Post-tuberculosis lung disease

There is a high burden of both diabetes (DM) and tuberculosis (TB) in China, and as DM increases the risk of TB and adversely affects TB treatment outcomes, there is a need for bidirectional screening of the two diseases. How this is best performed is not well determined. In this pilot project in China, we aimed to assess the feasibility and results of screening DM patients for TB within the routine healthcare setting of five DM clinics. Agreement on how to screen, monitor and record was reached in May 2011 at a national stakeholders meeting, and training was carried out for staff in the five clinics in July 2011. Implementation started in September 2011, and we report on 7 months of activities up to 31 March 2012. DM patients were screened for TB at each clinic attendance using a symptom-based enquiry, and those positive to any symptom were referred for TB investigations. In the three quarters, 72% of 3174 patients, 79% of 7196 patients and 68% of 4972 patients were recorded as having been screened for TB, resulting in 7 patients found who were already known to have TB, 92 with a positive TB symptom screen and 48 of these newly diagnosed with TB as a result of referral and investigation. All patients except one were started on anti-TB treatment. TB case notification rates in screened DM patients were several times higher than those of the general population, were highest for the five sites combined in the final quarter (774/100 000) and were highest in one of the five clinics in the final quarter (804/100 000) where there was intensive in-house training, special assignment of staff for screening and colocation of services. This pilot project shows that it is feasible to carry out screening of DM patients for TB resulting in high detection rates of TB. This has major public health and patient-related implications.

SummaryBackgroundExisting Tuberculosis (TB) elimination strategies show limited impact, with suboptimal uptake of tuberculosis preventive treatment (TPT) and increasing TB incidence after the COVID-19 pandemic. Real-world evidence on reduction of tuberculosis in high-burden communities is needed to inform future TB elimination strategies.MethodsSince 2017, a comprehensive TB screening and TPT program known as Zero TB in Kids (ZTBK) was implemented in congregate settings of Tibetan communities in India. TB disease, TB infection (TBI), tuberculin skin test (TST) conversion, and TPT uptake were measured periodically.FindingsSchoolchildren and adults in 63 institutes (n = 20,068; 67,637 person-years) were screened. TPT was given to 3847 participants. TB incidence decreased 83% between 2017 [576 (95% CI: 455–718)/100,000] and 2024 [97 (47–179)/100,000]. TB infection (TBI) prevalence decreased 32% between 2017 [22% (95% CI: 21–23%)] and 2024 [15.5% (14–17%)]. TB incidence (640/100,000) and TBI prevalence (28%) were higher in the institutes that were never screened before under ZTBK. Among participants who did not receive TPT, TB disease prevalence decreased 84% between 2017 [910 (95% CI: 675–1204)/100,000] and 2024 [147 (48–343)/100,000], indicating a herd benefit. After one round of TB screening and TPT, between 2018 and 2019, TST conversion decreased 59% for children and 47% for adolescents. Risk of TBI was greater for males (aPR: 1.23; 95% CI: 1.16–1.30). TB risk was 82% lower for schoolchildren receiving TPT. Participants with seizure disorder [aPR: 0.31 (95% CI: 0.15–0.65)] and hepatitis B [0.71 (0.6–0.84)] were less likely to receive TPT.InterpretationSignificant reduction of TB transmission and burden can be achieved using the existing tools of TB control. Surveillance of TBI and TPT must be widely adopted for schools and congregate settings with high TB burden.Funding10.13039/100000002National Institutes of Health-10.13039/100000060National Institute of Allergy and Infectious Diseases (NIAID) (K01-AI148583), STOP TB Partnership (STBP/TBREACH/GSA/W7-7692), NIAID-Johns Hopkins Center for AIDS Research (90100777), Foundations, and Philanthropy.

The steadily growing epidemic of diabetes mellitus poses a threat for global tuberculosis (TB) control. Previous studies have identified an important association between diabetes mellitus and TB. However, these studies have limitations: very few were carried out in low-income countries, with none in Africa, raising uncertainty about the strength of the diabetes mellitus-TB association in these settings, and many critical questions remain unanswered. An expert meeting was held in November 2009 to discuss where there was sufficient evidence to make firm recommendations about joint management of both diseases, to address research gaps and to develop a research agenda. Ten key research questions were identified, of which 4 were selected as high priority: (i) whether, when and how to screen for TB in patients with diabetes mellitus and vice versa; (ii) the impact of diabetes mellitus and non-diabetes mellitus hyperglycaemia on TB treatment outcomes and deaths, and the development of strategies to improve outcomes; (iii) implementation and evaluation of the tuberculosis 'DOTS' model for diabetes mellitus management; and (iv) the development and evaluation of better point-of-care diagnostic and monitoring tests, including measurements of blood glucose and glycated haemoglobin A(1c) (HbA(1c)) for patients with diabetes mellitus. Implementation of this research agenda will benefit the control of both diseases.

To investigate whether an unrecognised diagnosis of tuberculosis (TB) at the start of antiretroviral therapy (ART) influences subsequent CD4+ T cell (CD4) count recovery in an urban HIV clinic in Uganda. In a retrospective cohort study, a multivariable polynomial mixed effects model was used to estimate CD4 recovery in the first 96 weeks of ART in two groups of patients: prevalent TB (started ART while on TB treatment), unrecognised TB (developed TB within 6 months after start ART). Included were 511 patients with a median baseline CD4 count of 57 cells/mm(3) (interquartile range: 22-130), of whom 368 (72%) had prevalent TB and 143 (28%) had unrecognised TB. Compared with prevalent TB, unrecognised TB was associated with lower CD4 count recovery at 96 weeks: -22.3 cells/mm(3) (95% confidence interval -43.2 to -1.5, P = 0.036). These estimates were adjusted for gender, age, baseline CD4 count and the use of zidovudine-based regimen. Unrecognised TB at the time of ART initiation resulted in impaired CD4 recovery compared with TB treated before ART initiation. More vigilant screening with more sensitive and rapid TB diagnostics prior to ART initiation is needed to decrease the risk of ART-associated TB and sub-optimal immune reconstitution.

Systematic screening of household contacts (HHCs) of people with tuberculosis (TB) and starting them on either TB treatment or tuberculosis preventive treatment (TPT) reduces TB incidence. This project supported HHC management in six health facilities in Zimbabwe through the provision of CXR services, reimbursement of transport costs for HHCs, and provision of fuel and refreshments for healthcare workers involved in contact tracing. We describe TB and TPT cascades among the HHCs of index patients with all forms of TB. We enrolled 251 index patients who listed 794 HHCs: 551 (69%) HHCs of 158 index patients were traced and 520 (94%) screened for TB. Of the 502 who were referred to clinics, 362 (72%) reached the clinic. Among 520 HHCs, 324 (62%) underwent CXR screening and 18 (5%) had CXRs suggestive of TB. The yield of TB was 2.3% (12/520), with CXR detecting eight people who had not reported TB symptoms. Of the 311 who were assessed for TPT eligibility, 126 (41%) started TPT and 119 were assessed for TPT outcomes. Of these, 111 (93%) had successful TPT outcomes. The median times to starting TB treatment and TPT were 7 days and 11 days, respectively. The intervention facilitated timely access to healthcare services and a high yield of TB detection.

To help achieve the End TB Strategy target of a 90% reduction in tuberculosis (TB) incidence by 2030, member states of the United Nations High-Level Meetings on TB called for improving provision of TB preventive treatment (TPT) for household contacts of persons with TB, who are at increased risk for infection and disease. However, TPT use among household contacts worldwide remained at 21% in 2023. The International Union Against Tuberculosis and Lung Disease, the Uganda Ministry of Health, and CDC piloted a comprehensive approach for increasing case finding and TPT coverage among household contacts of persons with TB. During November 1, 2023-September 30, 2024, a total of 521 index patients with TB disease were registered at six health facilities in Uganda. Home visits to index patients identified 1,913 household contacts, 1,739 (91.0%) of whom underwent TB symptom screening at home; 321 (18.5%) reported TB symptoms. Of 309 (96.3%) persons with TB symptoms who were further evaluated, 284 (91.9%) provided a sputum specimen for laboratory testing, including 270 (84.1% of those with symptoms) who did so during the home visit; 214 (69.3%) underwent chest radiography. Overall, 80 TB cases were diagnosed; in 61 (76.3%) persons, the diagnosis was based on radiographic findings. Among 1,496 HHCs eligible for TPT, 1,239 (82.8%) initiated treatment and 1,178 (95.1%) completed it. Global scale-up of this approach might help reach global TB elimination goals.

“Won’t Get Fooled Again” (by Tuberculosis)

Mycobacterium tuberculosis Infections in Solid Organ Transplantation

IntroductionThe WHO estimates a gap of about 30% between the incident (10.6 million) and notified (7.5 million) cases of tuberculosis (TB). Combined with the growing recognition in prevalence surveys of...

Background: the effect of pulmonary rehabilitation (PR) services, beyond research contexts, on patients with lung diseases other than COPD requires further study. Objectives: to (i) assess the impact of a publicly funded PR on patients’ exercise capacity, self-efficacy, and health-related quality of life (HRQoL), and (ii) explore whether the effects vary across lung diseases. Methods: this retrospective pre–post study analyzed data from the Winnipeg Regional Health Authority PR program between 2016 and 2019. Results: 682 patients completed the full PR program. Pooled analyses found significant improvements in the patients’ exercise capacity (six-minute walk test (6MWT) (13.6%), fatigue (10.3%), and dyspnea (6.4%)), Self-Efficacy for Managing Chronic Disease 6-Item Scale (SEMCD6) (11.6%), and HRQoL (Clinical COPD Questionnaire (CCQ) (18.5%) and St George’s Respiratory Questionnaire (SGRQ) (10.9%)). The analyses conducted on sub-groups of patients with chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis, interstitial lung diseases (ILDs), other restrictive lung diseases (e.g., obesity, pleural effusion, etc.), lung cancer, and pulmonary hypertension (PH) indicated that, except for patients with PH, all the patients improved in the 6MWT. Fatigue decreased in patients with COPD, ILDs, and other restrictive lung diseases. Dyspnea decreased in patients with COPD, asthma, and lung cancer. SEMCD6 scores increased in COPD, ILDs and PH patients. CCQ scores decreased in all lung diseases, except lung cancer and PH. SGRQ scores only decreased in patients with COPD. Conclusion: PR services had a significant impact on patients with different lung diseases. Therefore, publicly funded PR should be available as a critical component in the management of patients with these diseases.

Three months of isoniazid-rifapentine (3HP) is being scaled up for tuberculosis (TB) preventive treatment (TPT) among people living with HIV (PLHIV) in high-burden settings. More evidence is needed to identify factors influencing successful 3HP delivery. We conducted a qualitative assessment of 3HP delivery nested within the 3HP Options Trial, which compared three optimized strategies for delivering 3HP: facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), and patient choice between facilitated DOT and facilitated SAT at the Mulago HIV/AIDS clinic in Kampala, Uganda. We conducted 72 in-depth interviews among PLHIV purposively selected to investigate factors influencing 3HP acceptance and completion. We conducted ten key informant interviews with healthcare providers (HCPs) involved in 3HP delivery to identify facilitators and barriers at the clinic level. We used post-trial 3HP delivery data to assess sustainability. We used thematic analysis (inductive and deductive) to align the emergent themes with the RE-AIM framework dimensions to report implementation outcomes. Understanding the need for TPT, once-weekly dosing, shorter duration, and perceived 3HP safety enhanced acceptance overall. Treatment monitoring by HCPs and reduced risk of HIV status disclosure enabled DOT acceptance. Dosing autonomy enabled SAT acceptance. Switching between DOT and SAT as needed enabled acceptance of patient choice. Dosing reminders, reimbursement for clinical visits, and social support enabled 3HP completion; pill burden, side effects, and COVID-19-related treatment restrictions hindered completion. All HCPs were trained and participated in 3HP delivery with high fidelity. Training, care integration, prior TPT experience with daily isoniazid, and few 3HP-related serious adverse events enabled adoption, whereas initial concerns about 3HP safety among HCPs, and COVID-19 treatment disruptions delayed 3HP adoption. Refresher training and collaboration among HCPs enabled implementation whereas limited diagnostic facilities for adverse events at the clinic hindered implementation. SAT was modified post-trial; DOT was discontinued due to inadequate ongoing financial support beyond the study period. Facilitated delivery strategies made 3HP treatment convenient for PLHIV and were feasible and implemented with high fidelity by HCPs. However, the costs of 3HP facilitation may limit wider scale-up. Trial registration: ClinicalTrials.gov (NCT03934931); Registered 2nd May 2019; https://clinicaltrials.gov/study/NCT03934931?id = NCT03934931&rank = 1.

Despite WHO's recommendations and the 2023-2030 Tuberculosis (TB) action plan, uptake of TB preventive treatment (TPT) remains suboptimal. In this paper, we use two countries of the WHO Europe Region, the Republic of Moldova and Georgia, that are at different stages of implementation of TB prevention policies, as a case study to examine health system barriers and facilitators to TPT scale-up. In this case study, we used methods of qualitative research-interviews with three stakeholder groups: health service providers and National TB Programme staff; civil society organisations and international partners or donors. The data were collected via videoconference, transcribed, then coded and analysed using NVivo V.14. Thematic analysis was conducted. Facilitators for TPT delivery in both settings include an established TB clinical network, well-functioning communication systems and an uninterrupted supply of TPT medicines.In both settings, healthcare providers generally exhibit positive attitudes towards treating TB infection; however, some remain sceptical and cautious, particularly regarding prescribing TPT without confirmation of TB infection, a challenge compounded by limited access to testing for TB infection. Evidence of TB infection is also important for patients' decisions on initiation and adherence to treatment. Other barriers to effective service delivery of TPT include shortages and high workload of primary healthcare personnel, ambiguity in the role of family doctors in the management of TPT and low prioritisation of TPT during regular monitoring visits. The case study identified similar challenges in the rollout of TPT across both settings, highlighting common barriers hindering effective implementation. For optimal TPT rollout, enhancing provider confidence, improving access to testing for TB infection and strengthening integration with primary healthcare with refined roles of family doctors are essential. Both settings would also benefit from improved monitoring and evaluation systems and prioritisation of TB prevention in monitoring.

BackgroundVarious factors influence tuberculosis preventive treatment (TPT) decisions thus it is important to understand the health beliefs and concerns of patients before starting TPT to ensure treatment compliance. This study aims to explore facilitators and barriers for TPT among patients diagnosed with Latent Tuberculosis infection (LTBI) attending six primary healthcare clinics in Selangor, Malaysia.MethodIn-depth interviews were conducted face-to-face or via telephone among patients with a clinical diagnosis of LTBI using a semi-structured topic guide developed based on the common-sense model of self-regulation and literature review. Audio recordings of interviews were transcribed verbatim and analysed thematically.ResultsWe conducted 26 In-depth interviews; Good knowledge of active tuberculosis (TB) and its associated complications, including the perceived seriousness and transmissibility of active TB, facilitates treatment. LTBI is viewed as a concern when immune status is compromised, thus fostering TPT. However, optimal health is a barrier for TPT. Owing to the lack of knowledge, patients rely on healthcare practitioners (HCPs) to determine their treatment paths. HCPs possessing comprehensive knowledge play a role in facilitating TPT whereas barriers to TPT encompass misinterpretation of tuberculin skin test (TST), inadequate explanation of TST, and apprehensions about potential medication side effects.ConclusionsKnowledge of LTBI can influence TPT uptake and patients often entrust their HCPs for treatment decisions. Improving knowledge of LTBI both among patients and HCPs can lead to more effective doctor-patient consultation and consequently boost the acceptance of TPT. Quality assurance should be enhanced to ensure the effective usage of TST as a screening tool.

Background:Tuberculosis (TB) affects patients' quality of life due to symptoms and social stigma, especially in low-income settings like Ghana. However, data on factors influencing health-related quality of life (HRQOL) in such environments are limited. Identifying these factors is essential for improving treatment outcomes through holistic care.Objective:This study determined the impact of sociodemographic and clinical factors on HRQOL at treatment initiation, and monitored changes until the end of treatment.Design:Prospective observational study.Methods:A cohort of 378 newly diagnosed patients with drug-susceptible TB (mean age: 45.3 ± 15.1 years) was followed across eight hospitals in the Ashanti and Eastern regions of Ghana. Patients received first-line antitubercular treatment, and HRQOL was assessed at baseline, month 2, and month 6 using an interviewer-administered SF-12v2 questionnaire. Associations between HRQOL and sociodemographic or clinical factors were examined using Chi-square or Fisher’s exact tests, while logistic regression was used to estimate crude and adjusted odds ratios (p < 0.05).Results:At baseline, 78.8% of participants had impaired physical HRQOL, and 25.7% were at risk of depression. At treatment completion, physical HRQOL impairment remained high (59.5%), with 15.0% still at risk of depression. Only 44.7% showed clinically significant improvement in physical HRQOL, while 39.8% improved in mental HRQOL. Employment, HIV-positive status, and alcohol use were associated with poorer mental HRQOL. Extrapulmonary TB patients demonstrated better physical HRQOL at both the beginning and end of treatment but exhibited poorer mental HRQOL at treatment completion. Widowed participants improved mentally despite poorer baseline health, while married individuals had better physical HRQOL. Higher education correlated with better baseline mental health but lower odds of significant HRQOL improvement.Conclusion:Sociodemographic and clinical factors significantly influenced HRQOL in drug-susceptible TB patients after 6 months of treatment. These findings underscore the importance of targeted mental health support during and after treatment to improve patient well-being.

Tuberculosis preventive treatment (TPT) is a mainstay for reducing the tuberculosis (TB) burden among people living with human immunodeficiency virus (PLHIV). Context-specific challenges hinder TPT uptake and completion among PLHIV. During 2022–2024, a mixed-methods design was used to evaluate the TPT cascade and explore its facilitators and barriers among PLHIV availing care from 12 PEPFAR-supported health facilities in Uganda. The quantitative component included analysis of routine programmatic data, and the qualitative component included focus group discussions and in-depth interviews with healthcare workers and PLHIV. A total of 1349 PLHIV were enrolled in the evaluation. Among PLHIV newly initiated on ART (≤3 months), 74% started TPT, and 98% of them completed it. In PLHIV already on ART, 87% had initiated TPT (76% before and 11% during this evaluation), with a treatment completion rate of 98%. The facilitators for TPT implementation included access to shorter TPT regimens, integration of services, and adherence counseling. Barriers included knowledge gaps, pill burden, TPT drug stock-outs, and documentation inconsistencies. The TPT completion rate was higher than the national target (90%), but the TPT initiation remains low. Improved access to shorter regimens, adherence counseling, better documentation, and service integration can sustain the completion rate and improve the initiation rate in Uganda and possibly elsewhere.