Retrospective Cohort Study of Effects of the COVID-19 Pandemic on Tuberculosis Notifications, Vietnam, 2020.

We evaluated the effects of the coronavirus disease pandemic on diagnosis of and treatment for tuberculosis (TB) in Vietnam. We obtained quarterly notifications for TB and multidrug-resistant/rifampin-resistant (MDR/RR) TB from 2015-2020 and evaluated changes in monthly TB case notifications. We used an interrupted time series to assess the change in notifications and treatment outcomes. Overall, TB case notifications were 8% lower in 2020 than in 2019; MDR/RR TB notifications were 1% lower. TB case notifications decreased by 364 (95% CI -1,236 to 508) notifications per quarter and MDR/RR TB by 1 (95% CI -129 to 132) notification per quarter. The proportion of successful TB treatment outcomes decreased by 0.1% per quarter (95% CI -1.1% to 0.8%) in 2020 compared with previous years. Our study suggests that Vietnam was able to maintain its TB response in 2020, despite the pandemic.

Community-wide Screening for Tuberculosis in a High-Prevalence Setting.

BACKGROUND: The World Health Organization has set ambitious targets for the global elimination of tuberculosis. However, these targets will not be achieved at the current rate of progress. METHODS: We performed a cluster-randomized, controlled trial in Ca Mau Province, Vietnam, to evaluate the effectiveness of active community-wide screening, as compared with standard passive case detection alone, for reducing the prevalence of tuberculosis. Persons 15 years of age or older who resided in 60 intervention clusters (subcommunes) were screened for pulmonary tuberculosis, regardless of symptoms, annually for 3 years, beginning in 2014, by means of rapid nucleic acid amplification testing of spontaneously expectorated sputum samples. Active screening was not performed in the 60 control clusters in the first 3 years. The primary outcome, measured in the fourth year, was the prevalence of microbiologically confirmed pulmonary tuberculosis among persons 15 years of age or older. The secondary outcome was the prevalence of tuberculosis infection, as assessed by an interferon gamma release assay in the fourth year, among children born in 2012. RESULTS: In the fourth-year prevalence survey, we tested 42,150 participants in the intervention group and 41,680 participants in the control group. A total of 53 participants in the intervention group (126 per 100,000 population) and 94 participants in the control group (226 per 100,000) had pulmonary tuberculosis, as confirmed by a positive nucleic acid amplification test for Mycobacterium tuberculosis (prevalence ratio, 0.56; 95% confidence interval [CI], 0.40 to 0.78; P<0.001). The prevalence of tuberculosis infection in children born in 2012 was 3.3% in the intervention group and 2.6% in the control group (prevalence ratio, 1.29; 95% CI, 0.70 to 2.36; P = 0.42). CONCLUSIONS: Three years of community-wide screening in persons 15 years of age or older who resided in Ca Mau Province, Vietnam, resulted in a lower prevalence of pulmonary tuberculosis in the fourth year than standard passive case detection alone. (Funded by the Australian National Health and Medical Research Council; ACT3 Australian New Zealand Clinical Trials Registry number, ACTRN12614000372684.).

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.

A smoking quitline integrated with clinician counselling at outpatient health facilities in Vietnam: a single-arm prospective cohort study.

BACKGROUND: Limited evidence is available about the combination of multiple smoking cessation modalities in low- and middle-income countries. The study aimed to assess the feasibility of a smoking cessation intervention that integrates follow-up counselling phone calls and scheduled text messages with brief advice from physicians in Vietnam. METHODS: This was a single-arm intervention study. Smokers were referred to the study Quitline after brief advice by physicians at three rural district hospitals in Hanoi, Vietnam. Following referral, participants received nine counselling phone calls in 12 months and a scheduled text message service that lasted for three months. Participants who reported smoking cessation for at least 30 days at the 12-month follow-up were invited for a urinary cotinine test to confirm cessation. RESULTS: The Quitline centre had 431 referrals from participating hospitals. Among them, 221 (51.3%) were enrolled. After the baseline phone call, 141 (63.8%) participated in all 4 follow-up calls within the first month and 117 (52.9%) participated in all phone calls in 12 months. The median number of successful phone calls was 8 (interquartile range: 6 - 8). At the end of the study, 90 (40.7%) self-reported abstinence from smoking over the previous 30 days. Among them, 22 (24.4%) submitted a sample for cotinine test, of which 13 (59.1% of those tested) returned a negative result. The proportion of biochemically-verified quitters was 5.9%. CONCLUSIONS: The integration of brief advice and referral from healthcare facilities, Quitline counselling phone calls, and scheduled text messaging was feasible in rural health facilities in northern Vietnam. TRIAL REGISTRATION: ACTRN12619000554167 .

Azole-resistant Aspergillus fumigatus is highly prevalent in the environment of Vietnam, with marked variability by land use type.

Azole-resistant environmental Aspergillus fumigatus presents a threat to public health but the extent of this threat in Southeast Asia is poorly described. We conducted environmental surveillance in the Mekong Delta region of Vietnam, collecting air and ground samples across key land-use types, and determined antifungal susceptibilities of Aspergillus section Fumigati (ASF) isolates and azole concentrations in soils. Of 119 ASF isolates, 55% were resistant (or non-wild type) to itraconazole, 65% to posaconazole and 50% to voriconazole. Azole resistance was more frequent in A. fumigatus sensu stricto isolates (95%) than other ASF species (32%). Resistant isolates and agricultural azole residues were overrepresented in samples from cultivated land. cyp51A gene sequence analysis showed 38/56 resistant A. fumigatus sensu stricto isolates carried known resistance mutations, with TR34 /L98H most frequent (34/38).

What are the most effective community-based antimicrobial stewardship interventions in low- and middle-income countries? A narrative review.

Antimicrobial resistance (AMR) is a major global issue and antimicrobial stewardship is central to tackling its emergence. The burden of AMR disproportionately impacts low- and middle-income countries (LMICs), where capacity for surveillance and management of resistant pathogens is least developed. Poorly regulated antibiotic consumption in the community is a major driver of AMR, especially in LMICs, yet community-based interventions are neglected in stewardship research, which is often undertaken in high-income settings and/or in hospitals. We reviewed the evidence available to researchers and policymakers testing or implementing community-based antimicrobial stewardship strategies in LMICs. We critically appraise that evidence, deliver recommendations and identify outstanding areas of research need. We find that multifaceted, education-focused interventions are likely most effective in our setting. We also confirm that the quality and quantity of community-based stewardship intervention research is limited, with research on microbiological, clinical and economic sustainability most urgently needed.

Factors affecting healthcare pathways for chronic lung disease management in Vietnam: a qualitative study on patients' perspectives.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma rank among the leading causes of respiratory morbidity, particularly in low- and middle-income countries. This qualitative study aimed to explore the healthcare pathways of patients with chronic respiratory disease, and factors influencing their ability to access healthcare in Vietnam, where COPD and asthma are prevalent. METHODS: We conducted 41 in-depth interviews among patients, including 31 people with COPD, eight with asthma and two with asthma-COPD overlap syndrome. Participants were recruited at provincial- or national-level health facilities in two urban and two rural provinces in Vietnam. The interviews were audio-recorded, transcribed, and analysed using thematic analysis. RESULTS: Patients' healthcare pathways were complex and involved visits to multiple health facilities before finally obtaining a definitive diagnosis at a provincial- or national-level hospital. Access to healthcare was affected considerably by participants' limited knowledge of their respiratory conditions, the availability of social support, especially from family members, the costs of healthcare as well as health system factors (including the coverage of public health insurance, the distance to health facilities, and attitude of healthcare providers). CONCLUSION: The study demonstrated the need for improved access to timely diagnosis and treatment of chronic lung disease within the lower level of the health system. This can be achieved by enhancing the communication skills and diagnostic capacity of local healthcare workers. Health education programmes for patients and caregivers will contribute to improved control of lung disease.

Smoking behaviour among adult patients presenting to health facilities in four provinces of Vietnam.

BACKGROUND: Attendance at healthcare facilities provides an opportunity for smoking cessation interventions. However, the smoking behaviours of patients seeking healthcare in Vietnam are not well-understood. We aimed to evaluate behaviours related to smoking among patients presenting to health facilities in Vietnam. METHODS: We conducted a cross-sectional study in 4 provinces of Vietnam. Consecutive patients aged ≥15 years presenting to 46 health facilities were assessed. Current smokers were randomly selected to complete a full survey about smoking behaviour, quit attempts, and preparedness to quit. RESULTS: Among 11,245 patients who sought healthcare, the prevalence of current smoking was 18.6% (95% CI: 17.8-19.4%) overall, 34.6% (95% CI: 33.2-36.0%) among men and 1.1% (95% CI: 0.8-1.3%) among women. Current smokers who were asked about smoking by healthcare providers in the last 12 months were more likely to make quit attempts than those not asked (40.6% vs 31.8%, p = 0.017). Current smokers who attempted to quit in the past 12 months made limited use of cessation aids: counselling (1.9%) and nicotine replacement therapy (10%). A higher proportion of patients wanted to quit in the next month at national/provincial hospitals (30.3%) than those visiting district hospitals (11.3%, p < 0.001) and commune health centres (11.1%, p = 0.004). CONCLUSIONS: Smoking is common among male patients presenting to healthcare facilities in Vietnam. Formal smoking cessation supports are generally not used or offered. This population is likely to benefit from routine smoking cessation interventions that are integrated within the routine healthcare delivery system.

Active contact tracing beyond the household in multidrug resistant tuberculosis in Vietnam: a cohort study.

BACKGROUND: Currently in Vietnam contact tracing for multidrug-resistant tuberculosis (MDR-TB) entails passive case finding among symptomatic household contacts who present themselves for diagnosis. Close contacts of MDR-TB cases are therefore not identified adequately. We assessed the added value of active contact tracing within and beyond households using social network questionnaires to identify close contacts of MDR-TB patients in Vietnam. METHODS: We conducted a cohort study using social network questionnaires in which contacts were identified by MDR-TB patients, including contacts from 'high risk' places like work. Contacts of MDR-TB patients were followed up and screened over a period of at least 6 months. This included two active screenings and any unscheduled passive screening of self-referred contacts during the study period. RESULTS: Four hundred seventeen contacts of 99 index cases were recruited, 325 (77.9%) and 160/417 (38.4%) contacts participated in the first and second screenings, respectively. The first screening detected one TB case but the bacteria were not MDR. From passive screening, a household contact was diagnosed with TB meningitis but not through our active approach. Social network analysis showed that only 1/17 (5.9%) high-risk places agreed to cooperate and were included in the screening, and no MDR-TB cases were detected. There were two pairs of index cases (identified separately) who were found to be contacts of each other and who had been diagnosed before the study started. CONCLUSIONS: No new MDR-TB cases were detected using social network analysis of nearly 100 MDR-TB index cases, likely due to a relatively short follow up time, and loss to follow up (lack of cooperation from contacts or high risk places and lack of available resources in the National Tuberculosis Control Programme).

Asia-Pacific Colorectal Screening score: A useful tool to stratify risk for colorectal advanced neoplasms in Vietnamese patients with irritable bowel syndrome.

BACKGROUND AND AIM: The Asia-Pacific Colorectal Screening (APCS) score has been validated in several populations but not yet in patients with irritable bowel syndrome (IBS). The aim of this study was to assess the performance of APCS score in stratifying risk of colorectal advanced neoplasms (CAN) in Vietnamese IBS patients. METHODS: Consecutive patients who fulfilled IBS diagnosis criteria according to the Rome III were prospectively enrolled and underwent colonoscopy. APCS score for each patient was calculated by summing the points attributed by risk factors. Three tiers of risk were defined: 0-1 "average risk" (AR); 2-3 "moderate risk" (MR); and 4-7 "high risk" (HR). Logistic regression analysis was performed to assess the relative risk of CAN in HR group and MR group compared with AR group. RESULTS: There were 404 patients with excellent bowel preparation and complete colonoscopy. The mean age was 48.8 ± 11.2 years and male : female ratio was 1.2:1. Twenty-eight patients (6.9%) were diagnosed with CAN: 19 (4.7%) advanced adenoma and 9 (2.2%) invasive colorectal cancer. Patients in the MR and HR tiers had 5.6-fold (95% confidence interval 1.2 to 24.7, P = 0.012) and 12.1-fold (95% confidence interval 2.6 to 56.2, P < 0.001) increased rates of CAN compared with those in the AR tier, respectively. Three out of 9 patients with invasive colorectal cancer had no alarm features but had high sum APCS score (2 in MR tier and 1 in HR tier). CONCLUSION: The APCS score is useful to identify IBS patients with high risk of CAN for colonoscopy priority.

Tuberculosis and mental health in the Asia-Pacific.

OBJECTIVE: This opinion piece encourages mental health researchers and clinicians to engage with mental health issues among tuberculosis patients in the Asia-Pacific region in a culturally appropriate and ethical manner. The diversity of cultural contexts and the high burden of tuberculosis throughout the Asia-Pacific presents significant challenges. Research into tuberculosis and mental illness in this region is an opportunity to develop more nuanced models of mental illness and treatment, while simultaneously contributing meaningfully to regional tuberculosis care and prevention. CONCLUSIONS: We overview key issues in tuberculosis and mental illness co-morbidity, highlight ethical concerns and advocate for a regional approach to tuberculosis and mental health that is consistent with the transnational challenges presented by this airborne infectious disease. Integrating tuberculosis and mental health services will go a long way to addressing the needs of vulnerable populations and stopping the transmission of one of the world's biggest infectious killers.

Population-wide active case finding as a strategy to end TB.

Tuberculosis (TB) is the leading infectious cause of morbidity and mortality globally. Despite available tools for preventing, finding, and treating TB, many people with TB remain undiagnosed. In high-incidence settings, TB transmission is ubiquitous within the community, affecting both high-risk groups and the general population. In fact, most people who develop TB come from the general population. To disrupt the chain of transmission that sustains the TB epidemic, we need to find and treat everyone with infectious TB as early as possible, including those with minimal symptoms or subclinical TB who are unlikely to present for care. Important elements of an effective active case-finding strategy include effective social mobilisation and community engagement, using sensitive screening tools that can be used at scale, and embracing population-wide screening in high-incidence ('hot spot') areas. We require a better description of feasible delivery models, 'real-life' impact and cost effectiveness to enable wider implementation.

Health system barriers to the implementation of the national action plan to combat antimicrobial resistance in Vietnam: a scoping review.

BACKGROUND: Vietnam is among 11 countries in the Western Pacific region that has developed a National Action Plan for Antimicrobial Resistance (NAPCA). METHODS: This scoping review characterises health system barriers to the implementation of the Vietnam NAPCA, with reference to the WHO Health Systems Framework. RESULTS: Over 7 years, between 2013 and 2020, the Ministry of Health (MOH) of Vietnam has been implementing activities to achieve the six NAPCA objectives. They include revision of regulations needed for antimicrobial resistance (AMR) prevention programs; formation and operation of national management bodies; improvement of antimicrobial stewardship (AMS) in hospitals; maintenance of surveillance systems for AMR; provision of trainings on AMR and antibiotics use to doctors and pharmacists; and organization of nation-wide educational campaigns. Limited cooperation between MOH management bodies, shortages of human resource at all health system levels, a low degree of agreement between national and hospital guidelines on antibiotic use, low capability in the domestic supply of standardised drugs, and unequal training opportunities for lower-level health professionals present ongoing challenges. Actions suggested for the next period of the NAPCA include a final review of what has been achieved by the plan so far and evaluating the effectiveness of the different components of the plan. Different options on how to improve coordination across sectors in the development of a new NAPCA should be put forward. CONCLUSIONS: The 6-year implementation of the Vietnam NAPCA has yielded valuable lessons for AMS in Vietnam, guiding the development of future national plans, with a central focus on scaling up AMS in hospitals and promoting community AMS programs to combat AMR.

High-dose, short-duration versus standard rifampicin for tuberculosis preventive treatment: a partially blinded, three-arm, non-inferiority, randomised, controlled trial.

BACKGROUND: Tuberculosis preventive treatment (TPT) is a key component of tuberculosis elimination. To improve completion and reduce the burden for people and health systems, short, safe, and effective TPT regimens are needed. We aimed to compare safety and treatment completion of various doses and durations of rifampicin in people who were recommended to receive TPT. METHODS: This partially blinded, parallel-arm, non-inferiority, randomised, controlled, phase 2b trial was done at seven university-affiliated clinics in Canada, Indonesia, and Viet Nam. Participants aged 10 years or older were included if they had an indication for TPT according to WHO guidelines for Indonesia and Viet Nam, or Canadian guidelines for Canadian sites, and a positive tuberculin skin test or interferon-γ release assay. Participants were randomly assigned (1:1:1) to receive oral rifampicin at 10 mg/kg once daily for 4 months (standard-dose group), 20 mg/kg daily for 2 months (20 mg/kg group), or 30 mg/kg daily for 2 months (30 mg/kg group). The randomisation sequence was computer generated with blocks of variable size (three, six, and nine) and stratified by country for Indonesia and Viet Nam, and by city within Canada. Participants and investigators were masked to dose in high-dose groups, but unmasked to duration in all groups. The two co-primary outcomes were safety (in the safety population, in which participants received at least one dose of the study drug) and treatment completion (in the modified intention-to-treat [mITT] population, excluding those ineligible after randomisation). Protocol-defined adverse events were defined as grade 3 or worse, or rash or allergy of any grade, judged by an independent and masked panel as possibly or probably related to the study. A margin of 4% was used to assess non-inferiority. This study is registered with ClinicalTrials.gov, NCT03988933 (active). FINDINGS: Between Sept 1, 2019, and Sept 30, 2022, 1692 people were assessed for eligibility, 1376 were randomly assigned, and eight were excluded after randomisation. 1368 participants were included in the mITT population (454 in the standard group, 461 in the 20 mg/kg group, and 453 in the 30 mg/kg group). 589 (43%) participants were male and 779 (57%) were female. 372 (82%) in the standard-dose group, 329 (71%) in the 20 mg/kg group, and 293 (65%) in the 30 mg/kg group completed treatment. No participants in the standard-dose group, one (<1%) of 441 participants in the 20 mg/kg group, and four (1%) of 423 in the 30 mg/kg group developed grade 3 hepatotoxicity. Risk of protocol-defined adverse events was higher in the 30 mg/kg group than in the standard-dose group (adjusted risk difference 4·6% [95% CI 1·8 to 7·4]) or the 20 mg/kg group (5·1% [2·3 to 7·8]). There was no difference in the risk of adverse events between the 20 mg/kg and standard-dose groups (-0·5% [95% CI -2·4 to 1·5]; non-inferiority met). Completion was lower in the 20 mg/kg group (-7·8% [95% CI -13·6 to -2·0]) and the 30 mg/kg group (-15·4% [-21·4 to -9·4]) than in the standard-dose group. INTERPRETATION: In this trial, 2 months of 30 mg/kg daily rifampicin had significantly worse safety and completion than 4 months of 10 mg/kg daily and 2 months of 20 mg/kg daily (the latter, a fully blinded comparison); we do not consider 30 mg/kg to be a good option for TPT. Rifampicin at 20 mg/kg daily for 2 months was as safe as standard treatment, but with lower completion. This difference remains unexplained. FUNDING: Canadian Institutes of Health Research.

Sustainability and impact of an intervention to improve initiation of tuberculosis preventive treatment: results from a follow-up study of the ACT4 randomized trial.

Background: In a cluster randomized trial (clinicaltrials.gov: NCT02810678) a flexible but comprehensive health system intervention significantly increased the number of household contacts (HHC) identified and started on tuberculosis preventive treatment (TPT). A follow-up study was conducted one year later to test the hypotheses that these effects were sustained, and were reproducible with a simplified intervention. Methods: We conducted a follow-up study from May 1, 2018 until April 30, 2019, as part of a multinational cluster randomized trial. Eight sites in 4 countries that had received the intervention in the original trial received no further intervention; eight other sites in the same countries that had not received the intervention (control sites in the original trial) now received a simplified version of the intervention. This consisted of repeated local evaluation of the Cascade of care for TB infection, and stakeholder decision making. The number of HHC identified and starting TPT were repeatedly measured at all 16 sites and expressed as rates per 100 newly diagnosed index TB patients. The sustained effect of the original intervention was estimated by comparing these rates after the intervention in the original trial with the last 6 months of the follow-up study. The reproducibility was estimated by comparing the pre-post intervention changes in rates at sites receiving the original intervention with the pre-post changes in rates at sites receiving the later, simplified intervention. Findings: With regard to the sustained impact of the original intervention, compared to the original post-intervention period, the number of HHC identified and treated per 100 newly diagnosed TB patients was 10 more (95% confidence interval: 84 fewer to 105 more), and 1 fewer (95% CI: 22 fewer to 20 more) respectively up to 14 months after the end of the original intervention. With regard to the reproducibility of the simplified intervention, at sites that had initially served as control sites, the number of HHC identified and treated per 100 TB patients increased by 33 (95% CI: -32, 97), and 16 (-69, 100) from 3 months before, to up to 6 months after receiving a streamlined intervention, although differences were larger, and significant if the post-intervention results were compared to all pre-intervention periods. Interpretation: Up to one year after it ended, a health system intervention resulted in sustained increases in the number of HHC identified and starting TPT. A simplified version of the intervention was associated with non-significant increases in the identification and treatment of HHC. Inferences are limited by potential bias due to other temporal effects, and the small number of study sites. Funding: Funded by the Canadian Institutes of Health Research (Grant number 143350).

Finding and treating both tuberculosis disease and latent infection during population-wide active case finding for tuberculosis elimination.

In recognition of the high rates of undetected tuberculosis in the community, the World Health Organization (WHO) encourages targeted active case finding (ACF) among "high-risk" populations. While this strategy has led to increased case detection in these populations, the epidemic impact of these interventions has not been demonstrated. Historical data suggest that population-wide (untargeted) ACF can interrupt transmission in high-incidence settings, but implementation remains lacking, despite recent advances in screening tools. The reservoir of latent infection-affecting up to a quarter of the global population -complicates elimination efforts by acting as a pool from which future tuberculosis cases may emerge, even after all active cases have been treated. A holistic case finding strategy that addresses both active disease and latent infection is likely to be the optimal approach for rapidly achieving sustainable progress toward TB elimination in a durable way, but safety and cost effectiveness have not been demonstrated. Sensitive, symptom-agnostic community screening, combined with effective tuberculosis treatment and prevention, should eliminate all infectious cases in the community, whilst identifying and treating people with latent infection will also eliminate tomorrow's tuberculosis cases. If real strides toward global tuberculosis elimination are to be made, bold strategies are required using the best available tools and a long horizon for cost-benefit assessment.

High dose rifampin for 2 months vs standard dose rifampin for 4 months, to treat TB infection: Protocol of a 3-arm randomized trial (2R2).

INTRODUCTION: Tuberculosis preventive treatment (TPT) is an essential component for TB elimination. In order to be successfully implemented on a large scale, TPT needs to be safe, affordable and widely available in all settings. Short TPT regimens, that are less burdensome than longer regimens, to patients and health systems, are needed. Doses of rifampin higher than the standard 10mg/kg/day were tolerated in studies to reduce duration of treatment for tuberculosis disease (TBD). The objective of this trial is to test the safety of high dose rifampin monotherapy to shorten the duration of the currently recommended TPT of 4 months rifampin. METHODS AND ANALYSIS: This is a phase 2b, randomised, controlled, parallel group, superiority, partially-blind trial. Primary outcomes are completion of treatment (as a proxy measure of tolerability) and safety. The two experimental arms comprise 60 days of (i) 20mg/kg/day or (ii) 30mg/kg/day rifampin; the control arm comprises 120 days of 10mg/kg/day rifampin as TPT. Participants are adults and children 10 years or older, eligible for TPT. Completion is the primary outcome, measured by pill count and is defined as taking minimum of 80% of treatment in 120% of allowed time; it will be tested for superiority by logistic regression. Safety outcome comprises proportion of grade 3-5 adverse events and grade 1-2 rash, adjudicated related to study drug, and resulting in permanent drug discontinuation; compared for non-inferiority between each of the two high dose arms and the standard arm, using Poisson regression. A sample size of 1,359 participants will give 80% power to detect a 10% difference in completion rates and a 1% difference in the safety outcome. The study is conducted in Canada, Indonesia and Vietnam. Enrolment is ongoing at all sites. ETHICS AND DISSEMINATION: Approvals from a local research ethics board (REB) have been obtained at all participating sites and by the trial coordinating centre. Approval has been given by drug regulatory agencies in Canada and Indonesia and by Ministry of Health in Vietnam; participants give written informed consent before participation. All data collected are non-nominal. Primary results will be submitted for publication in a peer-reviewed journal when all participants have completed treatment; results of secondary outcomes will be submitted for publication at the end of study; all sites will receive the final data of participants from their sites. TRIAL REGISTRATION: Trial registered in ClinicalTrials.gov (Identifier: NCT03988933). Coordinating center is the study team working at McGill University Health Center-Research Institute (MUHC-RI); sponsor is the MUHC-RI; funding has been granted by Canadian Institute of Health Research (FDN-143350).

The inclusion of diagnostics in national health insurance schemes in Cambodia, India, Indonesia, Nepal, Pakistan, Philippines and Viet Nam.

The Lancet Commission on Diagnostics highlighted a huge gap in access to diagnostic testing even for basic tests, particularly at the primary care level, and emphasised the need for countries to include diagnostics as part of their universal health coverage benefits packages. Despite the poor state of diagnostic-related services in low-income and middle-income countries (LMICs), little is known about the extent to which diagnostics are included in the health benefit packages. We conducted an analysis of seven Asian LMICs-Cambodia, India, Indonesia, Nepal, Pakistan, Philippines, Viet Nam-to understand this issue. We conducted a targeted review of relevant literature and applied a health financing framework to analyse the benefit packages available in each government-sponsored scheme. We found considerable heterogeneity in country approaches to diagnostics. Of the seven countries, only India has developed a national essential diagnostics list. No country presented a clear policy rationale on the inclusion of diagnostics in their scheme and the level of detail on the specific diagnostics which are covered under the schemes was also generally lacking. Government-sponsored insurance expansion in the eligible populations has reduced the out-of-pocket health payment burden in many of the countries but overall, there is a lack of access, availability and affordability for diagnostic-related services.