Priority Activities in Child and Adolescent Tuberculosis to Close the Policy-Practice Gap in Low- and Middle-Income Countries.

Over the past 15 years, and despite many difficulties, significant progress has been made to advance child and adolescent tuberculosis (TB) care. Despite increasing availability of safe and effective treatment and prevention options, TB remains a global health priority as a major cause of child and adolescent morbidity and mortality-over one and a half million children and adolescents develop TB each year. A history of the global public health perspective on child and adolescent TB is followed by 12 narratives detailing challenges and progress in 19 TB endemic low and middle-income countries. Overarching challenges include: under-detection and under-reporting of child and adolescent TB; poor implementation and reporting of contact investigation and TB preventive treatment services; the need for health systems strengthening to deliver effective, decentralized services; and lack of integration between TB programs and child health services. The COVID-19 pandemic has had a significant negative impact on case detection and treatment outcomes. Child and adolescent TB working groups can address country-specific challenges to close the policy-practice gaps by developing and supporting decentral ized models of care, strengthening clinical and laboratory diagnosis, including of multidrug-resistant TB, providing recommended options for treatment of disease and infection, and forging strong collaborations across relevant health sectors.

Population benefits of addressing programmatic and social determinants of gender disparities in tuberculosis in Viet Nam: A modelling study.

High prevalence of infectious tuberculosis among men suggests potential population-wide benefits from addressing programmatic and social determinants of gender disparities. Utilising a sex-stratified compartmental transmission model calibrated to tuberculosis burden estimates for Viet Nam, we modelled interventions to increase active case finding, to reduce tobacco smoking, and to reduce alcohol consumption by 2025 in line with national and global targets. For each intervention, we examined scenarios differentially targeting men and women and evaluated impact on tuberculosis morbidity and mortality in men, women, and children in 2035. Active case finding interventions targeting men projected greater reductions in tuberculosis incidence in men, women, and children (16.2%, uncertainty interval, UI, 11.4-23.0%, 11.8%, UI 8.0-18.6%, and 21.5%, UI 16.9-28.5%, respectively) than those targeting women (5.2%, UI 3.8-7.1%, 5.4%, UI 3.9-7.3%, and 8.6%, UI 6.9-10.7%, respectively). Projected reductions in tuberculosis incidence for interventions to reduce male tobacco smoking and alcohol consumption were greatest for men (17.4%, UI 11.8-24.7%, and 11.0%, UI 5.4-19.4%, respectively), but still substantial for women (6.9%, UI 3.8-12.5%, and 4.4%, UI 1.9-10.6%, respectively) and children (12.7%, UI 8.4-19.0%, and 8.0%, UI 3.9-15.0%, respectively). Comparable interventions targeting women projected limited impact, with declines of 0.3% (UI 0.2%-0.3%) and 0.1% (UI 0.0%-0.1%), respectively. Addressing programmatic and social determinants of men's tuberculosis burden has population-wide benefits. Future interventions to increase active case finding, to reduce tobacco smoking, and to reduce harmful alcohol consumption, whilst not ignoring women, should focus on men to most effectively reduce tuberculosis morbidity and mortality in men, women, and children.

Active surveillance for adverse events in patients on longer treatment regimens for multidrug-resistant tuberculosis in Viet Nam.

OBJECTIVE: Management of multidrug-resistant tuberculosis (MDR-TB) is a significant challenge to the global healthcare system due to the complexity and long duration of the MDR-TB treatment. This study analyzed the safety of patients on longer injectable-based MDR-TB treatment regimens using active pharmacovigilance data. METHOD: We conducted an observational, prospective study based on active pharmacovigilance within the national TB program. A total of 659 MDR-TB patients were enrolled and followed up at 9 TB- hospitals in 9 provinces of all 3 regions in Vietnam between 2014 and 2016. Patients received a treatment regimen (standardized or individualized) based on their drug susceptibility test result and their treatment history. Baseline and follow-up information was collected at the start and during treatment. Adverse events (AE) were defined and classified as serious adverse events (SAEs) or otherwise. Multivariate Cox regression following the Iterative Bayesian Model Averaging algorithm was performed to identify factors associated with AE occurrence. RESULTS: Out of 659 patients assessed, 71.3% experienced at least one AE, and 17.5% suffered at least one SAE. The most common AEs were gastrointestinal disorders (38.5%), arthralgia (34.7%), and psychiatric disorders (30.0%). The proportion of patients with nephrotoxicity and hearing loss or vestibular disorders were 7.4% and 15.2%, respectively. 13.1% of patients required modifications or interruption of one or more drugs. In 77.7% of patients, treatment was completed successfully, while 9.3% lost to follow-up, in 3.0% treatment failed, and 7.4% died. Some significant risk factors for nephrotoxicity included diabetes mellitus (HR = 8.46 [1.91-37.42]), renal dysfunction (HR = 8.46 [1.91-37.42]), alcoholism (HR = 13.28 [5.04-34.99]), and a higher average daily dose of injectable drugs (HR = 1.28 [1.14-1.43]). CONCLUSION: While a majority of patients on the longer injectable-based regimens experienced non-serious AEs during MDR-TB treatment, one in six patients experienced at least an SAE. Active TB drug-safety monitoring is useful to understand the safety of MDR-TB treatment and explore the risk factors for toxicity. All-oral, shorter MDR-TB regimens might be able to reduce the inconvenience, discomfort, and toxicity of such regimens and increase adherence and likelihood of successful completion.

GeneXpert on patients with human immunodeficiency virus and smear-negative pulmonary tuberculosis.

OBJECTIVES: Vietnam is a high-prevalence country for tuberculosis (TB). Xpert MTB/RIF is a novel PCR-based diagnostic test that is substantially more sensitive for detecting M. tuberculosis than traditional smear-based techniques. However, locally-derived evidence of Xpert MTB/RIF in HIV-infected people is limited. This study evaluates the performance of the Xpert MTB/RIF in HIV-infected patients with smear-negative pulmonary TB (SNTB). METHODS: This was a cross-sectional study in 3 hospitals. The performance of Xpert MTB/RIF was compared with the reference standard of liquid culture and phenotypic drug-susceptibility testing for rifampicin (RIF) resistance. RESULTS: Out of 123 patients, the median age was 37.0 (IQR: 32.0-41.0) and 81.3% were male. The area under the receiver operating characteristic curve, sensitivity (Se) and specificity (Sp) of Xpert MTB/RIF for pulmonary TB diagnosis were 0.72 (95% confidence interval [CI]: 0.63-0.81), 66.7% (95%CI: 54.8-77.1) and 77.1% (95%CI: 62.7-88.0), respectively, while Se and Sp of Xpert MTB/RIF in detecting RIF resistance were 50.0 (11.8-88.2) and 86.4% (95%CI: 72.7-94.8). CONCLUSION: The performance of Xpert MTB/RIF in HIV-infected patients with SNTB for the diagnosis of TB and RIF-resistance was low. Further studies are required to evaluate the results of Xpert MTB/RIF assay in HIV-infected patients with SNTB and the role of Xpert repetition on the same specimens.

Risk Factors for Tuberculosis (TB) Among Household Contacts of Patients With Smear-Positive TB in 8 Provinces of Vietnam: A Nested Case-Control Study.

BACKGROUND: Tuberculosis (TB) continues to account for significant morbidity and mortality annually. Household contacts (HHCs) of persons with TB are a key population for targeting prevention and control interventions. We aimed to identify risk factors associated with developing TB among HHCs. METHODS: We conducted a nested case-control study among HHCs in 8 provinces in Vietnam enrolled in a randomized controlled trial of active case finding for TB. Cases were any HHCs diagnosed and registered with TB within the Vietnam National TB Program during 2 years of follow-up. Controls were selected by simple random sampling from the remaining HHCs. Risk factor data were collected at enrollment and during follow-up. A logistic regression model was developed to determine predictors of TB among HHCs. RESULTS: We selected 1254 HHCs for the analysis: 214 cases and 1040 controls. Underlying characteristics varied between both groups; cases were older, more likely to be male, with a higher proportion of reported previous TB and diabetes. Risk factors associated with a TB diagnosis included being male (adjusted odds ratio [aOR], 1.4; 95% confidence interval [CI], 1.03-2.0), residing in an urban setting (aOR, 1.8; 1.3-2.5), prior TB (aOR, 4.6; 2.5-8.7), history of diabetes (aOR, 3.1; 1.7-5.8), current smoking (aOR, 3.1; 2.2-4.4), and prolonged history of coughing in the index case at enrollment (OR , 1.6; 1.1-2.3). CONCLUSIONS: Household contacts remain an important key population for TB prevention and control. TB programs should ensure effective contact investigations are implemented for household contacts, particularly those with additional risk factors for developing TB.

The Financial Burden of Tuberculosis for Patients in the Western-Pacific Region.

The End Tuberculosis (TB) Strategy has the ambitious goal of ending the global TB epidemic by the year 2030, which is aligned to the Sustainable Development Goals. One of three high level indicators of the Strategy is the "catastrophic costs" indicator, which aims to determine the proportion of TB-affected households that incur TB-care related costs equivalent to 20% or more of their annual household income. The target is that zero percentage of TB-affected households will incur catastrophic costs related to TB care by the year 2020. In the Western Pacific Region of the World Health Organization, it is a priority to determine the financial burden of TB and then act to mitigate it. To date, eight countries in the Region have conducted nationally representative TB patient cost surveys to determine the costs of TB care. The results from four countries that have completed these surveys (i.e., Fiji, Mongolia, the Philippines, and Vietnam) indicate that between 35% and 70% of TB patients face catastrophic costs related to their TB care. With these results in mind, significant additional efforts are needed to ensure financial risk protection for TB patients, expand Universal Health Coverage, and improve access to social protection interventions. A multi-sectoral approach is necessary to achieve this ambitious goal by the year 2020.

Progress towards universal HIV testing among TB patients in Viet Nam: a retrospective cohort evaluation of TB/HIV surveillance, 2011-2017.

BACKGROUND: Tuberculosis (TB) and HIV remain a major causes of morbidity and mortality globally. We conducted an analysis of TB/HIV surveillance data to describe the trends in HIV testing coverage and HIV positivity rate among TB patients in Viet Nam, 2011-2017. MAIN TEXT: This was a descriptive study based on review and analysis of surveillance data from the National Tuberculosis Control Programme from 2011 to 2017. During this period, 721 342 TB cases were diagnosed. Of these, 520 490 (72.2%) had a previously documented HIV status or were tested for HIV during TB care and treatment. The proportion of TB patients whose HIV status was reported increased, from 58.5% in 2011 to 82.9% in 2017 (P value for trend = 0.014). The proportion of TB patients infected with HIV decreased, from 8.0% in 2011 to 3.7% in 2017 (P value for trend = 0.018). CONCLUSIONS: The proportion of TB patients with a reported HIV status was increased from 2011 to 2017, however HIV testing coverage remained below the National Tuberculosis Control Programme targets (≥ 90%). National Tuberculosis Control Programme needs to focus on ensuring every registered TB patients has a documented HIV status, ensuring full coverage of HIV testing as part of routine TB care.

Household contact investigation for the detection of tuberculosis in Vietnam: economic evaluation of a cluster-randomised trial.

BACKGROUND: Active case finding is recommended as an important strategy to control tuberculosis, particularly in low-income and middle-income countries with a high prevalence of the disease. However, the costs and cost-effectiveness of active case finding are unclear due to the absence of evidence from randomised trials. We assessed the costs and cost-effectiveness of an active case finding strategy in Vietnam, where there is a high prevalence of tuberculosis. METHODS: We conducted an economic evaluation alongside the Active Case Finding in Tuberculosis (ACT2) trial-a pragmatic cluster-randomised controlled trial in 70 districts across eight provinces of Vietnam. Patients aged 15 years and older with smear-positive pulmonary tuberculosis were recruited to the trial if they lived with one or more other household members. Household contacts were verbally invited to the clinic by the index patient with tuberculosis. ACT2 compared a combination of active and passive case finding with usual care (passive case finding) of household contacts of patients with tuberculosis from a health system perspective. Clustering occurred at the district and household level. Districts were the unit of randomisation, and we used minimisation to ensure balance of intervention and control districts within each province. In the intervention group, participants were invited to attend screening at baseline, 6 months, 12 months, and 24 months. We determined health-care costs with a standardised national costing survey and reported results in 2017 $US. The primary outcome of our study was disability-adjusted life years (DALYs) averted over a 24-month period. ACT2 was registered prospectively with the Australian and New Zealand Clinical Trials Registry, number ACTRN126.100.00600044. FINDINGS: Between Aug 11, 2010, and Aug 11, 2015, 10 964 index patients and 25 707 household contacts completed the ACT2 study. There were 10 069 household contacts in the intervention group and 15 638 household contacts in the control group. The incremental cost-effectiveness ratio per DALY averted was $544 (330-1375). INTERPRETATION: Active case finding was shown to be highly cost-effective in a setting with a high prevalence of tuberculosis. Investment in the wide-scale implementation of this programme in Vietnam should be strongly supported. FUNDING: Australian National Health and Medical Research Council.

Active case-finding for tuberculosis by mobile teams in Myanmar: yield and treatment outcomes.

BACKGROUND: Since 2005, the Myanmar National Tuberculosis Programme (NTP) has been implementing active case finding (ACF) activities involving mobile teams in hard-to-reach areas. This study revealed the contribution of mobile team activities to total tuberculosis (TB) case detection, characteristics of TB patients detected by mobile teams and their treatment outcomes. METHODS: This was a descriptive study using routine programme data between October 2014 and December 2014. Mobile team activities were a one-stop service and included portable digital chest radiography (CXR) and microscopy of two sputum samples. The algorithm of the case detection included screening patients by symptoms, then by CXR followed by sputum microscopy for confirmation. Diagnosed patients were started on treatment and followed until a final outcome was ascertained. RESULTS: A total of 9 349 people with symptoms suggestive of TB were screened by CXR, with an uptake of 96.6%. Of those who were meant to undergo sputum smear microscopy, 51.4% had sputum examinations. Finally, 504 TB patients were identified by the mobile teams and the overall contribution to total TB case detection in the respective townships was 25.3%. Among total cases examined by microscopy, 6.4% were sputum smear positive TB. Treatment success rate was high as 91.8% in study townships compared to national rate 85% (2014 cohort). CONCLUSIONS: This study confirmed the feasibility and acceptability of ACF by mobile teams in hard-to-reach contexts, especially when equipped with portable, digital CXR machines that provided immediate results. However, the follow-up process of sputum examination created a significant barrier to confirmation of the diagnosis. In order to optimize the ACF through mobile team activity, future ACF activities were needed to be strengthened one stop service including molecular diagnostics or provision of sputum cups to all presumptive TB cases prior to CXR and testing if CXR suggestive of TB.

The contribution of a non-governmental organisation's Community Based Tuberculosis Care Programme to case finding in Myanmar: trend over time.

BACKGROUND: It is estimated that the standard, passive case finding (PCF) strategy for detecting cases of tuberculosis (TB) in Myanmar has not been successful: 26% of cases are missing. Therefore, alternative strategies, such as active case finding (ACF) by community volunteers, have been initiated since 2011. This study aimed to assess the contribution of a Community Based TB Care Programme (CBTC) by local non-government organizations (NGOs) to TB case finding in Myanmar over 4 years. METHODS: This was a descriptive study using routine, monitoring data. Original data from the NGOs were sent to a central registry within the National TB Programme and data for this study were extracted from that database. Data from all 84 project townships in five regions and three states in Myanmar were used. The project was launched in 2011. RESULTS: Over time, the number of presumptive TB cases that were referred decreased, except in the Yangon Region, although in some areas, the numbers fluctuated. At the same time, there was a trend for the proportion of cases treated, compared to those referred, that decreased over time (P = 0.051). Overall, among 84 townships, the contribution of CBTC to total case detection deceased from 6% to 4% over time (P < 0.001). CONCLUSIONS: Contrary to expectations and evidence from previous studies in other countries, a concerning reduction in TB case finding by local NGO volunteer networks in several areas in Myanmar was recorded over 4 years. This suggests that measures to support the volunteer network and improve its performance are needed. They may include discussion with local NGOs human resources personnel, incentives for the volunteers, closer supervision of volunteers and improved monitoring and evaluation tools.

Adverse events in the treatment of MDR-TB patients within and outside the NTP in Pham Ngoc Thach hospital, Ho Chi Minh City, Vietnam.

BACKGROUND: Treatment outcomes of a high proportion of inpatients with multi-drug resistant tuberculosis (MDR-TB) were not reported to the Vietnamese National Tuberculosis Program because they received treatment outside of the green light committee (GLC) program. The study aimed (1) to describe the strengths and weaknesses of treatment of GLC and non-GLC MDR-TB patients as well as the factors influencing treatment completion and (2) to determine the incidence of adverse drug reactions. RESULTS: This cross-sectional study comprised two elements: (1) in-depth interviews with clinical doctors, hospital pharmacists; and focus group discussions with MDR-TB patients; and (2) a review of the charts of all GLC and non-GLC MDR-TB patients in 2010. A total of 282 MDR-TB patients were recruited, including 79(28%) MDR-TB patients treated through the GLC program and 203(72%) MDR-TB patients treated outside of the GLC program. The main strengths of GLC treatment were the supply of quality assured second line TB drugs, routine monitoring and clinical evaluation, free diagnostic tests and close clinical monitoring. The greatest barriers to patients treated outside of the GLC program was difficulty paying for second line TB drugs and other treatment costs. There was no significant difference between the incidence of adverse events among GLC (46.8%) and non-GLC treated patients (52.2%; p = 0.417). Among 143 patients who reported 226 adverse reaction events, arthralgia/joint pain (35.8%), gastrointestinal (14.2%), ototoxicity (8.4%), cutaneous (6.6%), and giddiness (5.8%) were the most common. CONCLUSIONS: The non-GLC MDR-TB patients face substantial barriers to treatment, and require greater support if they are to complete treatment and improve disease outcomes. Staff training about the management of adverse drug reactions is needed.

Tuberculosis case notification data in Viet Nam, 2007 to 2012.

Tuberculosis (TB) remains a major cause of morbidity and mortality, and Viet Nam ranks 12 among the 22 high-TB burden countries. This study analyses surveillance data of the National Tuberculosis Control Programme in Viet Nam for the six-year period 2007 to 2012. During the study period, 598,877 TB cases (all forms) were notified, and 313,225 (52.3%) were new smear-positive cases. The case notification rate of new smear-positive cases was decreased, from 65 per 100,000 population in 2007 to 57 per 100,000 population in 2012; this decrease was observed for males and females in all age groups except males aged 0-14 and females aged 15-24 years. The male-to-female ratio of new smear-positive TB cases increased from 2.85 in 2007 to 3.02 in 2012. The average annual cure rate of new smear-positive cases was 90.3%. The high male-to-female ratio for new smear-positive TB cases in this notification data was lower than that from the 2007 TB prevalence survey in Viet Nam, suggesting a lower case detection for males. The decrease in new smear-positive case notification rates may reflect a decline in TB incidence in Viet Nam as several programmatic improvements have been made, although further research is required to increase case detection among young males and children.

National survey of tuberculosis prevalence in Viet Nam.

OBJECTIVE: To estimate the prevalence of tuberculosis in Viet Nam with data from a population-based survey, compare it with the prevalence estimated by the World Health Organization, and identify major demographic determinants of tuberculosis prevalence. METHODS: A cross-sectional survey with multistage cluster sampling, stratified by urban, rural and remote areas, was done in 2006-2007 in 70 communes. All inhabitants aged > or = 15 years were invited for cough and chest X-ray examination. Participants with findings suggestive of tuberculosis provided sputum specimens for smear examination and culture. Point prevalence estimates, 95% confidence intervals and design effects were calculated. Confidence intervals and P-values were adjusted for the cluster design. FINDINGS: Of 114,389 adult inhabitants, 94 179 (82.3%) were screened. Of 87,314 (92.7%) screened by both questionnaire and chest X-ray, 3522 (4.0%) had productive cough, 518 (0.6%) had a recent history of tuberculosis and 2972 (3.4%) had chest X-ray abnormalities suggestive of tuberculosis. Sputum tests were done for 7648 participants. Sputum test, bacterial culture or both confirmed 269 tuberculosis cases, 174 of which were smear-positive. The prevalence rate of smear-positive tuberculosis was 145 per 100,000 (95% confidence interval: 110-180) assuming no tuberculosis in persons aged < 15 years. Prevalence was 5.1 times as high in men as in women, increased with age, was higher in rural than in urban or remote areas and showed a north-to-south gradient. CONCLUSION: In Viet Nam, the tuberculosis prevalence rate based on positive sputum smear tests was 1.6 times as high as previously estimated. Age and sex patterns were consistent with notification data. Tuberculosis control should remain a high priority in Viet Nam.