BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE. METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards. RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitivity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research. CONCLUSION: These standards provide a person-centred, consensus-based approach to minimise the impact of AE during TB treatment.

Clinical standards for the management of adverse effects during treatment for TB

Tuberculosis (TB) is the world's leading cause of infectious disease-related mortality, apart from COVID-19 presently [1]. Standard TB treatment for drug-susceptible (DS) TB takes 6–9 months and requires daily intake of multiple medications [1]. Notably, proper treatment adherence is essential for successful treatment outcome [1, 2]. To improve adherence, counselling and education are important. Digital adherence technology in combination with therapeutic drug monitoring could aid in supporting adherence and personalising dosing while at the same time supporting patients to carry out TB medication related tasks independently https://bit.ly/3gh1A1c

Combining digital adherence technology and therapeutic drug monitoring for personalised tuberculosis care

Respiratory health has become a prevailing priority amid the diverse global health challenges that the 21st century brings, due to its substantial impact on individuals and communities on a global scale. Due to rapid advances in medicine, emerging knowledge gaps appear along with new challenges and ethical considerations. While breakthroughs in medical science can bring about encouraging possibilities for better treatments and interventions, they also lead to unanswered questions and areas where further research is warranted. A PubMed search on the topic “global respiratory health priorities” between the years 2000 and 2023 was conducted, which returned 236 articles. Of these, 55 were relevant and selected for inclusion in this article. The selection process took into account literature reviews, opinions from expert groups and careful analysis of existing gaps and challenges within the field; our selection encompasses specific infectious and noninfectious respiratory conditions in both adults and children. The global respiratory health priorities identified were selected on the basis that they have been recognised as critical areas of investigation and potential advancement and they span across clinical, translational, epidemiological and population health domains. Implementing these priorities will require a commitment to fostering collaboration and knowledge-sharing among experts in different fields with the ultimate aim to improve respiratory health outcomes for individuals and communities alike.

Global respiratory health priorities at the beginning of the 21st century

Abstract Optimal diagnosis and management of children aged &lt;15 y with rifampicin- or multidrug-resistant tuberculosis (RR/MDR-TB) relies on identification of adults with the disease and pro-active screening of their close contacts. Children may be diagnosed with RR/MDR-TB based on microbiological confirmation from clinical specimens (sputum, gastric washings, stool), but usually the diagnosis is presumptive, with a history of exposure to RR/MDR-TB and clinical/radiological signs and symptoms suggestive of TB disease. RR/MDR-TB should also be considered in children where first-line TB treatment fails despite good adherence to therapy. Composition and duration of all-oral RR/MDR-TB treatment regimens in children are based on site and severity of TB disease, drug resistance profile of the Mycobacterium tuberculosis strain (isolated from the child or from the most likely source patient), inclusion of at least four drugs considered to be effective (with priority given to World Health Organization Group A and B drugs), toxicity and tolerability of medications (and feasibility of adverse effect monitoring in the child’s setting), and availability of child-friendly formulations of TB medications. Individualized RR/MDR-TB regimens are preferable to the standardised 9–12-mo regimen for children, and injectable agents must not be used. Optimal adherence to treatment relies on education, training and support for caregivers and others who are responsible for administering medications to children, as well as close clinical monitoring and early management of adverse effects. Children who are initiated on adequate RR/MDR-TB regimens have high treatment success rates, but efforts to find and treat more children with undiagnosed RR/MDR-TB are crucial to reduce childhood TB mortality. 

Current Treatment of Drug-Resistant Tuberculosis in Children.

Abstract Heart failure (HF) and cirrhosis are frequently associated with pleural effusions (PEs). Despite their apparently benign nature, both HF-related effusions and hepatic hydrothorax (HH) have poor prognosis because they represent an advanced stage of the disease. Optimization of medical therapy in these two entities involve not only the use of diuretics, but also other pharmacological therapies. For instance, all HF patients with reduced or mildly reduced left ventricular ejection fraction can benefit from angiotensin receptor–neprilysin inhibitors, beta blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors. Conversely, it is better for HH patients to avoid nonselective beta blockers. Refractory cardiac- and cirrhosis-related PEs are commonly managed by iterative therapeutic thoracentesis. When repeated aspirations are needed, thereby diminishing quality of life, the insertion of an indwelling pleural catheter (IPC) may be warranted. However, in selected HH patients who are diuretic-resistant or diuretic-intractable, placement of transjugular intrahepatic portosystemic shunts should be considered as a bridge to liver transplantation, whereas in transplant candidates the role of IPC is debatable. Another benign condition, pleural tuberculosis (TB) is a serious health problem in developing countries. Diagnostic certainty is still a concern due to the paucibacillary nature of the infection, although the use of more sensitive nucleic acid amplification tests is becoming more widespread. Its treatment is the same as that of pulmonary TB, but the potential drug interactions between antiretroviral and anti-TB drugs in HIV-coinfected patients as well as the current recommended guidelines for the different types of anti-TB drugs resistance should be followed.

Expert Review on Contemporary Management of Common Benign Pleural Effusions

SUMMARY BACKGROUND: The aim of these clinical standards is to provide guidance on ‘best practice’ for diagnosis, treatment and management of drug-susceptible pulmonary TB (PTB). METHODS: A panel of 54 global experts in the field of TB care, public health, microbiology, and pharmacology were identified; 46 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all 46 participants. RESULTS: Seven clinical standards were defined: Standard 1, all patients (adult or child) who have symptoms and signs compatible with PTB should undergo investigations to reach a diagnosis; Standard 2, adequate bacteriological tests should be conducted to exclude drug-resistant TB; Standard 3, an appropriate regimen recommended by WHO and national guidelines for the treatment of PTB should be identified; Standard 4, health education and counselling should be provided for each patient starting treatment; Standard 5, treatment monitoring should be conducted to assess adherence, follow patient progress, identify and manage adverse events, and detect development of resistance; Standard 6, a recommended series of patient examinations should be performed at the end of treatment; Standard 7, necessary public health actions should be conducted for each patient. We also identified priorities for future research into PTB. CONCLUSION: These consensus-based clinical standards will help to improve patient care by guiding clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment for PTB.

Clinical standards for drug-susceptible pulmonary TB

<h3>Background</h3> Rapid detection of resistance to key drugs such as fluoroquinolones (FQ) and bedaquiline (BDQ) is essential for appropriate management of multi-drug resistant tuberculosis (MDR-TB). . Molecular tests available require either infrastructures not available in peripheral laboratories in low resource countries, or do not detect resistance to BDQ. Recently, two tests have been developed: GeneXpert MTB/XDR (Cepheid, USA) detecting resistance to isoniazid (INH), FQ and ethionamide (ETH), and TrueNat XDR (Molbio Diagnostics, India) for detection of resistance to INH, FQ and BDQ. <h3>Methods</h3> In the EDCTP-funded project (DIAMA) aimed at developing culture free approaches for diagnosis and management of MDR-TB patients, we assessed the performances of these tests in field conditions compared to phenotypic drug-susceptibility testing (pDST) and whole genome sequencing (WGS) using 1711 unique samples consecutively collected in the Sub-Saharan African region (Benin, Cameroon, DRC, Ethiopia, Guinea, Mali, Nigeria, Rwanda and Senegal). <h3>Results</h3> Using a composite reference standard comprising pDST and WGS, Xpert-XDR showed a sensitivity of 87.3% for INH, 37.8% for ETH and 66.7% for FQ, with a respective specificity of 96.5%, 98.3% and 99.7%. For TrueNat, the sensitivity was 88.1% for INH and 47.4% for FQ, with a specificity of 85.7% for INH, 97.7% for FQ and 98.5% for BDQ. <h3>Conclusion</h3> These tests showed promising results, particularly as screening test for detection of resistance to FQ and BDQ. 

OA-484 Improving rapid detection of 2nd line drug resistance in Mycobacterium tuberculosis with Xpert MTB/XDR and MolBio 2nd line

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Clinical standards for drug-susceptible pulmonary TB

OA-484 Improving rapid detection of 2nd line drug resistance in Mycobacterium tuberculosis with Xpert MTB/XDR and MolBio 2nd line