SHINE (Shorter Treatment for Minimal Tuberculosis in Children) was the first Phase 3 paediatric TB treatment-shortening trial. Robust chest X-ray (CXR) classification methods were integral to excluding severe disease for trial eligibility and to retrospectively adjudicating TB status at baseline. We describe and critically evaluate the CXR classification approaches and processes used in the SHINE trial.Children with non-severe TB were randomised to 4- vs 6-months anti-TB treatment. Radiologically non-severe TB was defined on CXR. CXRs were systematically interpreted by on-site clinicians prospectively for eligibility determination and retrospectively by experts to inform adjudication of baseline TB status and disease severity.A screening CXR was successfully obtained from all 1,204 enrolled children; 1,134 CXRs from children with intra-thoracic TB were reviewed by expert readers. Compared with the expert panel, enrolling clinicians classified more CXRs as abnormal and 'typical TB' and all as radiologically non-severe. The expert panel retrospectively classified 71/1,134 (6%) CXRs as severe. Of these, 4 (5.6%) had unfavourable outcomes compared with 34 (3.0%) in the trial overall.Using CXRs to classify radiological disease severity and inform eligibility decisions in real-time by local enrolling clinicians was feasible and safe in this large paediatric TB trial. Retrospective central expert CXR review was successful. Refinement of the CXR methods for the classification of both disease severity and TB status could support standardised implementation in routine care and research..

Understanding factors associated with increased risk for tuberculosis (TB) recurrence is essential in lowering the TB burden. We aimed to quantify the burden, risk factors, and timing of TB presumptive recurrence.We analyzed test results from 2013 to 2017 in the South African National Health Laboratory Service's database. We defined a person's TB episode to start with their first positive TB test. In the absence of treatment outcome data, we assumed the episode concluded 6 months later for rifampicin-susceptible TB (RS-TB) and 18 months later for rifampicin-resistant TB (RR-TB), provided that at least one negative smear or culture test was recorded within this period. We defined a presumptive recurrent TB episode to start with a positive TB test after the completion of a prior episode. We calculated recurrence measures stratified by various demographics and RR-TB status.Of 574,316 people with RS-TB, 4.7% experienced at least one presumptive recurrent TB episode. Higher local TB notification rates, HIV coinfection, and males experienced higher recurrence rates. Most (89.4%) of the first RS-TB recurrences occurred within a year of the initial episode.Our findings of when and among whom recurrent TB is more likely to occur can be used to assist early interventions and inform impact on patient care..

Hyponatraemia is associated with morbidity and mortality among various medical disorders. Evidence on the association between hyponatraemia at the time of exacerbation and the prognosis in patients with bronchiectasis is lacking.This was a single-centre retrospective study. We included all bronchiectasis patients who were hospitalised in a regional hospital in Hong Kong for exacerbation from 1 January 2019 to 30 June 2022, to assess the association between hyponatraemia during hospitalised exacerbation and the subsequent outcomes.169 patients were included in this study, of which 46 (27.2%) had hyponatraemia upon admission. Patients in the hyponatraemia group had shorter overall survival (OS) with a median OS of 31.3 months (95% CI 0.76-717.0) in the hyponatraemia group and 104.4 months (95% CI 0.82-1208.3) in the non-hyponatraemia group, adjusted hazard ratio (aHR) of 1.87 (95% CI 1.09-3.20; = 0.023). Patients in the hyponatraemia group also had shorter time-to-next hospitalised bronchiectasis exacerbation with a median time-to-next hospitalised bronchiectasis exacerbation of 72.1 months (95% CI 0.25-362.1) in the hyponatraemia group and 144.6 months (95% CI 1.53-1437.8) in the non-hyponatraemia group, aHR of 2.04 (95% CI 1.07-3.88; = 0.030).This is the first report on the incidence and prognostic value of hyponatraemia in hospitalised bronchiectasis exacerbation, which was observed in 27.2% of patients. It was associated with significantly increased mortality and shorter time-to-next hospitalised bronchiectasis exacerbation when compared with the non-hyponatraemia group..

Understanding the motivations behind clinical trial participation can help enhance recruitment strategies and determine the generalizability of trial results. This study focuses on the reasons for participating in or declining the Tuberculosis Trials Consortium Study 33 (iAdhere), a clinical trial on the treatment of latent tuberculosis infection (LTBI).A quantitative evaluation was conducted among screened patients to ascertain their reasons for participating or not in the iAdhere trial. The study gathered data from enrolled participants and those who chose not to enroll.Among 1,002 enrolled individuals, 290 participants provided 749 reasons for enrolling. The most common reasons included access to shorter treatment regimens (56%), avoiding progression to TB disease (45%), and improving health (21%). Of the 670 eligible persons who chose not to enroll, 551 individuals provided 800 reasons, with the most common being a preference for standard therapy (17%), disinterest in study medication or TB therapy (both 13%), and the inconvenience of daily observed treatment (12%).The desire for shorter treatment options and preventing active disease motivates participation in LTBI trials. The diverse reasons for declining enrolment suggest the importance of developing targeted recruitment strategies. These findings support exploring shorter treatment regimens and can guide future recruitment efforts..

Pleural infection leading to empyema is a severe condition marked by accumulated infected fluid in the pleural space. Pneumonia with parapneumonic effusion is its most common precursor. The global incidence of pleural infections has increased significantly, with existing literature mainly focusing on bacterial empyema, leaving a gap in comparative analyses.A retrospective review was conducted on 561 cases of bacterial, tuberculous, and fungal empyema over a 10-year period. The study compared and analysed overall survival rates, 30-day mortality rates after surgery, and clinical characteristics.The three empyema groups displayed distinct clinical characteristics. Fungal empyema had the worst overall survival compared to bacterial and tuberculous empyema, which had similar survival rates based on 30-day and 2-year mortality. Fungal empyema, advanced age, and high Charlson Comorbidity Index (CCI) score were independent predictors of poor prognosis.Fungal empyema has the highest mortality rate post-decortication surgery. Advanced age and high CCI score are independent predictors of poor prognosis..

Reducing systemic inequities in testing, access to care, social protection - and in the scientific process - is essential to end TB. Incorporating social science methods and expertise on inequity into the mainstream TB response would help ensure that political commitments to equity move beyond symbolic gestures. We convened a meeting between TB social scientists, people with lived experience, civil society and community members to discuss equity within the global TB response. Here, we propose five means by which a social science lens can strengthen equitable, person-centred responses and reconcile the public health significance of TB with the principles of social justice.

Detection of (MTB) in bioaerosols derived from patients with active pulmonary TB is a potential alternative diagnostic method for patients with presumed TB who cannot expectorate sputum.To assess the efficacy of a bioaerosol particle collection method to capture MTB and diagnose TB.A mask-like filter holder (3D mask) with a water-soluble gelatine filter (GF) and one containing a water-insoluble polypropylene filter (PPF) were prepared. Eligible patients wore the 3D mask with GF or PPF within 3 days of starting anti-TB drugs. The GF and PPF filters were collected after 2 and 8 h. DNA was extracted from the filter samples and tested using loop-mediated isothermal amplification (LAMP).Filter samples were collected from 57 and 20 patients with and without active pulmonary TB, respectively. The GF and PPF sensitivity was 76.2% and 83.3%, respectively. The specificity of both methods was 100%. Of the 57 patients diagnosed with non-expectorated sputum samples, including suction phlegm, gastric lavage, and bronchial lavage fluid, 55.6% and 50.0% were positive by GF and PPF, respectively.We present a 3D mask filter sampling method for exhaled bioaerosol particles that can be used in clinical practice to diagnose patients with presumed TB..

Until recently, multidrug-resistant TB (MDR-TB) was treated with lengthy and toxic regimens. New three-drug anti-TB regimens raise the question of whether they are sufficiently active for MDR-TB in Central Asia, an MDR-TB hotspot region.In a cohort of rifampicin-resistant (RR) and MDR-TB patients in the Kyrgyz Republic, we investigated the impact of the number of drugs that were tested susceptible by whole-genome sequencing (WGS) and conventional drug susceptibility testing (DST) and used for treatment on the treatment response, defined as 'matches'. Logistic regressions were performed to assess the effect of having ≥ 4 susceptible drugs in a regimen at baseline and at Month 2 on the treatment response.The study included 227 participants with RR/MDR-TB (30.8% female; median age 30.4 years). The age- and sex-adjusted analysis showed an association between a regimen with ≥ 4 WGS matches at baseline (adjusted odds ratio [aOR] 2.10, 95% CI 1.00-4.41). No association was found when using conventional DST to define matches.Our study confirms that the inclusion of four efficacious anti-TB drugs in an MDR-TB regimen increases the chances of a positive treatment response. Susceptibility of at least four drugs in WGS-DST predicts a positive treatment response..

Treatment outcomes and long-term survival of non-tuberculous mycobacterial pulmonary disease (NTM-PD) in a real-world setting are difficult to assess, especially for species other than complex (MAC).This was a retrospective cohort study on all Croatian residents with respiratory NTM isolates from 2006 to 2015, with follow-up to 2020.Therapy was started in 98/137 (71.5%) of patients, significantly more often in patients with fibrocavitary disease and/or sputum smear positivity. Unsuccessful treatment outcomes were recorded in 39/98 (39.8%) patients (14 deaths and 25 treatment failures). One-year and 5-year all-cause mortality were respectively 18.2% and 37.6%. Guideline-based treatment (GBT) was started in 50/98 (51%) of treated patients and followed for the recommended duration in 35.7% (35/98). This resulted in a higher chance of cure (OR 3.79, 95% CI 1.29 to 11.1; = 0.012) than inadequately treated/untreated patients. For disease, high cure rates (>80%) were achieved both with GBT and non-GBT treatment regimens.Guideline-based therapy resulted in a four-time higher chance of being cured. The impact of GBT on treatment outcomes was clear for MAC disease, but no apparent effect was observed for patients with disease..

TB disproportionately affects poorer, vulnerable people and communities, and has severe social and economic impacts on those affected. However, many countries do not yet include social protection in their programmatic response to TB. Here, we provide a critical perspective on the guidance developed by the WHO and the International Labour Organization (ILO) to help countries implement social protection programmes. The guidance emphasises the need for a multisectoral response to TB, and includes practical information on how to design appropriate social protection programmes that respond to the needs of people affected by TB.

Pesticides are used to control pests, but they are toxic and may severely harm children's health. We assessed health outcomes in Italian children living close to cultivations sprayed with pesticides.In 2011-2012, 2,367 schoolchildren (6-14 years) living in eight Italian cities participated in the Indoor-School observational study. Parents filled in a standardised questionnaire on children's health and related risk factors. Children were classified as exposed to pesticides if living close to cultivations sprayed with pesticides. The association between the last three months of respiratory, allergic or systemic symptoms and pesticide exposure was assessed by multinomial logistic regression models, accounting for host/environmental risk factors.Overall, 14% of children were exposed to pesticides, with significant differences among geographical areas: 21.2% in Northern Italy, 11.6% in Central Italy, and 9.7% in Southern Italy. Pesticide exposure was significantly associated with having: 1) 'often': eye symptoms (OR 3.81, 95% CI 2.06-7.05), skin symptoms (OR 2.60, 95% CI 1.34-5.03), lower airway symptoms (OR 2.38, 95% CI 1.41-4.01), systemic symptoms (OR 1.56, 95% CI 0.96-2.53, borderline); 2) 'daily': upper airways symptoms (OR 2.25, 95% CI 1.25-4.07) and systemic symptoms (OR 2.76, 95% CI 1.43-5.34).Self-reported pesticide exposure was associated with respiratory, allergic or systemic symptoms in children. Public authorities should be aware of and intervene to mitigate this health risk..

More than 10 million individuals develop active TB each year. The diagnosis and treatment of TB create greenhouse gas emissions, contributing to climate change. This study estimates the carbon footprint (CF) of successfully treating one person with drug-susceptible pulmonary TB (DS-PTB) in India.We defined the cascade of care for DS-PTB using national guidelines, interviews, and direct observation. We estimated the inputs for TB diagnosis and treatment in United States dollars, kilowatts per hour, and kilometres travelled; we converted them into carbon dioxide emissions equivalents (CO₂e) using an appropriate calculator.The CF of diagnosing and treating one person with DS-PTB in India is 103.8 kg CO₂e: 31.9% attributable to diagnosis and 68.1% to treatment. Emissions came primarily from first-line drugs (21.2%), hospitalisations (17.4%), and laboratory processes.We conservatively estimate that treating all persons with TB in India would produce at least 290,640 metric tonnes of CO₂e per year, approximately the same emissions as 63,182 passenger cars in the United States. It is evident that one of India's leading public health challenges also contributes meaningfully to climate change..

The coexistence of TB and diabetes mellitus (DM) (TB-DM) is associated with an increased risk of treatment failure, death, delayed culture conversion, and drug resistance. Because plasma concentrations may influence clinical outcomes, we evaluated the evidence on the pharmacokinetic (PK) of TB drugs in individuals with DM to guide management.We performed a systematic review and meta-analysis through searches of major databases from 1946 to 6 July 2023. PROSPERO (CRD42022323566).Of 4,173 potentially relevant articles, we identified 16 studies assessing rifampicin (RIF) PK, 9 on isoniazid (INH), 8 on pyrazinamide (PZA), and 3 on ethambutol (EMB). Two studies reported on second-line anti-TB drugs. According to our meta-analysis, RIF time to maximum concentration (T) was significantly prolonged in patients with DM compared with non-DM patients. We found no significant differences for RIF C, area under the curve (AUC) 0-24 or drug concentration at 2 h (C2h), INH C2h, PZA C2h, PZA T, and EMB T. Although RIF C2h was slightly reduced in patients with TB-DM, this finding was not statistically significant.This review comprehensively examines the impact of DM on the PK of TB drugs. We observed significant heterogeneity among the studies. Given the association between lower plasma concentrations and poor clinical outcomes among patients with DM, we recommend a higher dose limit to compensate for the larger body weight of patients with DM..