the priorities for research in PMDT. Coordinated efforts to address questions regarding shorter treatment regimens, knowledge of disease burden without representative data, and treatment for LTBI in contacts of known DR-TB patients are essential to stem the epidemic of TB, including DR-TB.

Background In the European Union and European Economic Area only 38% of multidrug-resistant tuberculosis patients notified in 2011 completed treatment successfully at 24 months’ evaluation. Socio-economic factors and patient factors such as demographic characteristics, behaviour and attitudes are associated with treatment outcomes. Characteristics of healthcare systems also affect health outcomes. This study was conducted to identify and better understand the contribution of health system components to successful treatment of multidrug-resistant tuberculosis. Methods We selected four European Union countries to provide for a broad range of geographical locations and levels of treatment success rates of the multidrug-resistant tuberculosis cohort in 2009. We conducted semi-structured interviews following a conceptual framework with representatives from policy and planning authorities, healthcare providers and civil society organisations. Responses were organised according to the six building blocks of the World Health Organization health systems framework. Results In the four included countries, Austria, Bulgaria, Spain, and the United Kingdom, the following healthcare system factors were perceived as key to achieving good treatment results for patients with multidrug-resistant tuberculosis: timely diagnosis of drug-resistant tuberculosis; financial systems that ensure access to a full course of treatment and support for multidrug-resistant tuberculosis patients; patient-centred approaches with strong intersectoral collaboration that address patients’ emotional and social needs; motivated and dedicated healthcare workers with sufficient mandate and means to support patients; and cross-border management of multidrug-resistant tuberculosis to secure continuum of care between countries. Conclusion We suggest that the following actions may improve the success of treatment for multidrug-resistant tuberculosis patients: deployment of rapid molecular diagnostic tests; development of context-specific treatment guidance and criteria for hospital admission and discharge in the European context; strengthening patient-centred approaches; development of collaborative mechanisms to ensure cross-border care, and development of long-term sustainable financing strategies.

IntroductionBedaquiline, pretomanid and linezolid (BPaL) is a new all oral, 6-month regimen comprised of bedaquiline, the new drug pretomanid and linezolid, endorsed by the WHO for use under operational research conditions in patients with extensively drug-resistant tuberculosis (XDR-TB). We quantified per-patient treatment costs and the 5-year budgetary impact of introducing BPaL in Indonesia, Kyrgyzstan and Nigeria.MethodsPer-patient treatment cost of BPaL regimen was compared head-to-head with the conventional XDR-TB treatment regimen for respective countries based on cost estimates primarily assessed using microcosting method and expected frequency of each TB service. The 5-year budget impact of gradual introduction of BPaL against the status quo was assessed using a Markov model that represented patient’s treatment management and outcome pathways.ResultsThe cost per patient completing treatment with BPaL was US$7142 in Indonesia, US$4782 in Kyrgyzstan and US$7152 in Nigeria – 57%, 78% and 68% lower than the conventional regimens in the respective countries. A gradual adoption of the BPaL regimen over 5 years would result in an 5-year average national TB service budget reduction of 17% (US$128 780) in XDR-TB treatment-related expenditure in Indonesia, 15% (US$700 247) in Kyrgyzstan and 32% (US$1 543 047) in Nigeria.ConclusionOur study demonstrates that the BPaL regimen can be highly cost-saving compared with the conventional regimens to treat patients with XDR-TB in high drug-resistant TB burden settings. This supports the rapid adoption of the BPaL regimen to address the significant programmatic and clinical challenges in managing patients with XDR-TB in high DR-TB burden countries.

IntroductionThe TriAD study will assess the Xpert MTB/XDR (Xpert XDR; Cepheid) assay to detect tuberculosis (TB) drug resistance in sputum testing positive for TB to rapidly triage and treat patients with a short all-oral treatment regimen.Methods and analysisIn this study, approximately 4800 Xpert MTB/RIF or Ultra MTB-positive patients (irrespective of rifampicin (RIF) resistance (RR) status) from several clinical sites across South Africa, Nigeria and Ethiopia will be enrolled over 18–24 months and followed-up for approximately 6 months post-TB treatment completion. Participants will be enrolled into one of two cohorts based on Xpert MTB/RIF and Xpert XDR results: Mycobacterium tuberculosis (M.tb) positive participants with RR in Cohort 1 (n=880) and M.tb positive RIF susceptible TB patients with isoniazid mono-resistance irrespective of presence of resistance to fluoroquinolones, second-line injectable drugs or ethionamide in Cohort 2 (n=400). Cohort 1 will be compared with historical cohorts from each implementing sites. The primary study outcomes include time to initiation of an appropriate treatment regimen by resistance profile and the proportion of patients with favourable treatment outcomes compared with historical cohorts from each of the implementing sites. Secondary outcomes include feasibility, acceptability and cost-effectiveness of this approach to inform policies and guidelines for programmatic implementation of this triage and treat model for drug-resistant tuberculosis management. Utility of the tuberculosis molecular bacterial load assay (TB-MBLA) for real-time treatment response assessment will also be evaluated.Ethics and disseminationThe University of KwaZulu-Natal Biomedical Research Ethics Committee (BREC) and local research committees have provided ethical review and approval (BREC/00002654/2021, HREC 210805, NHREC/01/01/2007 and EPHI-IRB-459–2022). The South African Health Products Regulatory Authority (SAHPRA) have granted regulatory approval for the TRiAD Study (SAHPRA MD20211001). Trial results will be disseminated through conference presentations, peer-reviewed publications and the clinical trial registry.Trial registration numberClinicaltrials.gov; Trial registration number: NCT05175794; South African National Clinical Trials Register (SANCTR DOH-27-012022-4720)

Background Data on tuberculosis (TB) among health care workers (HCW) and TB infection control (TBIC) indicators are rarely available at national level. We assessed multi-year trends in notification data of TB among HCW and explored possible associations with TBIC indicators. Methods Notified TB incidence among HCW and 3 other TBIC indicators were collected annually from all 64 provincial and 3 national TB facilities in Vietnam. Time trends in TB notification between 2009 and 2013 were assessed using linear regression analysis. Multivariate regression models were applied to assess associations between the facility-specific 5-year notification rate and TBIC indicators. Results Forty-seven (70 %) of 67 facilities contributed data annually over five years; 15 reported at least one HCW with TB in 2009 compared to six in 2013. The TB notification rate dropped from 593 to 197 per 100,000 HCW (p trend  = 0.02). Among 104 TB cases reported, 30 were employed at TB wards, 24 at other clinical wards, ten in the microbiology laboratory, six at the MDR-TB ward, and 34 in other positions. The proportion of facilities with a TBIC plan and focal person remained relatively stable between 70 % and 84 %. The proportion of facilities providing personal protective equipment (PPE) to their staff increased over time. Facilities with a TBIC focal person were 7.6 times more likely to report any TB cases than facilities without a focal person. Conclusions The TB notification rates among HCW seemed to decrease over time. Availability of PPE increased over the same period. Appointing a TBIC focal person was associated with reporting of TB cases among HCW. It remains unclear whether TBIC measures helped in reduction of the TB notification rates in HCW.

The impact of digital adherence technologies on tuberculosis treatment outcomes remains poorly understood. We investigated whether smart pillboxes and medication labels can reduce poor treatment outcomes in patients with tuberculosis. We did independent pragmatic, cluster-randomised trials in the Philippines, South Africa, Tanzania, and Ukraine. 110 clusters were randomly assigned (1:1) to standard of care versus intervention arms, which were further randomly assigned (1:1; except in Ukraine) to a smart pillbox or medication labels. We enrolled adult patients receiving treatment for drug-susceptible tuberculosis. The pillbox gave an audio-visual reminder to take medication, and when the box was opened, a signal was transmitted to the adherence platform. Those in the labels arm received medications with label attached, showing a code, which they messaged when a dose was taken; otherwise, a reminder was sent. The primary outcome was a composite poor end of treatment outcome, defined as having documented treatment failure, loss to follow-up (treatment interruption for ≥2 consecutive months), switched to a multidrug-resistant regimen more than 28 days after treatment start, or death. The trials are complete and registered with ISRCTN, 17706019. Between June 21, 2021, and July 8, 2022, we enrolled 25 606 individuals (12 626 on standard of care and 12 980 on intervention) across 220 clusters in the four trials, of whom 23 483 (91·7%; 11 313 on standard of care and 12 170 on intervention) were included in the intention-to-treat population. 8208 (35·0%) of 23 483 individuals were female. 9717 (85·9%) of 11 313 individuals in the standard of care arm and 10 540 (86·6%) of 12 170 individuals in the intervention arm were analysed for the primary outcome. The risk of the primary outcome did not differ by intervention arm for all countries (Philippines adjusted odds ratio 1·13, 95% CI 0·72–1·78, p=0·59; Tanzania 1·49, 0·99–2·23; p=0·056; South Africa 1·19, 0·88–1·60; p=0·25; Ukraine adjusted risk ratio 1·15, 95% CI 0·83–1·59; p=0·38). Two incidents of social harm were reported due to inadvertent disclosure of treatment status in the pillbox arm, resulting in withdrawal of the participants. Digital adherence technologies did not reduce poor treatment outcomes in the four countries investigated. The use of digital adherence technologies should be based on careful review of additional data on economic evaluation, patient and stakeholder preferences, and the effect on other important patient outcomes beyond programmatic treatment outcomes. Unitaid.