mHealth application for improving treatment outcomes for patients with multidrug-resistant tuberculosis in Vietnam: an economic evaluation protocol for the V-SMART trial.

INTRODUCTION: The Strengthen the Management of Multidrug-Resistant Tuberculosis in Vietnam (V-SMART) trial is a randomised controlled trial of using mobile health (mHealth) technologies to improve adherence to medications and management of adverse events (AEs) in people with multidrug-resistant tuberculosis (MDR-TB) undergoing treatment in Vietnam. This economic evaluation seeks to quantify the cost-effectiveness of this mHealth intervention from a healthcare provider and societal perspective. METHODS AND ANALYSIS: The V-SMART trial will recruit 902 patients treated for MDR-TB across seven participating provinces in Vietnam. Participants in both intervention and control groups will receive standard community-based therapy for MDR-TB. Participants in the intervention group will also have a purpose-designed App installed on their smartphones to report AEs to health workers and to facilitate timely management of AEs. This economic evaluation will compare the costs and health outcomes between the intervention group (mHealth) and the control group (standard of care). Costs associated with delivering the intervention and health service utilisation will be recorded, as well as patient out-of-pocket costs. The health-related quality of life (HRQoL) of study participants will be captured using the 36-Item Short Form Survey (SF-36) questionnaire and used to calculate quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratios (ICERs) will be based on the primary outcome (proportion of patients with treatment success after 24 months) and QALYs gained. Sensitivity analysis will be conducted to test the robustness of the ICERs. A budget impact analysis will be conducted from a payer perspective to provide an estimate of the total budget required to scale-up delivery of the intervention. ETHICS AND DISSEMINATION: Ethical approval for the study was granted by the University of Sydney Human Research Ethics Committee (2019/676), the Scientific Committee of the Ministry of Science and Technology, Vietnam (08/QD-HDQL-NAFOSTED) and the Institutional Review Board of the National Lung Hospital, Vietnam (13/19/CT-HDDD). Study findings will be published in peer-reviewed journals and conference proceedings. TRIAL REGISTRATION NUMBER: ACTRN12620000681954.

Prioritizing persons deprived of liberty in global guidelines for tuberculosis preventive treatment.

In this Policy Forum piece, Aditya Narayan and colleagues discuss the challenges and opportunities for tuberculosis preventive treatment in carceral settings.

Acceptability of using the medication monitor and experience of a differentiated care approach for TB treatment adherence among people living with TB in South Africa.

BACKGROUND: The introduction of digital adherence technologies (DATs) such as medication monitors in tuberculosis (TB) programmes supports treatment adherence among people with tuberculosis (PWTB). We evaluated the acceptability of using medication monitors (Wisepill evriMED) prompting a stepwise differentiated care approach (DCA), involving short message service (SMS), phone calls, home visits and motivational counselling, among PWTB in South Africa. METHODS: We conducted 62 in-depth interviews with participants in local languages across three provinces (January-October 2020), purposively selected by treatment month, adherence history and gender. Interviews were audio recorded, transcribed verbatim and translated. Using a deductive approach and the Theoretical Framework for Acceptability (TFA), we explored acceptability across the sample attributes. RESULTS: PWTB across adherence histories showed a positive attitude to using the evriMED device and receiving the DCA support. PWTB described the SMS reminders and phone calls as effective reminders, though home visits were less acceptable, due to perceived stigma. Despite willingness to participate in the intervention, the large size of the monitor and sound of the alarm drew attention, potentially causing embarrassment and stigma. Due to perceived stigma, some PWTB adapted the intervention by leaving the monitor at home after removing the pills to ensure that someone else tracked usage, while the PWTB used alternative reminders such as cell phones to take their medication. CONCLUSION: Although PWTB showed a positive attitude towards the intervention, perceived stigma contributed to participants adapting their lifestyle to meet treatment adherence requirements without using the monitor. However, the medication monitor was a tool that seemed to prompt this personal change in behaviour. Achieving people-centered TB care, including the introduction of DATs, will require that TB programmes incorporate PWTB insights to maximize their use and effectiveness.

Smoking behaviour, tobacco sales and tobacco advertising at 40 'Smoke Free Hospitals' in Vietnam.

BACKGROUND: Tobacco remains the leading cause of preventable death globally. Vietnam's 2012 Law on Prevention and Control of Tobacco Harms establishes all healthcare facilities as smoke-free environments. We aimed to evaluate the implementation of these policies within health facilities across Vietnam. METHODS: A cross-sectional study was undertaken at 40 central, provincial, district and commune healthcare facilities in four provinces of Vietnam. The presence of tobacco sales, smoke-free signage, evidence of recent tobacco use and smoking behaviours by patients and staff were observed over a 1-week period at multiple locations within each facility. Adherence with national regulations was reported using descriptive statistics. RESULTS: 23 out of 40 facilities (57.5%) followed the requirements of the national smoke-free policy regarding tobacco sales, advertising and signage. Smoking was observed within health facility grounds at 26 (65%) facilities during the observation period. Indirect evidence of smoking was observed at 35 (88%) facilities. Sites where smoking was permitted (n=2) were more likely to have observed smoking behaviour (relative risk (RR) 2.16, 95% CI 1.83 to 2.56). Facilities where tobacco was sold (n=7) were more likely to have smoking behaviour observed at any of their sites (RR 1.53, 95% CI 0.93 to 2.51). CONCLUSIONS: Implementation of current smoke-free hospital regulations remains incomplete, with widespread evidence of smoking observed at three levels of the Vietnamese healthcare facilities. Further interventions are required to establish the reputation of Vietnamese healthcare facilities as smoke-free environments.

Human resource time commitments and associated costs of Community Caregiver outreach team operations in South Africa.

INTRODUCTION: In South Africa, Community Caregivers (CCGs) visit households to provide basic healthcare services including those for tuberculosis and HIV. However, CCG workloads, costs, and time burden are largely unknown. Our objective was to assess the workloads and operational costs for CCG teams operating in different settings in South Africa. METHODS: Between March and October 2018, we collected standardized self-reported activity time forms from 11 CCG pairs working at two public health clinics in Ekurhuleni district, South Africa. CCG workloads were assessed based on activity unit times, per-household visit time, and mean daily number of successful household visits. Using activity-based times and CCG operating cost data, we assessed CCG annual and per-household visit costs (USD 2019) from the health system perspective. RESULTS: CCGs in clinic 1 (peri-urban, 7 CCG pairs) and 2 (urban, informal settlement; 4 CCG pairs) served an area of 3.1 km2 and 0.6 km2 with 8,035 and 5,200 registered households, respectively. CCG pairs spent a median 236 minutes per day conducting field activities at clinic 1 versus 235 minutes at clinic 2. CCG pairs at clinic 1 spent 49.5% of this time at households (versus traveling), compared to 35.0% at clinic 2. On average, CCG pairs successfully visited 9.5 vs 6.7 households per day for clinics 1 and 2, respectively. At clinic 1, 2.7% of household visits were unsuccessful, versus 28.5% at clinic 2. Total annual operating costs were higher in clinic 1 ($71,780 vs $49,097) but cost per successful visit was lower ($3.58) than clinic 2 ($5.85). CONCLUSIONS: CCG home visits were more frequent, successful, and less costly in clinic 1, which served a larger and more formalized settlement. The variability in workload and cost observed across pairs and clinics suggests that circumstantial factors and CCG needs must be carefully assessed for optimized CCG outreach operations.

Qualitative study exploring the feasibility of using medication monitors and a differentiated care approach to support adherence among people receiving TB treatment in South Africa.

OBJECTIVES: The tuberculosis (TB) MATE study evaluated whether a differentiated care approach (DCA) based on tablet-taking data from Wisepill evriMED digital adherence technology could improve TB treatment adherence. The DCA entailed a stepwise increase in adherence support starting from short message service (SMS) to phone calls, followed by home visits and motivational counselling. We explored feasibility of this approach with providers in implementing clinics. DESIGN: Between June 2020 and February 2021, in-depth interviews were conducted in the provider's preferred language, audiorecorded, transcribed verbatim and translated. The interview guide included three categories: feasibility, system-level challenges and sustainability of the intervention. We assessed saturation and used thematic analysis. SETTING: Primary healthcare clinics in three provinces of South Africa. PARTICIPANTS: We conducted 25 interviews with 18 staff and 7 stakeholders. RESULTS: Three major themes emerged: First, providers were supportive of the intervention being integrated into the TB programme and were eager to be trained on the device as it helped to monitor treatment adherence. Second, there were challenges in the adoption system such as shortage of human resources which could serve as a barrier to information provision once the intervention is scaled up. Healthcare workers reported that some patients received incorrect SMS's due to delays in the system that contributed to distrust. Third, DCA was considered as a key aspect of the intervention by some staff and stakeholders since it allowed for support based on individual needs. CONCLUSIONS: It was feasible to monitor TB treatment adherence using the evriMED device and DCA. To ensure successful scale-up of the adherence support system, emphasis will need to be placed on ensuring that the device and the network operate optimally and continued support on adhering to treatment which will enable people with TB to take ownership of their treatment journey and help overcome TB-related stigma. TRIAL REGISTRATION NUMBER: Pan African Trial Registry PACTR201902681157721.

A qualitative exploration into the presence of TB stigmatization across three districts in South Africa.

BACKGROUND: Tuberculosis (TB) stigma is a barrier to active case finding and delivery of care in fighting the TB epidemic. As part of a project exploring different models for delivery of TB contact tracing, we conducted a qualitative analysis to explore the presence of TB stigma within communities across South Africa. METHODS: We conducted 43 in-depth interviews with 31 people with TB and 12 household contacts as well as five focus group discussions with 40 ward-based team members and 11 community stakeholders across three South African districts. RESULTS: TB stigma is driven and facilitated by fear of disease coupled with an understanding of TB/HIV duality and manifests as anticipated and internalized stigma. Individuals are marked with TB stigma verbally through gossip and visually through symptomatic identification or when accessing care in either TB-specific areas in health clinics or though ward-based outreach teams. Individuals' unique understanding of stigma influences how they seek care. CONCLUSION: TB stigma contributes to suboptimal case finding and care at the community level in South Africa. Interventions to combat stigma, such as community and individual education campaigns on TB treatment and transmission as well as the training of health care workers on stigma and stigmatization are needed to prevent discrimination and protect patient confidentiality.

Scaling up evidence-based approaches to tuberculosis screening in prisons.

People deprived of liberty have among the highest rates of tuberculosis globally. The incidence of tuberculosis is ten times greater than the incidence of tuberculosis in the general population. In 2021, WHO updated its guidance to strongly recommend systematic screening for tuberculosis in prisons and penitentiary systems. Which case-finding strategies should be adopted, and how to effectively implement these strategies in these settings, will be crucial questions facing ministries of health and justice. In this Viewpoint, we review the evidence base for tuberculosis screening and diagnostic strategies in prisons, highlighting promising approaches and knowledge gaps. Drawing upon past experiences of implementing active case-finding and care programmes in settings with a high tuberculosis burden, we discuss challenges and opportunities for improving the tuberculosis diagnosis and treatment cascade in these settings. We argue that improved transparency in reporting of tuberculosis notifications and outcomes in prisons and renewed focus and resourcing from WHO and other stakeholders will be crucial for building the commitment and investments needed from countries to address the continued crisis of tuberculosis in prisons.

Designing molecular diagnostics for current tuberculosis drug regimens.

Diagnostic development must occur in parallel with drug development to ensure the longevity of new treatment compounds. Despite an increasing number of novel and repurposed anti-tuberculosis compounds and regimens, there remains a large number of drugs for which no rapid and accurate molecular diagnostic option exists. The lack of rapid drug susceptibility testing for linezolid, bedaquiline, clofazimine, the nitroimidazoles (i.e pretomanid and delamanid) and pyrazinamide at any level of the healthcare system compromises the effectiveness of current tuberculosis and drug-resistant tuberculosis treatment regimens. In the context of current WHO tuberculosis treatment guidelines as well as promising new regimens, we identify the key diagnostic gaps for initial and follow-on tests to diagnose emerging drug resistance and aid in regimen selection. Additionally, we comment on potential gene targets for inclusion in rapid molecular drug susceptibility assays and sequencing assays for novel and repurposed drug compounds currently prioritized in current regimens, and evaluate the feasibility of mutation detection given the design of existing technologies. Based on current knowledge, we also propose design priorities for next generation molecular assays to support triage of tuberculosis patients to appropriate and effective treatment regimens. We encourage assay developers to prioritize development of these key molecular assays and support the continued evolution, uptake, and utility of sequencing to build knowledge of tuberculosis resistance mechanisms and further inform rapid treatment decisions in order to curb resistance to critical drugs in current regimens and achieve End TB targets.Trial registration: ClinicalTrials.gov identifier: NCT05117788..

Preventive Treatment for Household Contacts of Drug-Susceptible Tuberculosis Patients.

People who live in the household of someone with infectious pulmonary tuberculosis are at a high risk of tuberculosis infection and subsequent progression to tuberculosis disease. These individuals are prioritized for contact investigation and tuberculosis preventive treatment (TPT). The treatment of TB infection is critical to prevent the progression of infection to disease and is prioritized in household contacts. Despite the availability of TPT, uptake in household contacts is poor. Multiple barriers prevent the optimal implementation of these policies. This manuscript lays out potential next steps for closing the policy-to-implementation gap in household contacts of all ages.

Monocyte Transcriptional Responses to Mycobacterium tuberculosis Associate with Resistance to Tuberculin Skin Test and Interferon Gamma Release Assay Conversion.

Heavy exposure to Mycobacterium tuberculosis, the etiologic agent of tuberculosis (TB) and among the top infectious killers worldwide, results in infection that is cleared, contained, or progresses to disease. Some heavily exposed tuberculosis contacts show no evidence of infection using the tuberculin skin test (TST) and interferon gamma release assay (IGRA); yet the mechanisms underlying this "resister" (RSTR) phenotype are unclear. To identify transcriptional responses that distinguish RSTR monocytes, we performed transcriptome sequencing (RNA-seq) on monocytes isolated from heavily exposed household contacts in Uganda and gold miners in South Africa after ex vivo M. tuberculosis infection. Gene set enrichment analysis (GSEA) revealed several gene pathways that were consistently enriched in response to M. tuberculosis among RSTR subjects compared to controls with positive TST/IGRA testing (latent TB infection [LTBI]) across Uganda and South Africa. The most significantly enriched gene set in which expression was increased in RSTR relative to LTBI M. tuberculosis-infected monocytes was the tumor necrosis factor alpha (TNF-α) signaling pathway whose core enrichment (leading edge) substantially overlapped across RSTR populations. These leading-edge genes included candidate resistance genes (ABCA1 and DUSP2) with significantly increased expression among Uganda RSTRs (false-discovery rate [FDR], <0.1). The distinct monocyte transcriptional response to M. tuberculosis among RSTR subjects, including increased expression of the TNF signaling pathway, highlights genes and inflammatory pathways that may mediate resistance to TST/IGRA conversion and provides therapeutic targets to enhance host restriction of M. tuberculosis intracellular infection. IMPORTANCE After heavy M. tuberculosis exposure, the events that determine why some individuals resist TST/IGRA conversion are poorly defined. Enrichment of the TNF signaling gene set among RSTR monocytes from multiple distinct cohorts suggests an important role for the monocyte TNF response in determining this alternative immune outcome. These TNF responses to M. tuberculosis among RSTRs may contribute to antimicrobial programs that result in early clearance or the priming of alternative (gamma interferon-independent) cellular responses.

Harnessing new mHealth technologies to Strengthen the Management of Multidrug-Resistant Tuberculosis in Vietnam (V-SMART trial): a protocol for a randomised controlled trial.

INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) remains a major public health problem globally. Long, complex treatment regimens coupled with frequent adverse events have resulted in poor treatment adherence and patient outcomes. Smartphone-based mobile health (mHealth) technologies offer national TB programmes an appealing platform to improve patient care and management; however, clinical trial evidence to support their use is lacking. This trial will test the hypothesis that an mHealth intervention can improve treatment success among patients with MDR-TB and is cost-effective compared with standard practice. METHODS AND ANALYSIS: A community-based, open-label, parallel-group randomised controlled trial will be conducted among patients treated for MDR-TB in seven provinces of Vietnam. Patients commencing therapy for microbiologically confirmed rifampicin-resistant or multidrug-resistant tuberculosis within the past 30 days will be recruited to the study. Participants will be individually randomised to an intervention arm, comprising use of an mHealth application for treatment support, or a 'standard care' arm. In both arms, patients will be managed by the national TB programme according to current national treatment guidelines. The primary outcome measure of effectiveness will be the proportion of patients with treatment success (defined as treatment completion and/or bacteriological cure) after 24 months. A marginal Poisson regression model estimated via a generalised estimating equation will be used to test the effect of the intervention on treatment success. A prospective microcosting of the intervention and within-trial cost-effectiveness analysis will also be undertaken from a societal perspective. Cost-effectiveness will be presented as an incremental cost per patient successfully treated and an incremental cost per quality-adjusted life-year gained. ETHICS: Ethical approval for the study was granted by The University of Sydney Human Research Ethics Committee (2019/676). DISSEMINATION: Study findings will be disseminated to participants and published in peer-reviewed journals and conference proceedings. TRIAL REGISTRATION NUMBER: ACTRN12620000681954.

Resistance to Mycobacterium tuberculosis infection among highly TB exposed South African gold miners.

BACKGROUND: Despite high exposure to Mycobacterium tuberculosis, a small proportion of South African goldminers resist TB infection. We determined, among long-service gold miners i) the proportion who were TB uninfected and ii) epidemiological factors associated with being uninfected. METHODS: We enrolled HIV-negative gold miners aged 33-60 years with ≥15 years' service and no history of TB or silicosis. Miners were defined as TB uninfected if i) QuantiFERON-TB Gold Plus (QFT-Plus) negative or ii) in a stricter definition, QFT-Plus-negative and zero-response on TST and as resisters if they were of Black/African ethnicity and negative on both tests. Logistic regression was used to identify epidemiological factors associated with being TB uninfected. RESULTS: Of 307 participants with a QFT-Plus result, median age was 48 years (interquartile range [IQR] 44-53), median time working underground was 24 years (IQR 18-28), 303 (99%) were male and 91 (30%) were QFT-Plus-negative. The odds of being TB uninfected was 52% lower for unskilled workers (adjusted odds ratio [aOR] 0.48; 95% confidence interval [CI] 0.27-0.85; p = 0.013). Among 281 participants of Black/African ethnicity, 71 (25%) were QFT-Plus negative. Miners with a BMI ≥30 were less likely to be TB uninfected (OR 0.38; 95% CI 0.18-0.80). Using the stricter definition, 44.3% (136/307) of all miners were classified as either TB uninfected (35; 26%) or infected, (101; 74%) and the associations remained similar. Among Black/African miners; 123 were classified as either TB uninfected (23; 19%) or infected (100; 81%) using the stricter definition. No epidemiological factors for being TB uninfected were identified. CONCLUSIONS: Despite high cumulative exposure, a small proportion of miners appear to be resistant to TB infection and are without distinguishing epidemiological characteristics.

Predictors of treatment outcomes among patients with multidrug-resistant tuberculosis in Vietnam: a retrospective cohort study.

BACKGROUND: Improving treatment outcomes for multidrug-resistant tuberculosis (MDR-TB) is a leading priority for global TB control. This retrospective cohort study evaluated the factors associated with treatment success among patients treated for MDR-TB in two provinces in Vietnam. METHODS: Treatment outcomes were evaluated for adult patients treated in Hanoi and Thanh Hoa provinces between 2014 and 2016. The primary outcome was the proportion of patients with treatment success, defined as cure or treatment completion. Logistic regression analysis was used to evaluate the relationship between patient clinical and microbiological characteristics and treatment success. RESULTS: Treatment outcomes were reported in 612 of 662 patients; of these, 401 (65.5)% were successfully treated. The odds of treatment success were lower for male patients (aOR 0.56, 95% CI 0.34-0.90), for people living with HIV (aOR 0.44, 95% CI 0.20-1.00), and for patients treated for extensive antibiotic resistance (pre-XDR-/XDT-TB) (aOR 0.53, 95% CI 0.29-0.97), compared with others. Patients who achieved culture conversion in the first 4 months of treatment had increased odds (aOR 2.93, 95% CI 1.33-6.45) of treatment success. In addition, loss to follow-up was less common among patients covered by social health insurance compared to those who paid for treatment out-of-pocket (aOR 0.55, 95% CI 0.32-0.95). CONCLUSIONS: Among patients with MDR-TB, males, people living with HIV, and those with more extensive antibiotic resistance at diagnosis are at greatest risk of an unsuccessful treatment outcome. Efforts to optimise the management of co-morbidities (such as HIV), ensure rapid bacteriological conversion, and provide financial support for patients promise to improve treatment outcomes.

Digital Chest Radiography Enhances Screening Efficiency for Pulmonary Tuberculosis in Primary Health Clinics in South Africa.

BACKGROUND: Optimized tuberculosis (TB) screening in high burden settings is essential for case finding. We evaluated digital chest X-ray with computer-aided detection (CAD) software (d-CXR) for identifying undiagnosed TB in three primary health clinics in South Africa. METHODS: The cross-sectional study consented adults who were sequentially screened for TB using the World Health Organization (WHO) 4 symptom questionnaire and d-CXR. Participants reporting ≥1 TB symptom and/or CAD score ≥60 (suggestive of TB) provided 2 spot sputum for Xpert MTB/RIF Ultra (Xpert Ultra) and liquid culture testing, respectively. TB yield (proportion of screened tested positive) and number needed to test (NNT; no of tests to identify one TB patient) were calculated. Risk factors for microbiologically confirmed or presumed (on radiological grounds) were determined. RESULTS: Among 3041 participants, 45% (1356 of 3041) screened positive on either d-CXR or symptoms. TB yield was 2.3% (71 of 3041) using Xpert Ultra and 2.7% (82 of 3041) using Xpert Ultra plus culture. Modelled TB yield (identified by Xpert Ultra) by screening approach was: 1.9% (59 of 3041) for d-CXR alone, 2.0% (62 of 3041) for symptoms alone and 2.3% (71 of 3041) for both. The NNT was 9.7 for d-CXR, 17.8 for symptoms and 19.1 for d-CXR and/or symptom. Males, those with previous TB, untreated HIV or unknown HIV status, and acute illness were at higher risk of developing TB. CONCLUSION: d-CXR screening identified a similar yield of undiagnosed TB compared to symptom-based screening, however required fewer diagnostic tests. Due to its objective nature, d-CXR screening may improve case detection in clinics.

Digital Chest X-Ray with Computer-aided Detection for Tuberculosis Screening within Correctional Facilities.

Rationale: Realizing the Global Plan to End Tuberculosis (TB) will require reaching at least 90% of people in key populations, such as inmates, through optimizing case-finding approaches. Objectives: To evaluate the value of adding digital chest X-ray (d-CXR) with computer-aided detection (CAD) to symptom-based screening on TB yield among inmates. Methods: Consecutive adult inmates from four correctional facilities in South Africa were screened for TB using symptoms and d-CXR. Any person with at least one symptom or CAD score of ⩾50 provided two sputa for liquid culture and GeneXpert MTB/RIF Ultra (Xpert Ultra) testing. In a sample of 800 symptom-negative inmates with CAD score <50, Xpert Ultra testing was also conducted. TB yield was defined as the proportion of new patients with bacteriologically confirmed TB who were identified. Results: We enrolled 3,576 participants: 99.6% male, median age of 34 years (interquartile range, 28-41), and 584 (16.3%) with positive test results for human immunodeficiency virus. Of those screened, 867 (24.2%) participants required investigation (394 [11.2%] symptomatic, 685 [19.1%] with abnormal CAD results, and 867 [24.2%] with either). Sputum was taken in 747 (86.2%) participants, with 28 (7.8 per 1,000 population) new TB cases diagnosed. On the basis of hypothesized screening modalities, yield would have been 3.6 per 1,000 population on the basis of symptoms alone and 7.0 per 1,000 population on the basis of d-CXR alone. Among an additional 800 inmates tested who initially screened symptom negative and had a CAD score <50, five TB cases were diagnosed. There was no difference in TB yield when comparing Xpert Ultra against culture (5.6 vs. 4.8 per 1,000 population; P = 0.21). Conclusions: The addition of d-CXR identified two times more patients with undiagnosed TB than did investigation of symptoms alone. Complementary use of d-CXR may potentially overcome the subjectivity inherent in symptom screening alone for identifying TB in this population.

Standardised patient study to assess tuberculosis case detection within the private pharmacy sector in Vietnam.

BACKGROUND: Of the estimated 10 million people affected by (TB) each year, one-third are never diagnosed. Delayed case detection within the private healthcare sector has been identified as a particular problem in some settings, leading to considerable morbidity, mortality and community transmission. Using unannounced standardised patient (SP) visits to the pharmacies, we aimed to evaluate the performance of private pharmacies in the detection and treatment of TB. METHODS: A cross-sectional study was undertaken at randomly selected private pharmacies within 40 districts of Vietnam. Trained actors implemented two standardised clinical scenarios of presumptive TB and presumptive multidrug-resistant TB (MDR-TB). Outcomes were the proportion of SPs referred for medical assessment and the proportion inappropriately receiving broad-spectrum antibiotics. Logistic regression evaluated predictors of SPs' referral. RESULTS: In total, 638 SP encounters were conducted, of which only 155 (24.3%) were referred for medical assessment; 511 (80·1%) were inappropriately offered antibiotics. A higher proportion of SPs were referred without having been given antibiotics if they had presumptive MDR-TB (68/320, 21.3%) versus presumptive TB (17/318, 5.3%; adjusted OR=4.8, 95% CI 2.9 to 7.8). Pharmacies offered antibiotics without a prescription to 89.9% of SPs with presumptive TB and 70.3% with presumptive MDR-TB, with no clear follow-up plan. CONCLUSIONS: Few SPs with presumptive TB were appropriately referred for medical assessment by private pharmacies. Interventions to improve appropriate TB referral within the private pharmacy sector are urgently required to reduce the number of undiagnosed TB cases in Vietnam and similar high-prevalence settings.

Latent tuberculosis infection among contacts of patients with multidrug-resistant tuberculosis in New South Wales, Australia.

BACKGROUND: Contacts of an individual with active tuberculosis (TB) disease have a higher risk of developing latent TB infection (LTBI) or active TB disease. Contact tracing is a public health measure that seeks to identify exposed contacts, screen them for co-prevalent TB and consider prophylactic treatment to prevent progression from LTBI to active TB disease. The investigators sought to determine the prevalence of LTBI and active TB disease among contacts of patients with multidrug-resistant (MDR)-TB in New South Wales, Australia. METHODOLOGY: A retrospective cohort study was performed among the contacts of patients diagnosed with MDR-TB between 2000 and 2016, inclusive, at seven chest clinics. Medical records were used to identify eligible contacts. Outcomes of screening and prophylactic treatment regimens offered to MDR-TB contacts with LTBI were characterised. Collected data included demographic information, screening tests results and initial management. RESULTS: In total, 247 contacts of 55 MDR-TB patients were identified. LTBI was identified in 105 contacts (42.5%). Preventive treatment was received by 20 contacts with LTBI (32.3%) in the form of various regimens, ranging from one to three antimicrobials, with various doses and durations. One contact with LTBI who was untreated progressed to active TB disease during the study period, according to clinic notes. CONCLUSION: Contacts of MDR-TB patients have a high prevalence of LTBI. Management of these contacts varies substantially in New South Wales, reflecting a lack of definitive evidence for preventive therapy. Further research is required to determine the optimal management of this population.

Exploring the promise and reality of ward-based primary healthcare outreach teams conducting TB household contact tracing in three districts of South Africa.

BACKGROUND: Tuberculosis (TB) household contact tracing is a form of targeted active case-finding for which community health workers ('outreach teams') in South Africa are primarily responsible for its implementation. We conducted an exploratory qualitative study to understand the role of outreach teams in delivering TB household contact tracing. METHODS: The study took place in three districts of South Africa between May 2016 and February 2017. We conducted 78 in-depth interviews (IDI) (comprising 35 key stakeholders, 31 TB index patients and 12 HHCs) and five focus group discussions (FGD) (40 outreach team members in four FGDs and 12 community stakeholders in one FGD). RESULTS: Outreach teams contributed positively by working across health-related programmes, providing home-based care and assisting with tracing of persons lost to TB care. However, outreach teams had a limited focus on TB household contact tracing activities, likely due to the broad scope of their work and insufficient programmatic support. Outreach teams often confused TB household contact tracing activities with finding persons lost to TB care. The community also had some reservations on the role of outreach teams conducting TB household contact tracing activities. CONCLUSIONS: Creating awareness among outreach workers and clinic personnel about the importance of and activities related to TB household contact tracing would be required to strengthen the delivery of TB household contact tracing through the community-based primary health care teams. We need better monitoring and evaluation systems, stronger integration within a realistic scope of work, adequate training on TB household contact tracing and TB infection prevention control measures. Involving the community and educating them on the role of outreach teams could improve acceptance of future activities. These timely results and lessons learned should inform contact tracing approaches in the context of COVID-19.

Individualised treatment for multidrug-resistant tuberculosis in New South Wales, Australia.

OBJECTIVE: Multidrug-resistant tuberculosis (MDR-TB) presents a major global health challenge. In high-income countries, treatment is individualised to optimise efficacy and reduce toxicity. We aimed to evaluate the outcomes of patients with MDR-TB receiving individualised antibiotic therapy in Australia. METHODS: This retrospective cohort study was performed in the city of Sydney in Australia and included patients diagnosed with bacteriologically confirmed MDR-TB diagnosed between 2000 and 2016. The clinical characteristics of patients and treatment details were extracted from medical records. The incidence of adverse events and end-of-treatment outcomes were also evaluated. RESULTS: Fifty-five patients with MDR-TB were identified at TB clinics in seven hospitals. The median age was 32 years (interquartile range [IQR]: 27-36 years). The median duration of the intensive phase treatment was six months (IQR 6-7 months). All patients' treatment administration was directly observed. The commonest reported adverse event was ototoxicity (44%; 23/52) and successful treatment outcomes were achieved by 95% (52/55) of patients. CONCLUSION: This study demonstrated the high treatment success rate that can be achieved using individualised treatment for MDR-TB in a well-resourced setting. Implications for public health: The expansion of individualised therapy promises to contribute to MDR-TB control and advance the ambitious goal of TB elimination by 2035.