The WHO recommends shorter TB preventive treatment (TPT) regimens and decentralised delivery models to improve effectiveness. This study evaluated the safety of a 3-month rifampicin-isoniazid (3RH) regimen administered by community health workers (CHWs) in households in Cameroon and Uganda.A cluster-randomised trial was conducted among child contacts of TB patients. We compared the safety of 3RH delivered by CHWs at home (intervention) vs standard-of-care, facility-based administration of 3RH. Safety outcomes included adverse events (AEs), serious adverse events (SAEs), and adverse reactions (ARs). We described the steps from symptom identification by CHWs to classification by a clinician.Of 1,316 children initiated on 3RH, AEs were reported in 8.7% (81/936) in the intervention arm versus 11.3% (43/380) in the standard-of-care arm, = 0.15. Overall, 37 SAEs occurred in 36 children, all non-medication related. There were 16 ARs reported, occurring in 1.0% (9/936) of children in the intervention arm and 1.6% (6/380) in the standard-of-care arm, = 0.22. During 4,608 follow-up visits, 21 children reporting AR symptoms were identified by CHWs, 16 were assessed by clinicians, and 4 ARs were confirmed.The 3RH regimen was safe, including when administered by trained CHWs in community settings, supporting its use in decentralised healthcare models..

Low body mass index (BMI) is a globally important risk factor for TB progression. Little is known about this association in people living with HIV (PLHIV) and the functional form of the BMI-TB incidence curve.Secondary analysis of a randomised controlled trial of TB preventive therapy among PLHIV in South Africa, Mozambique, and Ethiopia. Participants received 3 months of weekly high-dose rifapentine-isoniazid given once or twice over a period of 2 years. Multivariable fractional polynomials (MFPs) were used to investigate functional forms of BMI. Time to incident TB was modelled using Cox's proportional hazard regression.A total of 76 TB events were documented, giving an overall TB incidence rate of 1.2 per 100 person-years (95%CI 1.0-1.6). Baseline BMI <18.5 kg/m² was associated with a 2.6-fold increased hazard of TB compared with BMI 18.5-24.9 kg/m² (aHR 2.6, 95% CI 1.4-4.8, < 0.001). BMI ≥30 kg/m² was associated with a lower hazard of TB (aHR 0.5, 95% CI 0.2-1.0). Continuous and categorical BMI showed weak evidence of quadratic dose-response relationships ( = 0.08 and = 0.09, respectively). MFP analysis was consistent with a decline in TB incidence for increasing BMI to around 25 kg/m², followed by a less steep decline in TB incidence for increasing BMI >25 kg/m².In PLHIV, BMI showed an inverse log-linear association with TB incidence. The MFP approach showed that the relationship is more complex than a simple log-linear association..

We describe our approach and experience with the routine implementation of stool-based Xpert MTB/RIF Ultra (Xpert) testing for the diagnosis of childhood TB in Zambia.We conducted a method validation and subsequently introduced stool as an alternative sample for routine Xpert testing for children and critically ill adults. We reviewed the impact of stool-based Xpert testing during the first 18 months of routine implementation.The method validation showed 98.0% (95% CI 92.9-99.4) agreement between Xpert results on sputum/gastric aspirate (GA) and stool specimens. During 18 months of routine implementation, 16,210 stool samples were tested, yielding 157 TB cases in children, including five rifampicin (RIF) resistant cases, and 45 cases in critically ill adults. In children aged 0-4 years, 10,288 stool samples were tested compared to 2,459 GA samples in the same period. Childhood TB notifications and the bacteriological confirmation rate increased by 30% and 53%, respectively, in 2021 compared to 2020.The routine implementation of stool testing provided access to Xpert testing for children who could not produce sputum or have GA collected, contributing to increased bacteriological confirmation of TB in children. For critically ill adults with difficulty expectorating sputum, it facilitated a rapid test result..

Mortality and causes of death in non-tuberculous mycobacterial pulmonary disease (NTM-PD) are not well-described over long follow-up periods, particularly in Europe. We investigated whether NTM-PD is associated with higher mortality rates and different causes of death than matched controls.Danish national registers were used to identify patients with NTM-PD from 2000-2017 and to match them 1:4 with controls based on age, sex, cohabitation status, and municipality.We identified 661 patients with NTM-PD (50.4% male, median age 66 years, interquartile range [IQR] 48-84). The 5-year mortality rate for NTM-PD was 51% (95% CI 47-55) compared to 15% (95% CI 14-17) for controls. The hazard ratio (HR) of death for NTM-PD was 3.1 (95% CI 2.7-3.5; < 0.001) compared to controls, persisting after adjusting for Charlson Comorbidity Index with an adjusted HR of 1.9 (95% CI 1.63-2.22; < 0.001). Median age at death was 72 years (IQR 58-86) for NTM-PD patients and 81 years (IQR 69-93) for controls. Deaths due to respiratory diseases were more frequent in NTM-PD patients (45.2%) than in controls (11.6%). Mycobacterial infection directly caused death in 5.8% of NTM-PD patients.NTM-PD is associated with significantly higher all-cause mortality than controls, particularly in the initial years following diagnosis. These findings highlight the need for increased attention to NTM-PD and related respiratory conditions..

To use molecular techniques to assess the prevalence of and in tuberculin-positive dairy cattle and to identify the risk factors for TB in these animals.A cross-sectional study was conducted from 2018 to 2020 across Mymensingh, Sirajgonj and Dhaka Districts in Bangladesh. The single intradermal comparative cervical tuberculin test was administered to 1,580 cattle suspected of having bovine TB using both avian and bovine purified protein derivative. Milk and lung tissue samples from positive animals were examined using polymerase chain reaction (PCR) to detect the causative agents of TB. Multivariable logistic regression model identified risk factors, and Sanger's dideoxy sequencing method was used for the phylogenetic analysis of PCR amplicons.Simplex PCR identified complex in 12.6% of samples. Multiplex PCR detected in 6.3% and in 3.1% of the samples. Phylogenetic analysis of 12 IS gene sequences (8 , 4 ) confirmed alignment with human isolates from Bangladesh.The study suggests potential reverse zoonotic transmission of . Further research is needed to understand the implications and assess TB transmission between humans and cattle in Bangladesh. The findings highlight the need for a comprehensive One Health approach..

Cluster randomised trials (CRTs) of TB interventions have achieved mixed results, with many lacking significant reductions in outcomes. Contamination in CRTs, resulting from short and long-term movement between clusters and the general population, may dilute the impact of measured intervention.We systematically reviewed the literature to identify CRTs that aimed to capture the population-level effects of the intervention on TB. Details of trial designs, interventions, outcomes, populations, cluster configurations, and geographic data were extracted to produce text summaries, descriptive statistics, and spatial analyses.We screened 1,039 abstracts and included 20 reports from seven CRTs. The median number of clusters was 32 (IQR 23-61), with populations ranging from 400-50,000 individuals per cluster. Four trials reported spatial data, from which the mean distance between clusters was 12.3 km (range 3.71-35.9). Several trials acknowledged design limitations, such as small cluster sizes and population mobility, which could have led to underestimations of intervention impact. Trials used various geographic, social, and pre-existing TB measures to select and allocate study clusters. Data on the potential for contamination are inconsistent.Gaps remain in the reporting of methods and results, suggesting necessary improvements to standardised reporting tools. These insights can inform recommendations for improved CRT design and reporting practices..

To assess the predictive value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, and systemic immune inflammation index in severe post-operative pulmonary infection in haemorrhagic stroke patients based on sex.This retrospective study included 193 male and 129 female patients with haemorrhagic stroke and post-operative pulmonary infection. Univariate and multivariate logistic regression models were used to determine the association between inflammatory markers from peripheral blood counts and severe pulmonary infection in these patients.The proportions of severe pulmonary infections in male and female patients were respectively 35.8% and 24.8%, with a significant difference. Among female haemorrhagic stroke patients, the results of the multivariate logistic regression model showed that the NLR on the third post-operative day (≥9.17) was associated with severe pulmonary infection. Among male haemorrhagic stroke patients, the results of the multivariate logistic regression model showed that NLR on the first post-operative day (≥13.28) and NLR on the third post-operative day (≥8.85) were associated with severe pulmonary infection.The predictive values of NLR for post-operative severe pulmonary infection varied among haemorrhagic stroke patients of different sexes. However, a higher NLR on the third post-operative day was associated with severe pulmonary infection in both male and female patients with haemorrhagic stroke..

Although physical activity is an important outcome in patients with chronic respiratory disease, it has not been characterised in those with non-tuberculous mycobacterial pulmonary disease (NTM-PD). This study aimed to evaluate physical activity and its associated factors in patients with NTM-PD.This prospective observational study measured daily step counts using an accelerometer to assess physical activity (steps per day). We investigated serum C-reactive protein (CRP), incremental shuttle walk test distance (ISWD), Leicester Cough Questionnaire (LCQ), modified Medical Research Council (mMRC) dyspnoea scale, and chronic cough and sputum symptoms (CCS). Patients were divided into two groups based on the presence or absence of CCS, and their physical activity were compared. The association between physical activity and these variables was examined using multivariate analysis.We included 131 patients, with a median daily step count of 3,960. Patients with CCS had significantly lower daily step counts than those without CCS (3,426 vs 4,567). Daily step count significantly correlated with age, mMRC dyspnoea grade, CRP level, ISWD, and LCQ. Multiple regression analysis showed that the daily step count was significantly associated with ISWD and CCS.These results suggest that CCS should be considered when assessing physical activity in patients with NTM-PD..

Population-based surveys are crucial for understanding smoking and TB epidemiology.A sub-national cross-sectional survey was conducted among individuals aged ≥15 years in 180 clusters in Southern India.Among 130,914 participants included for analysis, 117,091 were non-smokers, 5,410 were past smokers, and 8,413 were current smokers. Sixty-two (0.7%) participants in the current smoking group, 31 (0.6%) participants in the past smoking group, and 151 (0.1%) participants in the non-smoking group were diagnosed with microbiologically confirmed pulmonary TB (MCPTB). The crude prevalence ratio (cPR) of MCPTB in the smoking population was 4.33 (95% CI 3.30-5.68, < 0.01). The adjusted PR (aPR) of MCPTB among the smoking population for the 31-45-years age group was 4.38 (95% CI 0.96-20.04); among those aged 46-60 years, this was 9.69 (95% CI 2.29-40.91); and among those aged >60 years, it was 11.59 (95% CI 2.74-49.05). The aPR among those with a body mass index of <16.50 kg/m², was 13.18 (95% CI 5.46-31.86). The aPR among those with alcohol use was 2.43 (95% CI 1.10-5.35), and 3.19 (95% CI 1.79-5.69) among those with a history of TB.The prevalence of MCPTB in smokers is significantly higher than in non-smokers. Increasing age, undernutrition, alcohol use, and history of PTB were strongly associated with PTB among smoking participants..

Existing TB diagnostic tests rely on sputum samples, which can be difficult to collect from all patients. This study examines plasma cell-free DNA (Mtb cfDNA) based quantitative PCR (qPCR) assay for the diagnosis of pulmonary TB (PTB).The qPCR assay targeted insertion sequence (IS), and R genes on plasma samples from 106 PTB patients and 60 controls. Sensitivity was calculated using the Xpert MTB/RIF test, culture, and clinical diagnosis for the PTB group, while specificity was determined based on results from controls.Among PTB cases, 92 (86.8%) were bacteriologically confirmed, with the remaining 14 (13.2%) diagnosed clinically. The sensitivity of the plasma Mtb cfDNA assay, considering all three genes, was 71.7% (95% CI 62.6-71.7) for all PTB cases, with higher sensitivity in bacteriologically confirmed cases (78.3%) than in clinically diagnosed cases (28.6%). The combined specificity was 91.7%. The combination of IS and targeted qPCR demonstrated a sensitivity of 70.8%, and IS and R showed a sensitivity of 69.8%. However, R and resulted in a lower sensitivity of 63.2%. IS and had sensitivities of respectively 59.4% and 60.4%, while R had 53.8%.Targeting multiple genes for plasma Mtb cfDNA-based TB diagnosis improves sensitivity and could be an important addition to current sputum-based diagnostic approaches..

Sputum culture is the gold standard for diagnosing TB disease and confirming treatment outcomes. However, the turnaround time is 6-8 weeks, which leads to delays in decision-making regarding the care of TB patients.To evaluate isoniazid hair drug levels as a predictor of sputum culture conversion at 8 weeks of TB treatment.We enrolled 56 TB patients and started them on treatment. We collected sputum and hair samples at baseline and Weeks 4, 8, and 26. Sputum culture was done on solid and liquid media. The hair drug levels assay was done using liquid chromatography-tandem mass spectrometry.We excluded 22 participants (8 with contaminated cultures, 10 were unable to produce sputum, and 4 missed the Week 8 visit). Of the remaining 28, about 24 (86%) were TB sputum culture-negative with a median hair drug level of 0.0514 ng/ml (IQR 0.1165-0.0314), and 4 (14.1%) were TB culture-positive, with a median hair drug level of 0.0192 (IQR 0.0267-0.0132).A median isoniazid hair level of ≥0.05 ng/ml may be predictive of sputum culture conversion by the end of the intensive phase of TB treatment..

In recent years, research on TB multimorbidity has increasingly focused on integrated care delivery, particularly concerning common mental disorders (CMDs). Engagement with relevant stakeholders, including service users and providers, has highlighted the critical intersection of TB and CMD, which affects a substantial percentage of individuals. Studies have found that depression affects approximately 45% of TB patients, and anxiety affects around 40%. Moreover, there is a significant evidence and service gap in delivering CMD care, which emphasises the need for a comprehensive approach to address the dual burden of these health challenges.