Prevalence of extra-pulmonary tuberculosis in Africa: A systematic review and meta-analysis.

OBJECTIVE: The burden of extra-pulmonary tuberculosis (EPTB) is not well quantified in TB endemic countries such as those in sub-Saharan Africa. This study aimed to quantify that burden via a systematic review of the prevalence of EPTB in African countries. METHODS: Studies were retrieved by searching five databases; 105 studies published between 1990 and 2023 were included. The studies described the prevalence of EPTB among the general population (4 studies), TB patients (68) and patients with other conditions, including HIV (15), meningitis (3), renal failure (3) and other comorbidities, some of which are cancer (12). Due to the low number of studies reporting EPTB in patients with conditions other than TB, the meta-analysis was performed on studies reporting on EPTB among TB patients (68 studies). Meta-analysis was performed on the 68 studies (271,073 participants) using a random-effects model to estimate the pooled prevalence of EPTB. Meta-regression was used to explore possible explanations for heterogeneity according to regions and time periods. RESULTS: The pooled prevalence of EPTB among TB patients was 26% (95% CI 23-29%). There was substantial heterogeneity of prevalence for the five African regions. The Eastern region had the highest prevalence of 32% (95% CI 28-37%) and the lowest in Western Africa, 16% (95% CI 10-24%). There was no significant difference in the prevalence of EPTB between the 3 eleven-year time periods. CONCLUSIONS: Our systematic review and meta-analysis give insight into the burden of EPTB in Africa. This review could inform clinical and programmatic practices-a higher suspicion index for clinicians and more effort for better services. This could contribute to efforts aiming to end TB, which have historically been focused on PTB.Coordinated efforts that target both EPTB and PTB are needed.

Tuberculosis in older adults: challenges and best practices in the Western Pacific Region.

The Western Pacific has one of the fastest-growing older adult populations globally, and tuberculosis (TB) remains one of the foremost infectious causes of disease and death in the region. Older adults are at higher risk of TB due to immunosenescence, comorbidities, and increased institutionalisation. Atypical symptoms and reduced access to health services may delay care-seeking and TB diagnosis, while co-morbidity and increased risk of adverse drug reactions complicate TB treatment. Post-TB sequelae and socioeconomic challenges may decrease the quality of life after TB treatment completion. Despite their high disease burden and special challenges, there is a lack of regionally coordinated policies and guidelines to manage TB among older adults. Routine TB screening at aged-care facilities, age-friendly infrastructure and services, awareness of atypical TB features, integration of TB and non-communicable diseases services, and person-centred approaches to treatment support could improve TB management among older adults. Addressing these challenges and adopting the best practices identified should inform policy formulation and implementation. Funding: This project was funded by 1) the World Health Organization Regional Office for the Western Pacific, with financial contributions from the Government of the Republic of Korea through the Korean Disease Control and Prevention Agency and the Government of Japan through the Ministry of Health, Labour and Welfare, and 2) NUS Start-up Grant. The funders had no role in the paper design, collection, analysis, and interpretation of data and in writing of the paper.

A model-based approach for a practical dosing strategy for the short, intensive treatment regimen for paediatric tuberculous meningitis.

Following infection with Mycobacterium tuberculosis, young children are at high risk of developing severe forms of tuberculosis (TB) disease, including TB meningitis (TBM), which is associated with significant morbidity and mortality. In 2022, the World Health Organization (WHO) conditionally recommended that a 6-month treatment regimen composed of higher doses of isoniazid (H) and rifampicin (R), with pyrazinamide (Z) and ethionamide (Eto) (6HRZEto), be used as an alternative to the standard 12-month regimen (2HRZ-Ethambutol/10HR) in children and adolescents with bacteriologically confirmed or clinically diagnosed TBM. This regimen has been used in South Africa since 1985, in a complex dosing scheme across weight bands using fixed-dose combinations (FDC) available locally at the time. This paper describes the methodology used to develop a new dosing strategy to facilitate implementation of the short TBM regimen based on newer globally available drug formulations. Several dosing options were simulated in a virtual representative population of children using population PK modelling. The exposure target was in line with the TBM regimen implemented in South Africa. The results were presented to a WHO convened expert meeting. Given the difficulty to achieve simple dosing using the globally available RH 75/50 mg FDC, the panel expressed the preference to target a slightly higher rifampicin exposure while keeping isoniazid exposures in line with those used in South Africa. This work informed the WHO operational handbook on the management of TB in children and adolescents, in which dosing strategies for children with TBM using the short TBM treatment regimen are provided.

Development of treatment-decision algorithms for children evaluated for pulmonary tuberculosis: an individual participant data meta-analysis.

BACKGROUND: Many children with pulmonary tuberculosis remain undiagnosed and untreated with related high morbidity and mortality. Recent advances in childhood tuberculosis algorithm development have incorporated prediction modelling, but studies so far have been small and localised, with limited generalisability. We aimed to evaluate the performance of currently used diagnostic algorithms and to use prediction modelling to develop evidence-based algorithms to assist in tuberculosis treatment decision making for children presenting to primary health-care centres. METHODS: For this meta-analysis, we identified individual participant data from a WHO public call for data on the management of tuberculosis in children and adolescents and referral from childhood tuberculosis experts. We included studies that prospectively recruited consecutive participants younger than 10 years attending health-care centres in countries with a high tuberculosis incidence for clinical evaluation of pulmonary tuberculosis. We collated individual participant data including clinical, bacteriological, and radiological information and a standardised reference classification of pulmonary tuberculosis. Using this dataset, we first retrospectively evaluated the performance of several existing treatment-decision algorithms. We then used the data to develop two multivariable prediction models that included features used in clinical evaluation of pulmonary tuberculosis-one with chest x-ray features and one without-and we investigated each model's generalisability using internal-external cross-validation. The parameter coefficient estimates of the two models were scaled into two scoring systems to classify tuberculosis with a prespecified sensitivity target. The two scoring systems were used to develop two pragmatic, treatment-decision algorithms for use in primary health-care settings. FINDINGS: Of 4718 children from 13 studies from 12 countries, 1811 (38·4%) were classified as having pulmonary tuberculosis: 541 (29·9%) bacteriologically confirmed and 1270 (70·1%) unconfirmed. Existing treatment-decision algorithms had highly variable diagnostic performance. The scoring system derived from the prediction model that included clinical features and features from chest x-ray had a combined sensitivity of 0·86 [95% CI 0·68-0·94] and specificity of 0·37 [0·15-0·66] against a composite reference standard. The scoring system derived from the model that included only clinical features had a combined sensitivity of 0·84 [95% CI 0·66-0·93] and specificity of 0·30 [0·13-0·56] against a composite reference standard. The scoring system from each model was placed after triage steps, including assessment of illness acuity and risk of poor tuberculosis-related outcomes, to develop treatment-decision algorithms. INTERPRETATION: We adopted an evidence-based approach to develop pragmatic algorithms to guide tuberculosis treatment decisions in children, irrespective of the resources locally available. This approach will empower health workers in primary health-care settings with high tuberculosis incidence and limited resources to initiate tuberculosis treatment in children to improve access to care and reduce tuberculosis-related mortality. These algorithms have been included in the operational handbook accompanying the latest WHO guidelines on the management of tuberculosis in children and adolescents. Future prospective evaluation of algorithms, including those developed in this work, is necessary to investigate clinical performance. FUNDING: WHO, US National Institutes of Health.

Experiences of conditional and unconditional cash transfers intended for improving health outcomes and health service use: a qualitative evidence synthesis.

BACKGROUND: It is well known that poverty is associated with ill health and that ill health can result in direct and indirect costs that can perpetuate poverty. Social protection, which includes policies and programmes intended to prevent and reduce poverty in times of ill health, could be one way to break this vicious cycle. Social protection, particularly cash transfers, also has the potential to promote healthier behaviours, including healthcare seeking. Although social protection, particularly conditional and unconditional cash transfers, has been widely studied, it is not well known how recipients experience social protection interventions, and what unintended effects such interventions can cause.   OBJECTIVES: The aim of this review was to explore how conditional and unconditional cash transfer social protection interventions with a health outcome are experienced and perceived by their recipients.  SEARCH METHODS: We searched Epistemonikos, MEDLINE, CINAHL, Social Services Abstracts, Global Index Medicus, Scopus, AnthroSource and EconLit from the start of the database to 5 June 2020. We combined this with reference checking, citation searching, grey literature and contact with authors to identify additional studies. We reran all strategies in July 2022, and the new studies are awaiting classification. SELECTION CRITERIA: We included primary studies, using qualitative methods or mixed-methods studies with qualitative research reporting on recipients' experiences of cash transfer interventions where health outcomes were evaluated. Recipients could be adult patients of healthcare services, the general adult population as recipients of cash targeted at themselves or directed at children. Studies could be evaluated on any mental or physical health condition or cash transfer mechanism. Studies could come from any country and be in any language. Two authors independently selected studies.  DATA COLLECTION AND ANALYSIS: We used a multi-step purposive sampling framework for selecting studies, starting with geographical representation, followed by health condition, and richness of data. Key data were extracted by the authors into Excel. Methodological limitations were assessed independently using the Critical Appraisal Skills Programme (CASP) criteria by two authors. Data were synthesised using meta-ethnography, and confidence in findings was assessed using the Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) approach.  MAIN RESULTS: We included 127 studies in the review and sampled 41 of these studies for our analysis. Thirty-two further studies were found after the updated search on 5 July 2022 and are awaiting classification. The sampled studies were from 24 different countries: 17 studies were from the African region, seven were from the region of the Americas, seven were from the European region, six were from the South-East Asian region, three from the Western Pacific region and one study was multiregional, covering both the African and the Eastern Mediterranean regions. These studies primarily explored the views and experiences of cash transfer recipients with different health conditions, such as infectious diseases, disabilities and long-term illnesses, sexual and reproductive health, and maternal and child health. Our GRADE-CERQual assessment indicated we had mainly moderate- and high-confidence findings. We found that recipients perceived the cash transfers as necessary and helpful for immediate needs and, in some cases, helpful for longer-term benefits. However, across conditional and unconditional programmes, recipients often felt that the amount given was too little in relation to their total needs. They also felt that the cash alone was not enough to change their behaviour and, to change behaviour, additional types of support would be required. The cash transfer was reported to have important effects on empowerment, autonomy and agency, but also in some settings, recipients experienced pressure from family or programme staff on cash usage. The cash transfer was reported to improve social cohesion and reduce intrahousehold tension. However, in settings where some received the cash and others did not, the lack of an equal approach caused tension, suspicion and conflict. Recipients also reported stigma in terms of cash transfer programme assessment processes and eligibility, as well as inappropriate eligibility processes. Across settings, recipients experienced barriers in accessing the cash transfer programme, and some refused or were hesitant to receive the cash. Some recipients found cash transfer programmes more acceptable when they agreed with the programme's goals and processes.   AUTHORS' CONCLUSIONS: Our findings highlight the impact of the sociocultural context on the functioning and interaction between the individual, family and cash transfer programmes. Even where the goals of a cash transfer programme are explicitly health-related, the outcomes may be far broader than health alone and may include, for example, reduced stigma, empowerment and increased agency of the individual. When measuring programme outcomes, therefore, these broader impacts could be considered for understanding the health and well-being benefits of cash transfers.

Tuberculosis in older adults: case studies from four countries with rapidly ageing populations in the western pacific region.

BACKGROUND: The Western Pacific Region has one of the fastest-growing populations of older adults (≥ 65 years) globally, among whom tuberculosis (TB) poses a particular concern. This study reports country case studies from China, Japan, the Republic of Korea, and Singapore reflecting on their experiences in managing TB among older adults. FINDINGS: Across all four countries, TB case notification and incidence rates were highest among older adults, but clinical and public health guidance focused on this population was limited. Individual country reports illustrated a range of practices and challenges. Passive case finding remains the norm, with limited active case finding (ACF) programs implemented in China, Japan, and the Republic of Korea. Different approaches have been trialled to assist older adults in securing an early diagnosis, as well as adhering to their TB treatment. All countries emphasised the need for person-centred approaches that include the creative application of new technology and tailored incentive programs, as well as reconceptualisation of how we provide treatment support. The use of traditional medicines was found to be culturally entrenched among older adults, with a need for careful consideration of their complementary use. TB infection testing and the provision of TB preventive treatment (TPT) were underutilised with highly variable practice. CONCLUSION: Older adults require specific consideration in TB response policies, given the burgeoning aging population and their high TB risk. Policymakers, TB programs and funders must invest in and develop locally contextualised practice guidelines to inform evidence-based TB prevention and care practices for older adults.

Tuberculosis care models for children and adolescents: a scoping review.

Objective: To map which tuberculosis care models are best suited for children and adolescents. Methods: We conducted a scoping review to assess the impact of decentralized, integrated and family-centred care on child and adolescent tuberculosis-related outcomes, describe approaches for these care models and identify key knowledge gaps. We searched seven literature databases on 5 February 2021 (updated 16 February 2022), searched the references of 18 published reviews and requested data from ongoing studies. We included studies from countries with a high tuberculosis burden that used a care model of interest and reported tuberculosis diagnostic, treatment or prevention outcomes for an age group < 20 years old. Findings: We identified 28 studies with a comparator group for the impact assessment and added 19 non-comparative studies to a qualitative analysis of care delivery approaches. Approaches included strengthening capacity in primary-level facilities, providing services in communities, screening for tuberculosis in other health services, co-locating tuberculosis and human immunodeficiency virus treatment, offering a choice of treatment location and providing social or economic support. Strengthening both decentralized diagnostic services and community linkages led to one-to-sevenfold increases in case detection across nine studies and improved prevention outcomes. We identified only five comparative studies on integrated or family-centred care, but 11 non-comparative studies reported successful treatment outcomes for at least 71% of children and adolescents. Conclusion: Strengthening decentralized services in facilities and communities can improve tuberculosis outcomes for children and adolescents. Further research is needed to identify optimal integrated and family-centred care approaches.

European Respiratory Society International Congress 2021: highlights from best-abstract awardees.

This article provides an overview of some of the highlights of the @EuroRespSoc Congress 2021 from the perspective of the best-abstract awardees of the ERS Assemblies @EarlyCareerERS @OrphaLung https://bit.ly/3JCjHYS.

Xpert MTB/RIF Ultra assay for tuberculosis disease and rifampicin resistance in children.

BACKGROUND: Every year, an estimated one million children and young adolescents become ill with tuberculosis, and around 226,000 of those children die. Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that simultaneously detects Mycobacterium tuberculosis complex and rifampicin resistance. We previously published a Cochrane Review 'Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for tuberculosis disease and rifampicin resistance in children'. The current review updates evidence on the diagnostic accuracy of Xpert Ultra in children presumed to have tuberculosis disease. Parts of this review update informed the 2022 WHO updated guidance on management of tuberculosis in children and adolescents. OBJECTIVES: To assess the diagnostic accuracy of Xpert Ultra for detecting: pulmonary tuberculosis, tuberculous meningitis, lymph node tuberculosis, and rifampicin resistance, in children with presumed tuberculosis. Secondary objectives To investigate potential sources of heterogeneity in accuracy estimates. For detection of tuberculosis, we considered age, comorbidity (HIV, severe pneumonia, and severe malnutrition), and specimen type as potential sources. To summarize the frequency of Xpert Ultra trace results. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, three other databases, and three trial registers without language restrictions to 9 March 2021. SELECTION CRITERIA: Cross-sectional and cohort studies and randomized trials that evaluated Xpert Ultra in HIV-positive and HIV-negative children under 15 years of age. We included ongoing studies that helped us address the review objectives. We included studies evaluating sputum, gastric, stool, or nasopharyngeal specimens (pulmonary tuberculosis), cerebrospinal fluid (tuberculous meningitis), and fine needle aspirate or surgical biopsy tissue (lymph node tuberculosis). For detecting tuberculosis, reference standards were microbiological (culture) or composite reference standard; for stool, we also included Xpert Ultra performed on a routine respiratory specimen. For detecting rifampicin resistance, reference standards were drug susceptibility testing or MTBDRplus. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and, using QUADAS-2, assessed methodological quality judging risk of bias separately for each target condition and reference standard. For each target condition, we used the bivariate model to estimate summary sensitivity and specificity with 95% confidence intervals (CIs). We stratified all analyses by type of reference standard. We summarized the frequency of Xpert Ultra trace results; trace represents detection of a very low quantity of Mycobacterium tuberculosis DNA. We assessed certainty of evidence using GRADE. MAIN RESULTS: We identified 14 studies (11 new studies since the previous review). For detection of pulmonary tuberculosis, 335 data sets (25,937 participants) were available for analysis. We did not identify any studies that evaluated Xpert Ultra accuracy for tuberculous meningitis or lymph node tuberculosis. Three studies evaluated Xpert Ultra for detection of rifampicin resistance. Ten studies (71%) took place in countries with a high tuberculosis burden based on WHO classification. Overall, risk of bias was low. Detection of pulmonary tuberculosis Sputum, 5 studies Xpert Ultra summary sensitivity verified by culture was 75.3% (95% CI 64.3 to 83.8; 127 participants; high-certainty evidence), and specificity was 97.1% (95% CI 94.7 to 98.5; 1054 participants; high-certainty evidence). Gastric aspirate, 7 studies Xpert Ultra summary sensitivity verified by culture was 70.4% (95% CI 53.9 to 82.9; 120 participants; moderate-certainty evidence), and specificity was 94.1% (95% CI 84.8 to 97.8; 870 participants; moderate-certainty evidence). Stool, 6 studies Xpert Ultra summary sensitivity verified by culture was 56.1% (95% CI 39.1 to 71.7; 200 participants; moderate-certainty evidence), and specificity was 98.0% (95% CI 93.3 to 99.4; 1232 participants; high certainty-evidence). Nasopharyngeal aspirate, 4 studies Xpert Ultra summary sensitivity verified by culture was 43.7% (95% CI 26.7 to 62.2; 46 participants; very low-certainty evidence), and specificity was 97.5% (95% CI 93.6 to 99.0; 489 participants; high-certainty evidence). Xpert Ultra sensitivity was lower against a composite than a culture reference standard for all specimen types other than nasopharyngeal aspirate, while specificity was similar against both reference standards. Interpretation of results In theory, for a population of 1000 children: • where 100 have pulmonary tuberculosis in sputum (by culture): - 101 would be Xpert Ultra-positive, and of these, 26 (26%) would not have pulmonary tuberculosis (false positive); and - 899 would be Xpert Ultra-negative, and of these, 25 (3%) would have tuberculosis (false negative). • where 100 have pulmonary tuberculosis in gastric aspirate (by culture): - 123 would be Xpert Ultra-positive, and of these, 53 (43%) would not have pulmonary tuberculosis (false positive); and - 877 would be Xpert Ultra-negative, and of these, 30 (3%) would have tuberculosis (false negative). • where 100 have pulmonary tuberculosis in stool (by culture): - 74 would be Xpert Ultra-positive, and of these, 18 (24%) would not have pulmonary tuberculosis (false positive); and - 926 would be Xpert Ultra-negative, and of these, 44 (5%) would have tuberculosis (false negative). • where 100 have pulmonary tuberculosis in nasopharyngeal aspirate (by culture): - 66 would be Xpert Ultra-positive, and of these, 22 (33%) would not have pulmonary tuberculosis (false positive); and - 934 would be Xpert Ultra-negative, and of these, 56 (6%) would have tuberculosis (false negative). Detection of rifampicin resistance Xpert Ultra sensitivity was 100% (3 studies, 3 participants; very low-certainty evidence), and specificity range was 97% to 100% (3 studies, 128 participants; low-certainty evidence). Trace results Xpert Ultra trace results, regarded as positive in children by WHO standards, were common. Xpert Ultra specificity remained high in children, despite the frequency of trace results. AUTHORS' CONCLUSIONS: We found Xpert Ultra sensitivity to vary by specimen type, with sputum having the highest sensitivity, followed by gastric aspirate and stool. Nasopharyngeal aspirate had the lowest sensitivity. Xpert Ultra specificity was high against both microbiological and composite reference standards. However, the evidence base is still limited, and findings may be imprecise and vary by study setting. Although we found Xpert Ultra accurate for detection of rifampicin resistance, results were based on a very small number of studies that included only three children with rifampicin resistance. Therefore, findings should be interpreted with caution. Our findings provide support for the use of Xpert Ultra as an initial rapid molecular diagnostic in children being evaluated for tuberculosis.

Patient and health-care provider experience of a person-centred, multidisciplinary, psychosocial support and harm reduction programme for patients with harmful use of alcohol and drug-resistant tuberculosis in Minsk, Belarus.

BACKGROUND: Tuberculosis (TB) often concentrates in groups of people with complex health and social issues, including alcohol use disorders (AUD). Risk of TB, and poor TB treatment outcomes, are substantially elevated in people who have AUD. Médecins sans Frontières and the Belarus Ministry of Health have worked to improve treatment adherence in patients with multi-drug or rifampicin resistant (MDR/RR)-TB and harmful use of alcohol. In 2016, a person-centred, multidisciplinary, psychosocial support and harm reduction programme delivered by TB doctors, counsellors, psychiatrists, health-educators, and social workers was initiated. In 2020, we described patient and provider experiences within the programme as part of a wider evaluation. METHODS: We recruited 12 patients and 20 health-care workers, using purposive sampling, for in-depth individual interviews and focus group discussions. We used a participant-led, flexible, exploratory approach, enabling participants and the interviewer to shape topics of conversation. Qualitative data were coded manually and analysed thematically. As part of the analysis process, identified themes were shared with health-care worker participants to enable their reflections to be incorporated into the findings. RESULTS: Key themes related to the patients' and practitioners experience of having and treating MDRTB with associated complex health and social issues were: fragility and despair and guidance, trust and health. Prejudice and marginalisation were global to both themes. Counsellors and other health workers built a trusting relationship with patients, enabling guidance through a multi-disciplinary approach, which supported patients to achieve their vision of health. This guidance was achieved by a team of social workers, counsellors, doctors and health-educators who provided professional and individualised help for patients' illnesses, personal or interpersonal problems, administrative tasks, and job searches. CONCLUSIONS: Patients with MDR/RR-TB and harmful use of alcohol faced complex issues during treatment. Our findings describe how person-centred, multi-disciplinary, psychosocial support helped patients in this setting to cope with these challenges and complete the treatment programme. We recommend that these findings are used to: i) inform programmatic changes to further boost the person-centred care nature of this program; and ii) advocate for this type of person-centred care approach to be rolled out across Belarus, and in contexts that face similar challenges.

Comparative Effectiveness of Regimens for Drug-Susceptible Tuberculous Meningitis in Children and Adolescents: A Systematic Review and Aggregate-Level Data Meta-Analysis.

Background: Before August 2021, the only regimen recommended by the World Health Organization (WHO) to treat pediatric drug-susceptible tuberculous meningitis was a 12-month regimen consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide (2HRZE/10HR). The comparative effectiveness of shorter regimens is unknown. Methods: To inform a WHO guideline update, we undertook a systematic review and meta-analysis to evaluate outcomes from regimens of 6- to less than 12-months' duration that included, at a minimum, isoniazid, rifampicin, and pyrazinamide. We included studies that applied rigorous diagnostic criteria and reported outcomes for ≥10 children or adolescents. Using generalized linear mixed models, we estimated the random effects pooled proportions of patients with key outcomes. Results: Of 7 included studies, none compared regimens head-to-head. Three studies (724 patients) used a 6-month intensive regimen, which includes isoniazid and rifampicin at higher doses, pyrazinamide, and ethionamide instead of ethambutol (6HRZEto). Outcomes for this versus the 12-month regimen (282 patients, 3 studies) were, respectively, as follows: death, 5.5% (95% confidence interval [CI], 2.1%-13.4%) vs 23.9% (95% CI, 17.5%-31.7%); treatment success (survival with or without sequelae), 94.6% (95% CI, 73.9%-99.1%) vs 75.4% (95% CI, 68.7%-81.1%); and neurological sequelae among survivors, 66.0% (95% CI, 55.3%-75.3%) vs 36.3% (95% CI, 30.1%-43.0%). Relapse did not occur among 148 patients followed-up for 2 years after completing the 6-month intensive regimen. Conclusions: Our findings are limited by the small number of studies and substantial potential for confounding. Nonetheless, the 6HRZEto regimen was associated with high treatment success and is now recommended by WHO as an alternative to the 12-month regimen.

Inappropriate supply of antibiotics for common viral infections by community pharmacies in Vietnam: A standardised patient survey.

Background: This study aimed to evaluate the appropriateness of antibiotic dispensing of private pharmacies in Vietnam. Methods: Standardised patient surveys were conducted in randomly selected community pharmacies across 40 districts in Vietnam. Four clinical scenarios were represented by patient actors: (a) an adult requesting treatment for a sibling with a viral upper respiratory tract infection (URTI), (b) a parent requesting treatment for a child with acute diarrhoea, (c) an adult making a direct antibiotic request, and (d) an adult presenting with an antibiotic prescription. We calculated the proportion of interactions that resulted in inappropriate supply of antibiotics and patient advice. Predictors of inappropriate antibiotic supply were assessed. Findings: Patient actors attended 949 pharmacies, resulting in 1266 clinical interactions. Antibiotics were inappropriately supplied to 92% (291/316) of adults requesting treatment for URTI symptoms, 43% (135/316) for children with acute diarrhoea symptoms and to 84% (267/317) of direct request for antibiotics. Only 49% of pharmacies advised patients regarding their antibiotic use. Female actors were more likely to be given antibiotics than male actors for URTI (aOR 2·71, 1·12-6·60) but not for diarrhoeal disease. Pharmacies in northern Vietnam were more likely than those in southern Vietnam to supply antibiotics without a prescription: for adult URTI (aOR=5·8, 95% CI: 2·2-14·9) and childhood diarrhoea (aOR=3·5, 95% CI: 2·0-6·0) symptoms, but less likely to dispense for direct antibiotics request. Interpretation: Inappropriate antibiotic supply was common in Vietnamese private pharmacies. Multifaceted measures are urgently needed to achieve WHO's global action plan for the optimal use of antimicrobials. Funding: This study was funded by a grant from the Australian Department of Foreign Affairs and Trade.

Symptom- and chest-radiography screening for active pulmonary tuberculosis in HIV-negative adults and adults with unknown HIV status.

BACKGROUND: Systematic screening in high-burden settings is recommended as a strategy for early detection of pulmonary tuberculosis disease, reducing mortality, morbidity and transmission, and improving equity in access to care. Questioning for symptoms and chest radiography (CXR) have historically been the most widely available tools to screen for tuberculosis disease. Their accuracy is important for the design of tuberculosis screening programmes and determines, in combination with the accuracy of confirmatory diagnostic tests, the yield of a screening programme and the burden on individuals and the health service. OBJECTIVES: To assess the sensitivity and specificity of questioning for the presence of one or more tuberculosis symptoms or symptom combinations, CXR, and combinations of these as screening tools for detecting bacteriologically confirmed pulmonary tuberculosis disease in HIV-negative adults and adults with unknown HIV status who are considered eligible for systematic screening for tuberculosis disease. Second, to investigate sources of heterogeneity, especially in relation to regional, epidemiological, and demographic characteristics of the study populations. SEARCH METHODS: We searched the MEDLINE, Embase, LILACS, and HTA (Health Technology Assessment) databases using pre-specified search terms and consulted experts for unpublished reports, for the period 1992 to 2018. The search date was 10 December 2018. This search was repeated on 2 July 2021. SELECTION CRITERIA: Studies were eligible if participants were screened for tuberculosis disease using symptom questions, or abnormalities on CXR, or both, and were offered confirmatory testing with a reference standard. We included studies if diagnostic two-by-two tables could be generated for one or more index tests, even if not all participants were subjected to a microbacteriological reference standard. We excluded studies evaluating self-reporting of symptoms. DATA COLLECTION AND ANALYSIS: We categorized symptom and CXR index tests according to commonly used definitions. We assessed the methodological quality of included studies using the QUADAS-2 instrument. We examined the forest plots and receiver operating characteristic plots visually for heterogeneity. We estimated summary sensitivities and specificities (and 95% confidence intervals (CI)) for each index test using bivariate random-effects methods. We analyzed potential sources of heterogeneity in a hierarchical mixed-model. MAIN RESULTS: The electronic database search identified 9473 titles and abstracts. Through expert consultation, we identified 31 reports on national tuberculosis prevalence surveys as eligible (of which eight were already captured in the search of the electronic databases), and we identified 957 potentially relevant articles through reference checking. After removal of duplicates, we assessed 10,415 titles and abstracts, of which we identified 430 (4%) for full text review, whereafter we excluded 364 articles. In total, 66 articles provided data on 59 studies. We assessed the 2 July 2021 search results; seven studies were potentially eligible but would make no material difference to the review findings or grading of the evidence, and were not added in this edition of the review. We judged most studies at high risk of bias in one or more domains, most commonly because of incorporation bias and verification bias. We judged applicability concerns low in more than 80% of studies in all three domains. The three most common symptom index tests, cough for two or more weeks (41 studies), any cough (21 studies), and any tuberculosis symptom (29 studies), showed a summary sensitivity of 42.1% (95% CI 36.6% to 47.7%), 51.3% (95% CI 42.8% to 59.7%), and 70.6% (95% CI 61.7% to 78.2%, all very low-certainty evidence), and a specificity of 94.4% (95% CI 92.6% to 95.8%, high-certainty evidence), 87.6% (95% CI 81.6% to 91.8%, low-certainty evidence), and 65.1% (95% CI 53.3% to 75.4%, low-certainty evidence), respectively. The data on symptom index tests were more heterogenous than those for CXR. The studies on any tuberculosis symptom were the most heterogeneous, but had the lowest number of variables explaining this variation. Symptom index tests also showed regional variation. The summary sensitivity of any CXR abnormality (23 studies) was 94.7% (95% CI 92.2% to 96.4%, very low-certainty evidence) and 84.8% (95% CI 76.7% to 90.4%, low-certainty evidence) for CXR abnormalities suggestive of tuberculosis (19 studies), and specificity was 89.1% (95% CI 85.6% to 91.8%, low-certainty evidence) and 95.6% (95% CI 92.6% to 97.4%, high-certainty evidence), respectively. Sensitivity was more heterogenous than specificity, and could be explained by regional variation. The addition of cough for two or more weeks, whether to any (pulmonary) CXR abnormality or to CXR abnormalities suggestive of tuberculosis, resulted in a summary sensitivity and specificity of 99.2% (95% CI 96.8% to 99.8%) and 84.9% (95% CI 81.2% to 88.1%) (15 studies; certainty of evidence not assessed). AUTHORS' CONCLUSIONS: The summary estimates of the symptom and CXR index tests may inform the choice of screening and diagnostic algorithms in any given setting or country where screening for tuberculosis is being implemented. The high sensitivity of CXR index tests, with or without symptom questions in parallel, suggests a high yield of persons with tuberculosis disease. However, additional considerations will determine the design of screening and diagnostic algorithms, such as the availability and accessibility of CXR facilities or the resources to fund them, and the need for more or fewer diagnostic tests to confirm the diagnosis (depending on screening test specificity), which also has resource implications. These review findings should be interpreted with caution due to methodological limitations in the included studies and regional variation in sensitivity and specificity. The sensitivity and specificity of an index test in a specific setting cannot be predicted with great precision due to heterogeneity. This should be borne in mind when planning for and implementing tuberculosis screening programmes.

Addressing the Data Gaps on Child and Adolescent Tuberculosis.

The burden of tuberculosis (TB) among children and young adolescents (<15 years old) is estimated at 1.1 million; however, only 400,000 are treated for TB, indicating a large gap between the number who are cared for and the number estimated to have TB. Accurate data on the burden of pediatric TB is essential to guide action. Despite several improvements in estimating the burden of pediatric TB in the last decade, as well as enhanced data collection efforts, several data gaps remain, both at the global level, but also at the national level where surveillance systems and collaborative research are critical. In this article, we describe recent advances in data collection and burden estimates for TB among children and adolescents, and the remaining gaps. While data collection continues to improve, burden estimates must evolve in parallel, both in terms of their frequency and the methods used. Currently, at the global level, there is a focus on age-disaggregation of TB notifications, the collection of data on TB-HIV, multi-drug resistant (MDR)-TB and treatment outcomes, as well as estimates of the disease burden. Additional data from national surveillance systems or research projects on TB meningitis, as well as other forms of extra-pulmonary TB, would be useful. We must capitalize on the current momentum in child and adolescent TB to close the remaining data gaps for these age groups to better understand the epidemic and further reduce morbidity and mortality due to TB.

Adaptation and validation of the Van Rie tuberculosis stigma scale in Vietnam.

OBJECTIVES: Tuberculosis (TB) stigma contributes to diagnostic delay, disease concealment, and reduced wellbeing for affected individuals. Despite the availability of several TB stigma scales, most high-TB burden countries do not have a culturally validated version available. This study evaluated the Van Rie TB stigma scale (VTSS) among people with TB in Vietnam. METHODS: This study consisted of two phases. In phase 1, the VTSS was culturally and linguistically adapted to the Vietnamese context. In phase 2, people with TB were invited to complete a survey containing the VTSS, a depression scale, and a quality of life scale. The data analysis included confirmatory factor analysis (CFA), exploratory factor analysis (EFA), construct validity, and floor or ceiling effects. RESULTS: In phase 1, items were reworded from the third person to the first person. The TB/HIV co-infection items (items 7 and 11) were the least relevant for people with TB (62% and 73% relevance, respectively). In phase 2, the CFA demonstrated adequate goodness-of-fit indices (GFI = 0.88, CFI = 0.96, RMSEA = 0.058); however several of the item factor loadings were low. The EFA demonstrated good internal consistency (α = 0.85) and revealed one dominant factor. Construct validity was low. CONCLUSIONS: The VTSS demonstrated good psychometric properties in Vietnam. Depending on the purpose of the scale, the HIV co-infection items and item 10 could be considered for removal.

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.