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Post-TB health and wellbeing
Abstract
TB affects around 10.6 million people each year and there are now around 155 million TB survivors. TB and its treatments can lead to permanently impaired health and wellbeing. In 2019, representatives of TB affected communities attending the '1st International Post-Tuberculosis Symposium´ called for the development of clinical guidance on these issues. This clinical statement on post-TB health and wellbeing responds to this call and builds on the work of the symposium, which brought together TB survivors, healthcare professionals and researchers. Our document offers expert opinion and, where possible, evidence-based guidance to aid clinicians in the diagnosis and management of post-TB conditions and research in this field. It covers all aspects of post-TB, including economic, social and psychological wellbeing, post TB lung disease (PTLD), cardiovascular and pericardial disease, neurological disability, effects in adolescents and children, and future research needs.
... On average, 47.3% of individuals diagnosed with TB lose out on work productivity while they are recovering [4]. The above may have an economic impact on communities to the extent that up to a third of individuals who complete TB treatment are still unemployed [5]. Some of the common symptoms related to TB that influence an individual diagnosed with TB's ability to return to work are low physical endurance, loss of motivation, and a loss of self-esteem [6]. ...
... Other psychosocial factors include the stigma that society has towards individuals with TB due to the fear of becoming infected by them [7]. The worker roles of individuals diagnosed with TB are affected, as they often struggle to complete work tasks due to their symptoms of low physical endurance [5]. It could be argued that due to the unemployment rate, individuals with TB could experience stigma in the workplace as they may not be accommodated in the workplace. ...
... It could be argued that due to the unemployment rate, individuals with TB could experience stigma in the workplace as they may not be accommodated in the workplace. This may result in these individuals experiencing low self-esteem and negatively affecting their ability to hold jobs when becoming reinfected [5]. Many of these individuals may have low self-esteem and could struggle to maintain work when they get reinfected. ...
Background: Individuals diagnosed with tuberculosis (TB) and multidrug-resistant (MDR) TB may struggle to return to work after they have completed a rehabilitation program. Multidrug-resistant tuberculosis (MDRTB) has been seen as a condition that is resistant to treatment, hence causing individuals to be economically in-active for considerable periods of time.
Objective: The aim of the current study was to explore the views of individuals living with MDRTB, individuals with TB, and health professionals treating individuals with TB and MDRTB about the development of a vocational rehabilitation program.
Method: The researchers used an exploratory descriptive research design, and semistructured interviews were conducted with five key informants and four participants who were diagnosed with pulmonary tuberculosis (PTB) and MDRTB. Thematic analysis was used in order to analyse the study findings. The current study is the second of two articles. The first article focused on barriers and facilitators linked to returning to work for individuals living with TB and MDRTB. The current article focuses on the development of a vocational rehabilitation program.
Results: The findings of the original study revealed five themes; however, for the purpose of this article, only two themes will be presented, namely, Theme 1: promoting a holistic model and Theme 2: the use of resources for activity engagement. The latter theme contributed to the participant’s view of the development of a vocational rehabilitation program.
Conclusion: The study provided a description of the components of a vocational rehabilitation program that has been adapted from the Model of Occupational Self-Efficacy (MOOSE). The above program has been designed for individuals diagnosed with PTB/MDRTB and has the potential to assist them in returning to work. It is suggested that vocational rehabilitation programs be incorporated into general medical programs that focus on improving the functioning of individuals diagnosed with PTB/MDRTB.
... 19 Aproximadamente un tercio de los pacientes que sobreviven a la tuberculosis pulmonar enfrentan, una vez finalizado el tratamiento, una carga considerable -y a menudo poco reconocida-de morbilidad continua, que incluye insuficiencia respiratoria, infecciones de repetición, desafíos psicosociales y una reducción de la calidad de vida relacionada con la salud. 3,4 Incluso, la mortalidad es mayor en los pacientes con PTLD: los estudios indican un riesgo de muerte hasta 6 veces mayor que en la población general. 5,6 A pesar del reciente aumento en el número de publicaciones relacionadas con la PTLD, aún no se conoce bien la carga epidemiológica real ocasionada por la PTLD 12 y la morbilidad asociada. ...
... La evaluación y el tratamiento temprano y oportuno de la morbilidad relacionada con la PTLD, guiados por las recomendaciones sólidas de una sociedad científica, son de suma importancia para garantizar la adecuada asignación de recursos a los servicios de tuberculosis, así como también para promover y fomentar diversas actividades de prevención, diagnóstico y tratamiento de la calidad de vida relacionada con la salud. 3,4 Por todo lo expuesto, el Departamento de Tuberculosis de ALAT ha decidido publicar este documento, donde se definen y enumeran criterios y recomendaciones de acción para el tratamiento de los pacientes con PTLD de nuestra región. ...
... Conociendo que muchos servicios de la región no cuentan con todas las pruebas antes mencionadas, se establece que las recomendaciones se deben adaptar a los recursos disponibles, siempre incluyendo el mínimo de evaluación clínica: radiografía de tórax, espirometría, oximetría de pulso y puntuación de síntomas, y cuestionario de calidad de vida. 1,4,10,12,22,[26][27][28][29][30][31][32] Parámetros para evaluar 1 Historia clínica: anamnesis y examen físico Los patrones clínicos de la PTLD incluyen un amplio espectro de signos y síntomas que varían desde pacientes asintomáticos hasta la discapacidad respiratoria grave. Algunos de los síntomas que motivan habitualmente las consultas son tos crónica y disnea, 33 muchas veces acom-pañadas de hemoptisis. ...
AbstractIntroduction: Efforts to combat tuberculosis (TB) usually focus on early, rapid diagnosis and effective treatment to break the chain of transmission of Mycobacterium tubercu-losis. However, in the last few years, coinciding with the syndemic TB/COVID-19 asso-ciation, more and more evidence has proved the serious clinical, functional and psycho-social sequelae that TB can cause. This condition has been defined as Post-Pulmonary Disease Tuberculosis (PTLD) and it affects approximately one-third of the patients who survive TB, facing persistent respiratory symptoms with episodic exacerbations, chro-nic respiratory failure, emotional disorders and psychosocial challenges that negatively impact their life quality, meaning a high catastrophic cost.Objective: Provide a shared, guiding and scientifically valid model to promptly diagno-se, evaluate and treat patients with PTLD (prevention, diagnosis, treatment and possi-ble rehabilitation).Methodology: It is documentary research that includes systematic reviews, meta-analysis, observational studies and the guidelines that have existed in recent years in this regard, added to an evaluation by experts, with the purpose of adapting them to lo-cal conditions of each Latin American country.Conclusions: Considering the global and, particularly, the Latin American burden of TB, and the estimated burden of PTLD, the development of a consensus document on this topic is urgent. Therefore, we think ALAT recommendations will provide the basis for the formulation and adoption of national specific guidelines for the management of PTLD in Latin America.
... The long-term effects of PTLD in children are related to school performance, child development, physical growth, stigma and discrimination, and the prevalence of depression and anxiety after TB therapy. Also, these long-term effects are more extensive compared to adults due to the continued lung development into young adulthood and lower respiratory tract infections at a young age can affect future lung function [5]. Airway abnormalities may include airway obstruction diagnosed through spirometry and bronchiectasis diagnosed through chest imaging or CT scans [4,6]. ...
... However, supportive management such as pulmonary rehabilitation can be provided and every patient who has completed TB treatment should be clinically evaluated for post-TB lung disease. In cases of limited facilities, priority should be given to history taking, symptom assessment, physical examination, chest Xray, spirometry, pulse oximetry, 6-minute walk test, symptom scoring, and quality of life questionnaires [5,9,10]. ...
... Structural and functional pulmonary sequelae of varying degrees of severity are issues encountered in post-TB lung disease [10]. Ideally, spirometry should be performed serially at several points: at the initial TB diagnosis, at the end of treatment, and during follow-up in severe TB cases [5,12]. Some studies have shown improvement in spirometry results among TB survivors during follow-up [13][14][15][16]. ...
Background Tuberculosis (TB) remains a significant issue due to its high incidence and mortality rates but there is a lack of studies addressing the conditions that may arise after treatment, particularly lung impairment in children. Therefore, this study assessed the lung function of adolescents who had undergone TB treatment. Methods This comparative, analytical, non-experimental study with a cross-sectional design was conducted using secondary data from a previous study involving fifty-two participants with drug-sensitive TB (DS-TB) and drug-resistant TB (DR-TB) treated at Hasan Sadikin General Hospital, Bandung, Indonesia, from July to September 2024. Chest high-resolution computed tomography (HRCT) scans were performed using the Hitachi Sceneria CT-Scanner® and spirometry was conducted with the MIR Spirolab® device utilising a forced expiratory manoeuvre to analyse changes in forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). Data analysis was conducted using paired t-tests in IBM SPSS with a significance level of p < 0.05 and a 95% confidence interval. Results Of the fifty-two adolescent pulmonary TB survivors contacted, two of them died and 27 participants were excluded because they were not contactable. HRCT scans of the remaining 23 adolescents identified primarily fibrosis, nodules, and ground-glass appearance (20/23, 19/23, and 10/23, respectively). Only 2 participants had normal HRCT findings and both were DS-TB survivors. Comparative spirometry results over the one-year (mean 12.7 months) follow-up showed a significant increase in FEV1 (p = 0.033, 95% confidence interval [0.5–11.4]) and FVC (p = 0.008, 95% confidence interval [2.1–12.8]). Conclusions HRCT scans are essential in the follow-up of adolescent TB survivors as they provide insights into lung damage and detect complications. Repeated spirometry is also necessary to assess and monitor lung function in TB survivors.
... Post-TB lung disease (PTLD) is an increasingly recognized complication of tuberculosis, [2][3][4][5] The First International Post-Tuberculosis Symposium (2019) established the minimum case definition for PTLD as "evidence of chronic respiratory abnormality, with or without symptoms, attributable at least in part to previous tuberculosis" [6]. ...
... In 2023 Nightingale et al. advocated that the management of post-TB care should extend beyond PR and recommended medical management based on various clinical phenotypes of PTLD. However, they acknowledge that PTLD-specific data is lacking and therefore treatment for these phenotypes must currently be extrapolated from other contexts, representing an additional key knowledge gap [3]. ...
... International guidelines and national policies provide little guidance on treatment of PTLD. Current clinical standards provide recommendations for pulmonary rehabilitation [4] and limited recommendations on pharmacologic therapy [3]. Recommendations on treating chronic hypoxemia and pulmonary hypertension are lacking. ...
The burden of long-term functional impairment following curative treatment for tuberculosis (TB) constitutes a significant global health problem. By some estimates, chronic respiratory impairment, or post-tuberculosis lung disease (PTLD), is present in just over half of all patients who have completed TB therapy. Despite this high prevalence and substantial associated morbidity, discussion of PTLD is essentially absent from international and national TB policies and guidelines. Clear and ambitious clinical standards should be established for the diagnosis and management of PTLD, including the stipulation that all patients completing TB therapy should be screened for PTLD. Patients diagnosed with PTLD should receive linkage to chronic care, with access to inhalers and home oxygen, as indicated based on individual symptoms and pathophysiology. Leveraging their considerable influence, major funders, such as The Global Fund, could help close the gap in PTLD care by including PTLD in their strategic vision and funding streams. Immediate action is needed to address the substantial burden of disease associated with PTLD. This will require expanding the global approach to TB to include a commitment to diagnosing and treating long-term complications following initial curative therapy.
... The standard quality of care/service may include, among other conditions, the type of drugs/medicines prescribed and then used to result into certain treatment outcome(s), and this sometimes depends also on the nature of the process involved in delivering the care received/accessed by the client/patient (37). Part of the process care-that is, the procedure concerned relates to the time spent by the client to wait for service at the clinic/ facility, the service providers' attitude including the language such providers use while interacting with their patients, in addition to the physical environment in which the services are being delivered (38,39). ...
... Patients and survivors tend to expect social support from other people with whom they interact (55)(56)(57). Therefore, there is a need to make social support a part of the policies that are created and established programs, to strengthen efforts towards ending TB (38,53,54). Findings indicated that there is more to be done with regard to TB treatment than just administering drugs (58). ...
... Some of the individuals who face post-TB lung disease endure lifelong sequelae (65). This condition may traumatize them for many years, especially, in times that they encounter people who mistreat them (38) The feedback received from both categories of participants confirmed that TB is a burdensome disease not only during the moments of physical health deterioration but also after undergoing treatment and getting cured of the disease (38). Therefore, the current study's findings validate the earlier reported evidence justifying the need for a renewed interest and focus on TB's burden and damaging impact, particularly its long-term sequelae on individual patients, their households, and their communities (67). ...
Introduction
Pulmonary tuberculosis (PTB) remains a life-threatening disease in Tanzania, with negative physical, financial, economic and psychosocial consequences to individuals and the society. It mainly lowers the quality of life of patients, survivors and their families, especially those in the poorest and socially deprived categories.
Objectives
To report and discuss a qualitative study that assessed the nature of social support desired and received by PTB patients and survivors. Participants were given a chance to share their experiences and their perceptions on whether the social support they desired had an impact on their treatment-seeking behaviour and treatment adherence.
Methods
Face-to-face interviews were conducted with the three aforementioned groups, purposively selected at a TB clinic between October 2020 and March 2021. The questions covered topics related to the types of social support desired and the sources of support during and after treatment, if any. Interviews were concluded until no new information was obtained. Data analysis was facilitated using NVivo 12 software.
Results
Participants pointed out a need for psychosocial, financial, and material support during and after treatment. However, they sometimes miss support from family/household members or the rest of the community. Because of this experience, they lived with difficulties, facing hardships when required to pay out of pocket for transport during the care-seeking. Survivors testified experience of a denial of support by even their close relatives who regarded them as no longer needing it after recovering. Patients and survivors also reported experience of social isolation as they were believed able to transmit PTB infections. Limited psychological support at the contacted TB clinics was another experience reported. TB clinic staff's experiences confirmed almost all the experiences shared by their clients. With limited support, resilience and self-care were identified as key mechanisms for coping.
Conclusion
Complete recovery from PTB is possible, but reverting to a normal life is difficult without social support. Policies and programs need to increase opportunities for social support for TB patients and survivors. Doing so is likely to improve TB-related treatment, care-seeking practices, and adherence.
... Additionally, PTLD may lead to progressive airflow limitation, resembling chronic obstructive pulmonary disease or restrictive lung disease due to fibrotic changes. 4 Diagnosing PTLD poses several challenges, primarily due to its heterogeneous presentation and overlap with other respiratory conditions. Pulmonary function tests often reveal obstructive or restrictive patterns, reflecting the underlying lung damage. ...
... 7 Additionally, PTLD disproportionately affects socioeconomically disadvantaged populations, exacerbating existing health disparities. 4 Managing PTLD requires a comprehensive approach aimed at alleviating symptoms, preserving lung function, and preventing disease progression. Pharmacological interventions, such as inhaled bronchodilators, corticosteroids, and mucolytics, may help improve respiratory symptoms and reduce exacerbations. ...
... Pharmacological interventions, such as inhaled bronchodilators, corticosteroids, and mucolytics, may help improve respiratory symptoms and reduce exacerbations. 4 Pulmonary rehabilitation programs, including breathing exercises and physical therapy, can enhance exercise tolerance and quality of life. 8 Surgical interventions, such as lung volume reduction surgery or lung transplantation, may be considered in select cases with advanced disease. 4 Preventing PTLD begins with effective tuberculosis control measures, including early detection, prompt treatment initiation, and contact tracing to prevent transmission. ...
Post-tuberculosis lung disease (PTLD) presents a significant challenge in the management of tuberculosis patients, with far-reaching implications for global health. This editorial explores the multifaceted nature of PTLD, encompassing its pathophysiology, clinical manifestations, diagnostic complexities, and implications for public health. PTLD arises from pulmonary damage due to an active tuberculosis infection, leading to inflammation, scarring, and fibrosis within the lungs. Clinical manifestations vary widely, ranging from chronic respiratory symptoms to severe respiratory failure, often resembling chronic obstructive pulmonary disease or restrictive lung disease. The diagnosis of PTLD is hindered by its heterogeneous presentation and overlap with other respiratory conditions, necessitating a comprehensive evaluation through pulmonary function tests and radiological imaging. PTLD imposes a substantial burden on global health systems, particularly in regions with high tuberculosis prevalence, contributing to increased morbidity and mortality rates. Management strategies focus on alleviating symptoms, preserving lung function, and preventing disease progression through pharmacological interventions, pulmonary rehabilitation, and, in select cases, surgical interventions. Preventive measures include effective tuberculosis control measures, vaccination against respiratory pathogens, and addressing social determinants of health. Overall, a comprehensive understanding of PTLD is essential for improving patient outcomes and reducing disease burden, highlighting the importance of concerted efforts to raise awareness, enhance diagnostic capabilities, and develop effective management strategies for this complex condition.
... 9,10 This offers an opportunity for programmes to address key issues around the design and implementation of post-TB care in high TB incidence settings. 3,11,12 The working group focused on exploring four implementation questions considered of high priority for clinicians, health systems or the scientific community, with four working groups to explore these areas through discussion, evidence review and synthesis prior to the meeting, and through interaction with all symposium delegates within two workshops at the meeting itself ( Figure 2). Key messages 1-4 resulting from this work are briefly outlined below, with outputs to follow, including a review of NTP guidelines to understand current approaches to the investigation and management of symptomatic TB survivors, a logic framework outlining priority research areas for the implementation of post-TB care and a consensus research definition of PTLD. ...
... 34,35 Although other neurological sequelae of CNS and spinal TB such as seizures and motor, sensory and sphincter dysfunction are commonly encountered by clinician practitioners, their frequencies, severity and impact on patients' HRQoL are rarely reported. 11 Furthermore, evidence-based strategies to manage these complications are lacking. Patients with CNS and musculoskeletal TB are at increased risk of incurring catastrophic costs (i.e., spending at least 20% of annual household income on TB diagnosis and care) compared to patients with pulmonary TB, and these costs were discussed more fully in the ESP working group. ...
... This is indicative of increasing attention being paid to the well-being of TB survivors after completing TB treatment. Recent modelling studies, 2,48,49 the Clinical Standards for PTLD 12 and a consensus statement for post-TB health and well-being, 11 emphasise the ESP impact of PTLD. Emerging data suggest that TB survivors who describe residual respiratory symptoms also report progressive deterioration in general and disease-specific HRQoL, ongoing psychological distress, poor exercise capacity and dissaving (i.e., spending in excess of their current earnings). ...
In 2020, it was estimated that there were 155 million survivors of TB alive, all at risk of possible post TB disability. The 2 nd International Post-Tuberculosis Symposium (Stellenbosch, South Africa) was held to increase global awareness and empower TB-affected communities to play an active role in driving the agenda. We aimed to update knowledge on post-TB life and illness, identify research priorities, build research collaborations and highlight the need to embed lung health outcomes in clinical TB trials and programmatic TB care services. The symposium was a multidisciplinary meeting that included clinicians, researchers, TB survivors, funders and policy makers. Ten academic working groups set their own goals and covered the following thematic areas: 1) patient engagement and perspectives; 2) epidemiology and modelling; 3) pathogenesis of post-TB sequelae; 4) post-TB lung disease; 5) cardiovascular and pulmonary vascular complications; 6) neuromuscular & skeletal complications; 7) paediatric complications; 8) economic-social and psychological (ESP) consequences; 9) prevention, treatment and management; 10) advocacy, policy and stakeholder engagement. The working groups provided important updates for their respective fields, highlighted research priorities, and made progress towards the standardisation and alignment of post-TB outcomes and definitions.
... The disease is primarily driven by the development of a characteristic feature called granuloma formation which is mediated by the host immune cellular responses to the disease-causing pathogen 2,3 . Although the disease is curable with over 84% success rate, the affected individuals still suffer long lasting effects from the resultant pathology 1,4 . ...
... Furthermore, the pathology also contributes to reduced access to the site of infection by currently available TB drugs 5,6 . Because of this, TB therefore, contributes to a growing global burden of lung functions highlighting the need for earlier interventions to understand and prevent tissue damage, which contributes to diminishing lung function in affected individuals 4,7 . ...
Tuberculosis remains one of the major global health challenges with those previously exposed presenting persisting pulmonary dysfunction. Therefore, improved control measures are still required to prevent or reduce the TB-induced immunopathology in affected individuals. Host directed therapies that target host factors, have been suggested to improve on current treatments against TB. We previously reported a potential role for proteins which metabolizes the arachidonic acids during TB immunopathogenesis. The study, therefore, sort sought to demonstrate the potential role of these proteins in on TB-induced immunopathology. Using immune-histopathological assays, the association of macrophage driven ALOX5 signaling with severe pulmonary immunopathology during TB was demonstrated. Furthermore, using both in vitro and in vivo assays, the data demonstrated the contribution of ALOX5 signaling to TB-induced granulomatous inflammation. Interception of the signaling pathway through clinically approved pharmaceutical inhibitors, resulted in reduced lung damage during the disease. The resolution of TB-induced lung pathology further contributed to increased bactericidal activity. Taken together, our data strongly suggest a role for macrophage driven inflammation via ALOX5 signaling which can be targeted for the development of therapeutic treatment to prevent exacerbated TB-induced pulmonary immunopathology.
... The high burden of TB in this age group necessitates focused attention to adequately address its unique challenges and implications for child health and well-being. Despite the high burden of the disease, limited data are available globally on the morbidity of childhood TB and even less on the psychosocial consequences of TB [15,16]. Young children affected by respiratory illnesses face unique developmental and health-related challenges that are not adequately captured by tools designed for older populations. ...
... Globally, child mortality rates for those ≤ 5-years are significant, with particularly high rates in LMICs [23]. Additionally, children who were affected by TB or other respiratory illnesses often experience ongoing morbidity, underscoring the need for a measure to monitor their HRQoL over time [15]. We aimed to develop a comprehensive HRQoL item bank for children ≤ 5-years in an LMIC affected by respiratory illnesses through a three-step process, including a Delphi consensus study with experts, cognitive interviews, and stakeholder consultations. ...
Background
Health-related quality of life (HRQoL) is a crucial patient-centred outcome for developing policy. However, there is a lack of appropriate HRQoL measures for young children (0-5-years), who are particularly vulnerable to respiratory illnesses like pulmonary tuberculosis (PTB) and other respiratory infections, especially in low- and middle-income countries (LMICs). We aimed to develop a disease-specific HRQoL item bank for young children with acute and chronic respiratory illnesses.
Methods
An exploratory sequential design with three phases was used to develop a HRQoL item bank. The content validity of the item bank was evaluated by local and international experts specialising in HRQoL and child health. The group included paediatric pulmonologists, researchers with expertise in respiratory illnesses, and experts in scale development. Cognitive interviews with 37 caregivers of children with TB, pneumonia, adenovirus respiratory infection, other lower respiratory tract infections, reactive airway disease, and protracted bronchitis in Cape Town, South Africa, and consultations with 22 stakeholders were conducted for final revisions. The item bank was progressively refined at each phase of the study.
Findings
The Delphi experts recommended dividing the item bank into two age groups (0-2-years and 3-5-years) and using a 5-point Likert scale. Overall, 41 items (42%) met the predetermined > 70% threshold for inclusion in the item bank. Cognitive interviews confirmed that the domains were relevant. Minor modifications were made to five items in cohort 1 (0-2-years) and seven in cohort 2 (3-5-years), with 8 items (13%) and 14 items (22%) excluded. Phase 3 consultations emphasised the importance of including all seven domains and expanding the items to cover early childhood development, play, social interactions, and care routines. The final item bank includes versions for both age groups and incorporates these refinements.
Conclusion
An item bank was developed as a first step to develop a comprehensive disease-specific HRQoL tool for young children with respiratory illnesses in an LMIC. Input from caregivers and content experts was crucial in creating two HRQoL item banks tailored to the developmental differences between 0 and 2 and 3-5-year age groups. Their contributions ensured the tool effectively captures age-appropriate aspects of HRQoL. Future studies should focus on assessing the validity and reliability of these item banks.
... 4 These sequelae are likely a result of direct tissue damage caused by TB disease, the side effects of TB medications, the long-term mental health challenges experienced in relation to illness, social exclusion, stigma, patient costs and the economic impact of disease. [5][6][7][8] Chronic inflammation may also be experienced in relation to disease, leading to long-term cardiovascular morbidity. 9 The TB-associated disabilities most widely described in the literature include mental health disorders, and respiratory, musculoskeletal, hearing, visual, renal and neurological impairment, with a higher burden of morbidity experienced by those treated for drug-resistant compared to drug susceptible disease. ...
... Search terms were developed apriori and were informed by the terminology suggested in the consultation exercise above, key articles identified by the research team, and a recently published clinical statement on Post-TB health and wellbeing. 6 Duplicates were removed within intervention groups, but not between groups. ...
There is a growing body of data describing a high burden of respiratory morbidity amongst pulmonary TB patients and survivors, with up to half thought to experience residual respiratory symptoms, abnormal spirometry, or structural pathology after TB treatment completion. Many patients experiencing marked impacts on their lives and livelihoods. However, there remain no guidelines or evidence-based frameworks for integrated TB-respiratory care during or post TB treatment completion. In this scoping review, completed in collaboration with the WHO Global Tuberculosis Programme, we have identified a lack of primary data on the clinical efficacy, cost effectiveness or feasibility of six potential interventions for the prevention and management of TB-associated respiratory impairment and disability, with a lack of studies in children and adolescents. There is a need for robust interventional trials to improve the long-term respiratory outcomes of people affected by pulmonary TB disease, and to explore how these might be implemented within resource-limited settings.
... More than 10 million people worldwide fall ill with TB each year. In 2022, TB was the second leading infectious killer (after COVID- 19), and 1.3 million people died from TB. 1 However, TB is preventable and usually curable. Treatment success rates have increased to 88% for drug-susceptible TB and 63% for multidrug-resistant TB/rifampicin-resistant TB (MDR/RR-TB). 1 However, even after TB treatment completion, monitoring and clinical/functional assessment remain essential, as approximately one third of patients surviving pulmonary TB have post-TB lung disease (PTLD). ...
... 18 In fact, patients surviving TB face considerable ongoing morbidities besides PTLD, such as cardiac disorders, neurological impairments, psychosocial challenges and reduced health-related quality of life. 19 In this context, this issue of the Journal includes a paper by Allwood et al., which presents a summary of the proceedings of the 2 nd International Post-TB Symposium, held in Stellenbosch, South Africa. 20 The article describes what was discussed and the goals of 10 academic working groups (including those focused on PTLD, cardiovascular, neuromuscular/ skeletal and paediatric complications, among others). ...
... 2,3 While post-TB lung disease refers to consequences associated with pulmonary TB, post-TB sequelae are broader, encompassing sequelae that affect various organ systems and parts of the body beyond the pulmonary region. 4 These post-TB sequelae mainly arise from the disease process or the side effects related to TB treatment and increase the risk of permanent disability, premature mortality, ongoing stigma, and poor quality of life. 5 Previous systematic reviews on the global burden of TB-related disability showed that the prevalence of respiratory function impairment among TB survivors ranges from 15% to 60%. ...
... also important to mention that early diagnosis and appropriate treatment of TB are crucial in preventing post-TB pulmonary sequelae by halting disease progression, minimizing lung tissue damage, preventing drug resistance, and reducing the risk of TB complications. 4,45 A recent review showed that vaccination against respiratory tract infections including influenza, pneumococcal and COVID-19 potentially prevent post-TB lung sequelae. 46 The Brazilian Thoracic Association has also recommended the use of these vaccinations to prevent post-TB lung sequelae. ...
Background
Tuberculosis (TB) remains a global public health challenge, causing substantial mortality and morbidity. While TB treatment has made significant progress, it often leaves survivors with post-TB sequelae, resulting in long-term health issues. Current healthcare systems and guidelines lack comprehensive strategies to address post-TB sequelae, primarily due to insufficient evidence. This systematic review and meta-analysis aimed to identify effective interventions for preventing post-TB sequelae.
Methods
A systematic search was conducted across four databases including PubMed, SCOPUS, Web of Science, and Cochrane Central Register of Controlled Trials from inception to September 22, 2023. Eligible studies reported interventions designed to prevent post-TB sequelae were included. A random effect meta-analysis was conducted where applicable, and heterogeneity between studies was evaluated visually using forest plots and quantitatively using an index of heterogeneity (I²). This study is registered with PROSPERO (CRD42023464392).
Findings
From the 2525 unique records screened, 25 studies involving 10,592 participants were included. Different interventions were evaluated for different outcomes. However, only a few interventions were effective in preventing post-TB sequelae. Rehabilitation programs significantly improved lung function (Hedges's g = 0.21; 95% confidence interval (CI): 0.03, 0.39) and prevented neurological sequelae (relative risk (RR) = 0.10; 95% CI: 0.02, 0.42). Comprehensive interventions and cognitive-behavioural therapy significantly reduced the risk of mental health disorders among TB survivors (Hedges's g = −1.89; 95% CI: −3.77, −0.01). In contrast, interventions targeting post-TB liver sequelae, such as vitamin A and vitamin D supplementation and hepatoprotective agents, did not show significant reductions in sequelae (RR = 0.90; 95% CI: 0.52, 1.57). Moreover, adjunctive therapies did not show a significant effect in preventing post-TB neurological sequelae (RR = 0.62, 95% CI: 0.31, 1.24).
Interpretation
Rehabilitation programs prevented post-TB lung, neurologic and mental health sequelae, while adjuvant therapies and other interventions require further investigation.
Funding
Healy Medical Research Raine Foundation, Curtin School of Population Health and the Australian National Health and Medical Research Council.
... People on TB treatment do not always have good and sufficient information about their health status, what to expect during treatment, and how to take care of themselves. Further, people hear many myths about treatment and recovery [19]. To help people with TB promptly initiate the required therapy, it is important for them to receive evidence-based information [17]. ...
Background: Education and counselling of people with TB play an important role by instilling an understanding of risk factors and the impact of bad
habits, the skills necessary for a responsible attitude to one’s health, self-preservation behaviour, and, thus, initiating prompt treatment to a successful
completion — in other words, a cure.
Objective: This study attempts to investigate the influences of education and counselling on prompt initiation of treatment among people living with
tuberculosis in the Volta Region, Ghana. Methods: Descriptive cross-sectional design was employed with 400 participants. Frequency distribution,
Pearson’s chi-squared test of independence and binary logistic regression were used to analyse the data.
Results: Medication dosage was statistically significant related to prompt initiation of tuberculosis treatment at p=0.002, (OR=3.569, 95%CI ([1.604
7.942]). Appointment schedules and risk percentages was statistically significant at P=0.000, (OR=4.926, 95%CI [2.335-10.389]). Self-care, communication
and advocacy skills was statistically significant at p=0.02, (OR=3.569, 95%CI [1.604-7.942]).
Conclusion: The study recommends that patients should endeavour to join the education that goes on during hospital visit for it supports their access to
high-quality care, controls their overall healthcare spending and improves their literacy outcomes. It also allows them partner with their doctors in their
healthcare journey.
... Treating the accompanying depression is also an important part of TB management. Untreated depression can lead to persistent functional decline and a reduction in quality of life, even after TB treatment (35). In addition, this is because if depression accompanying in patients with TB is not treated, it may adversely affect results of TB treatment (36). ...
Background
Despite a high tuberculosis incidence in Korea, the association between tuberculosis and depression remains underexplored. This study aims to assess depression risk in tuberculosis survivors.
Methods
Utilizing South Korea’s National Health Insurance Sharing Service (NHISS) database, we conducted a gender-age-matched analysis comparing depression risk between tuberculosis survivors and the general population.
Results
This study included 137,996 participants, of whom 34,499 had tuberculosis history, and 103,497 age- and sex-matched individuals were selected as the control group. The risk of developing depression was higher in tuberculosis survivors than in the control group (aHR 1.20, 95% CI 1.15-1.25). In men, the risk of developing depression was 1.32 times (95% CI 1.25-1.39) compared with 1.05 times (95% CI 0.98-1.12) in women. Those taking para-aminosalicylate, cycloserine, and prothionamide had a higher risk of developing depression compared to those using other anti-tuberculosis drugs, with the risk ratio ranging from 1.27 to 1.61.
Conclusion
Tuberculosis survivors had a higher risk of developing depression compared to the control group. Although the prevalence of depression was higher in women compared to men, the risk of developing depression was higher in male tuberculosis survivors than in the control group, in contrast to the findings in women. The risk of developing depression in tuberculosis survivors differed depending on the anti-tuberculosis drug used and was mainly high in most of the second-line anti-tuberculosis drugs.
... Regardless of co-factors to TB implicated in chronic respiratory disease, past literature suggests that people who successfully complete TB treatment face higher long-term mortality rates despite successful treatment outcomes [7]. This suggests a need for patient follow-up beyond TB treatment completion and the consideration of respiratory diagnostic assessments to optimise lung health [17,18]. ...
Introduction
Post Tuberculosis Lung Disease (PTLD) is increasingly recognised as a significant cause of morbidity internationally, but has not been described in an Australian setting. We aimed to determine the prevalence of PTLD among adult TB survivors from an Australian TB service and describe the pattens of lung function abnormalities and pulmonary disease, including pulmonary hypertension.
Methods
We conducted a single-centre retrospective cohort study in Sydney, Australia, including all adults who successfully completed TB treatment between January 2013 and December 2022. Baseline characteristics, post treatment pulmonary function, and thoracic computed tomography (CT) data were analysed to determine the prevalence and patterns of PTLD, defined as any lung function and/or radiological abnormality attributable to TB.
Results
Among 119 confirmed TB patients (mean age 46 ± 21 years, 61% males) PTLD was identified in 81/119 (68%). Pulmonary function testing was available for 51/119 (43%), of whom 38/51(75%) exhibited abnormalities. Obstructive deficits were found in 25/51 (49%), restrictive deficits in 11/51 (22%), and impaired gas transfer capacity in 26/51 (51%). Chest CT scans were completed in 76/119 (64%), with 70/76 (92%) demonstrating significant abnormalities, including pulmonary fibrosis 43/76 (57%), bronchiectasis 22/76 (29%), and emphysema 11/76 (15%). Pulmonary hypertension was suspected in 52/76 (68%) patients based on radiological findings.
Conclusion
Despite successful treatment, PTLD was frequently observed among our cohort of Australian TB survivors. Further research into optimal screening practices to diagnose chronic pulmonary diseases and pulmonary hypertension could provide opportunities for earlier intervention and management.
... Schizoaffective disorder is reported in approximately 30% of cases between the ages of 25-35 years, with a higher prevalence in women at around 0.3% [16]. However, large-scale studies on the epidemiology, incidence, and prevalence of schizoaffective disorder remain limited. ...
Adolescents are vulnerable to tuberculosis (TB), some with severe forms like miliary TB, due to biological, psychosocial, and environmental factors. Schizoaffective disorder, though rare, adds complexity to TB management, requiring a multidisciplinary approach. This report aims to describe the comprehensive management of a 17-year-old female with miliary TB, anti-tuberculosis drug-induced hepatotoxicity (ADIH), and schizoaffective disorder, emphasizing the interplay between infectious disease and mental health. A 17-year-old female presented with shortness of breath, chronic cough, prolonged fever, and weight loss. Diagnosed with miliary TB via GeneXpert MTB/RIF testing and imaging, she was treated with first-line anti-tuberculosis drugs. On day 12, the patient developed ADIH, necessitating temporary discontinuation of particular anti-tuberculosis drugs and gradual reintroduction of therapy. Concurrent psychological evaluations revealed schizoaffective disorder, managed with psychiatric medication and counseling. Over 12 months, the patient exhibited clinical and psychological improvements, supported by family involvement and environmental adjustments. Integrated medical and psychosocial strategies are required in managing complex TB cases. Addressing comorbid mental health conditions and fostering a supportive environment is crucial for optimizing outcomes. The findings highlight the comprehensive management of complex TB and schizoaffective disorder using pharmacological and psychological therapy.
... In a recent clinical statement on post-TB health and wellbeing, the authors evaluated the psychosocial and socioeconomic effects in TB survivors. Poor HRQoL in PTLD patients is associated with impaired social life, economic losses, and persistent symptoms (25). The decrease in physical capacity resulting from chronic respiratory diseases impacts the economy and families' livelihoods (26). ...
Background
Brazil remains one of the 30 countries with the highest tuberculosis (TB) and TB-HIV coinfection burden. Post-TB lung disease (PTLD) is a set of sequelae that can occur in people who have been cured of TB.
Aim
To learn about the experiences of people living with PTLD (PLPTLD) and how healthcare workers (HCW) manage PTLD.
Methods
An exploratory qualitative study with a purposive sample of PLPTLD and HCW from two different cities. Open-ended interviews were conducted using a semi-structured interview guide, which were recorded and transcribed. Two researchers analyzed the interviews using an inductive approach and applied a content analysis framework to define categories.
Results
Forty-six participants were interviewed, and four categories emerged: PTLD as a social disease; stigma; the fragility of access; and limitations. The categories encompassed two main aspects like PTLD in activities of daily living and emotions in everyday life, for instance, challenges with preparing meals, getting a job, barriers to set clinical appointments or getting social assistance, and stigma.
Conclusion
This study reveals specific needs from patients and providers such as a lack of knowledge about PTLD, physical limitations, and stigmatization due to PTLD. It is crucial to address these issues in public health policies.
... 3 Although antibiotic treatment can be successful in averting death, there is evidence of long-term sequelae and an elevated mortality risk among TB survivors. [4][5][6] Historically, TB research efforts have focused on alleviating the acute phase of the disease. Although there has been recent consideration of the consequences during the post-acute phase, this area of study is still in its infancy. ...
Background
Post-tuberculosis (TB) sequelae present a significant challenge in the management of TB survivors, often leading to persistent health issues even after successful treatment. Identifying risk factors associated with post-TB sequelae is important for improving outcomes and quality of life of TB survivors. This systematic review and meta-analysis aims to identify risk factors associated with long-term physical sequelae among TB survivors.
Methods
We systematically searched Medline, Embase, PROQUEST, and Scopus for studies on long-term physical sequelae among TB survivors up to December 12, 2023. The primary outcome of interest was to quantify risk factors of long-term physical sequelae (i.e., respiratory, hepatic, hearing, neurological, visual, renal, and musculoskeletal sequelae). We included all forms of TB patients who experienced long-term physical sequelae. We used narrative synthesis for risk factors reported once and random-effect meta-analysis for primary outcomes with two or more studies. Findings were presented with odds ratios (OR) and 95% confidence intervals (CI). Publication bias was assessed using funnel plots and Egger regression, and heterogeneity was examined with a Galbraith radial plot. The protocol was registered on Prospero (CRD42021250909).
Findings
A total of 73 articles from 28 countries representing 31,553 TB-treated patients were included in the narrative synthesis, with 64 of these studies included in the meta-analysis. Risk factors associated with post-TB lung sequelae include older age (OR = 1.62, 95% CI: 1.07–2.47), previous TB treatment history (OR = 3.43, 95% CI: 2.37–4.97), smoking (OR = 1.41, 95% CI: 1.09–1.83), alcohol consumption (OR = 1.84, 95% CI: 1.04–3.25), smear-positive pulmonary TB diagnosis (OR = 3.11, 95% CI: 1.77–6.44), and the presence of radiographic evidence of pulmonary lesions at the commencement of treatment (OR = 2.04, 95% CI: 1.07–3.87). Risk factors associated with post-TB liver injury included pre-existing hepatitis (OR = 2.41, 95% CI: 1.16–6.08), previous TB treatment (OR = 2.64, 95% CI: 1.22–6.67), hypo-albuminemia (OR = 2.10, 95% CI: 1.53–2.88), HIV co-infection (OR = 2.72, 95% CI: 1.66–4.46), and CD4 count <200 mm³ in HIV-infected individuals (OR = 2.03, 95%CI: 1.26–3.27). Risk factors associated with post-TB hearing loss include baseline hearing problems (OR = 1.72, 95% CI: 1.30–2.26), and HIV co-infection (OR = 3.02, 95% CI: 1.96–4.64).
Interpretation
This systematic review and meta-analysis found that long-term physical post-TB sequelae including respiratory, hepatic, and hearing impairment were associated with a range of socio-demographic, behavioral, and clinical factors. Identification of these risk factors will help to identify patients who will benefit from interventions to reduce the burden of suffering from post-TB treatment.
Funding
Healy Medical Research Raine Foundation, the Australian National Health and Medical Research Council, and 10.13039/501100001797Curtin University Higher Degree Research Scholarship fund the study.
... Therefore, a regimen of 6 months was highly recommended by World Health Organization (WHO) guidelines (WHO, 2023). Although death is preventable by successful treatment, a great number of TB survivors experience post-tuberculosis conditions, with an increase of long-term disability evidence in this population (Nightingale et al., 2023). The burden of Frontiers in Cellular and Infection Microbiology frontiersin.org ...
... One key example of such factors is stigma, which has various consequences including delayed treatment-seeking, avoidance of disclosure of TB status, poor treatment adherence, and poor quality of life [7][8][9][10]. Additionally, TB may exert downstream effects even after treatment completion -for example common post-TB sequelae, such as neurological and cardiovascular impairment, as well as reduced social and psychological wellbeing, have an impact beyond resolution of the disease itself, and stigma can persist even after treatment has been completed [11,12]. Successful policies to eliminate TB and prevent drug resistance must therefore address such factors, with stigma and self-stigma (or internalised stigma) being noted as important targets that are relatively under-explored in terms of intervention [13,14]. ...
Background
Self-stigma among people who have tuberculosis (TB) can contribute to non-adherence to medication and disengagement from care. It can manifest in feelings of worthlessness, shame, and guilt, leading to social withdrawal and disengagement from life opportunities. Self-stigma may also affect families of those who have TB, or healthcare workers who treat them. However, few interventions addressing TB self-stigma exist to date.
Methods
We piloted the delivery of a toolkit of psychosocial interventions using a “training-of-trainers” approach with six staff members of a TB-focused NGO (Non-Governmental Organisation) and partner organisations in Jakarta, Indonesia. These trainers could then disseminate the toolkit among community partner organisations. Local staff involvement throughout the study supported translation and adaptation to enhance cultural and language appropriateness. Over a 2-day training-of-trainers workshop, the NGO staff were familiarised with the mode of delivery of the toolkit, which they then delivered via a four-day participatory workshop with 22 people who have TB/TB survivors, who were representatives of partner organisations working among communities affected by TB.
Results
The newly-trained local facilitators delivered the toolkit to the participants, who self-reported significant increases in knowledge and efficacy around TB self-stigma post-intervention compared to baseline (Z = 1.991, p = 0.047, Wilcoxon signed-rank test). The participants’ levels of self-compassion were also significantly higher post-workshop (Z = 2.096, p = 0.036, Wilcoxon signed-rank test); however, these effects were not maintained at 3-month timepoint. There was also a significant increase post-workshop in one of the participants’ Ryff dimensions of psychological wellbeing, that of positive relationships with others (Z = 2.509, p = 0.012, Wilcoxon signed-rank test) but this was also not maintained at the 3-month timepoint.
Conclusions
The observed changes in recipients’ self-reported levels of knowledge and efficacy, self-compassion, and psychological wellbeing may warrant further investigation into the best modalities for toolkit delivery (frequency, dose, duration) and support for individuals as they progress through the TB treatment journey.
... 10,11 It remains unclear who is at the highest risk for TB-associated respiratory disability. Consequently, guidelines recommend screening all pulmonary TB survivors for TB-associated respiratory disability, [12][13][14] a practice that is not feasible in the resource-limited settings where the majority of TB survivors reside. 1,2 An improved understanding of risk factors and epidemiological determinants of TB-associated respiratory disability is crucial to enhancing the efficiency and feasibility of screening. ...
Background
Approximately 2% of the global population has survived tuberculosis (TB). Increasing evidence indicates that a significant proportion of pulmonary TB survivors develop TB-associated respiratory disability, commonly referred to as post-TB lung disease (PLTD) and marked by impaired respiratory function, persistent symptoms, and activity limitations. However, the prevalence, risk factors, and progression of TB-associated respiratory disability throughout the life course are not well understood. To address these gaps, we will undertake a systematic review and individual participant-level data meta-analysis (IPD-MA) focusing on TB-associated respiratory disability in children, adolescents, and adults successfully treated for pulmonary TB.
Methods and analysis
We will systematically search MEDLINE, Embase, CENTRAL, Global Index Medicus, and medRxiv for original studies investigating TB-associated respiratory disability in people of all ages who have completed treatment for microbiologically confirmed or clinically diagnosed pulmonary TB. Authors of eligible studies will be invited to contribute de-identified data and form a collaborative group. Primary outcomes will be (1) abnormal lung function based on spirometry parameters and (2) chronic respiratory symptoms. We will estimate the overall and subgroup-specific prevalence of each outcome through IPD meta-analysis. Next, we will develop clinical prediction tools assessing the risk of future TB-associated respiratory disability at (i) the start of TB treatment and (ii) end of TB treatment for those without existing signs of disability. Finally, we will use stepwise hierarchical modelling to identify epidemiological determinants of respiratory disability.
Ethics and dissemination
This study has been approved by the ethics review boards at the Rhode Island Hospital (2138217-2) and the Research Institute of the McGill University Health Centre (2024-10345). Individual study authors will be required to obtain institutional approval prior to sharing data. Results will be disseminated through open-access, peer-reviewed publications and conference presentations.
Prospero registration number
CRD42024529906
... There has been on-going clinical research on TBM in the Western Cape province, South Africa, since 1985 [7], including diagnostic, neurophysiological, treatment and operational research studies [8][9][10][11]. TBM has been reported as the most common form of bacterial [13]. Another tertiary referral hospital reported that 90% (40/44) of patients presented with Stage II or III TBM, with a mortality rate of 16% (7/44) [14]. ...
Tuberculous meningitis (TBM) occurs when tuberculosis (TB) bacilli disseminate and seed into the meninges, triggering a severe inflammatory response that often leads to brain infarction. It is the most severe and debilitating form of childhood TB with high mortality, and children who survive TBM often suffer lifelong physical and neuro-disability resulting in emotional, social, and economic burdens for families. In the early stages the symptoms may be non-specific and so the diagnosis is often made late when the patient already has significant brain injury. To facilitate earlier diagnosis, it is important to understand how patients are evaluated. This study aimed to chart health systems for paediatric TBM care at both primary healthcare (PHC) and hospital level in Cape Town, South Africa. We conducted fourteen in-depth interviews and eight days of semi-structured observations of patient flow across eight healthcare facilities. We found that children with TBM navigate multiple levels of care categorised into pre-admission and primary care, hospital admission and inpatient care, and post-discharge follow-up care. Healthcare workers identified the following health system barriers along the TBM care pathway for children: limited post-training and mentorship opportunities to manage TBM, overburdened facilities, time constraints, lack of recognition of TBM symptoms, delays in referral between PHC and hospital, lack of standardized diagnostic algorithms, limited diagnostic tests and a lack of child-friendly, easy-to-administer treatment. Regular and compulsory training on TB and TBM in children, including continuous mentoring and support to healthcare workers working in child health and TB services in high TB-burden settings, can facilitate early recognition of symptoms and rapid referral for diagnosis. Algorithms outlining referral criteria for patients with possible TBM at both PHC facilities and district level hospitals can guide healthcare providers and facilitate timely referral between different levels of healthcare services. An integrated data system and alert functions could flag multiple healthcare visits and improve communication between different healthcare facilities during diagnosis and treatment. Children and families affected by TBM are an especially vulnerable sub-population requiring high priority attention and support.
... [9][10][11] This collection of persistent sequelae-collectively known as post-TB lung disease (PTLD)-has drawn increasing scientific and policy attention. 12,13 Mathematical modelling is commonly used to extrapolate from clinical studies to estimate long-term population-level outcomes, 14 with these analyses reproducing key features of TB epidemiology and natural history. 15,16 In many published TB models, active disease is represented by a single disease state, sometimes stratified to capture differences in diagnostic test results (e.g., sputum-smear positivity). ...
Background: Untreated pulmonary tuberculosis (TB) causes ongoing lung damage, which may persist after treatment. Conventional approaches for assessing TB health effects may not fully capture these mechanisms. We evaluated how TB–associated lung damage and post–TB sequalae affect the lifetime health consequences of TB in high HIV prevalence settings.
Methods: We developed a microsimulation model representing dynamic changes in lung function for individuals evaluated for TB in routine clinical settings. We parameterized the model with data for Uganda, Kenya, and South Africa, and estimated lifetime health outcomes under prompt, delayed, and no TB treatment scenarios. We compared results to earlier modelling approaches that omit progressive lung damage and post–TB sequelae.
Findings: We estimated 4.6 (95% uncertainty interval 3.4–5.8), 7.2 (5.1–9.6), and 18.0 (15.1–20.0) year reductions in life expectancy due to TB under prompt, delayed, and no treatment scenarios, respectively. Disability–adjusted life years (DALYs) from TB were estimated as 8.3 (6.2–10.6), 12.6 (9.0–17.0), and 27.8 (24.1–30.6) under prompt, delayed, and no treatment scenarios, respectively. Post–TB DALYs represented 9–53% of total DALYs. Modelling approaches that omit progressive lung damage and post–TB sequelae underestimated lifetime health losses of TB by 48–57%, and underestimated the benefits of prompt treatment by 45–64%.
Interpretation: Delayed initiation of TB treatment causes greater lung damage and higher mortality risks during and after the disease episode. In settings with co–prevalent TB and HIV, accounting for these factors substantially increased estimates of the lifetime disease burden and life expectancy loss caused by TB.
Funding: NIH.
... Bronchodilators, including short-acting beta-agonists (SABAs) and long-acting beta-agonists (LABAs), are commonly used to alleviate bronchospasm and improve airflow in patients with concomitant bronchial hyperreactivity. Inhaled corticosteroids (ICS) may be prescribed to reduce airway inflammation and minimize exacerbations, particularly in patients with evidence of eosinophilic inflammation or asthma-like symptoms [4,20]. ...
Post-tuberculosis lung disease (PTLD) poses a significant clinical challenge in regions with a high burden of tuberculosis (TB). This review provides a comprehensive overview of PTLD, encompassing its pathogenesis, clinical manifestations, diagnostic modalities, management strategies, long-term outcomes, and public health implications. PTLD arises from residual lung damage following TB treatment and is characterized by a spectrum of pathological changes, including fibrosis, bronchiectasis, and cavitation. Clinical presentation varies widely, from chronic cough and hemoptysis to recurrent respiratory infections, which are oftentimes a diagnostic dilemma. Radiological imaging, pulmonary function tests, and careful consideration of patient history play pivotal roles in diagnosis. Management strategies involve pharmacological interventions to alleviate symptoms and prevent disease progression, which are influenced by the extent of lung damage, comorbidities, and access to healthcare. Rehabilitation programs and surgical options are available for select cases. Prognosis is influenced by the extent of lung damage, comorbidities, and access to healthcare. Prevention efforts through a TB control program and early detection are crucial in reducing the burden of PTLD. This review stresses the importance of understanding and addressing PTLD to mitigate its impact on individuals and public health systems worldwide.
... Even though up to 85% of persons treated for new pulmonary TB (pTB) achieve treatment success, the issues of potentially long-lasting consequences for the health and well-being of TB survivors have recently gained increasing attention. [2][3][4][5] Emerging evidence from mostly adult studies has suggested that people previously treated for pTB continue to experience long-term respiratory impairment even years after successful treatment, leading to substantial post-TB morbidity and mortality. [6][7][8][9] Therefore, it is equally important to evaluate respiratory health and overall wellbeing after TB treatment in children and adolescents who are in a critical period of their lung development. ...
Background
Although post‐tuberculosis lung disease (PTLD) is a known consequence of pulmonary tuberculosis (pTB), few studies have reported the prevalence and spectrum of PTLD in children and adolescents.
Methods
Children and adolescent (≤19 years) survivors of pTB in the Western Regions of The Gambia underwent a respiratory symptom screening, chest X‐ray (CXR) and spirometry at TB treatment completion. Variables associated with lung function impairment were identified through logistic regression models.
Results
Between March 2022 and July 2023, 79 participants were recruited. The median age was 15.6 years (IQR: 11.8, 17.9); the majority, 53/79 (67.1%), were treated for bacteriologically confirmed pTB, and 8/79 (10.1%) were children and adolescents living with HIV. At pTB treatment completion, 28/79 (35.4%) reported respiratory symptoms, 37/78 (47.4%) had radiological sequelae, and 45/79 (57.0%) had abnormal spirometry. The most common respiratory sequelae were cough (21/79, 26.6%), fibrosis on CXR (22/78, 28.2%), and restrictive spirometry (41/79, 51.9%). Age at TB diagnosis over ten years, undernutrition and fibrosis on CXR at treatment completion were significantly associated with abnormal spirometry ( p = .050, .004, and .038, respectively).
Conclusion
Chronic respiratory symptoms, abnormal CXR, and impaired lung function are common and under‐reported consequences of pTB in children and adolescents. Post‐TB evaluation and monitoring may be necessary to improve patient outcomes.
... 100 Review associated with DR-TB are often far greater than those observed in drug-susceptible disease and might persist for years after treatment completion. 1,2,103,104 Globally, 81% of families affected by DR-TB incur costs related to tuberculosis that exceed 20% of their household income. 1,2 In South Africa, these costs are far-reaching, tied to lost income from patients' inability to work and lost household productivity for patients and their caregivers. ...
... Long-term follow-up is essential in TB arthritis to assess treatment efficacy, monitor for disease recurrence, and manage potential sequelae such as joint deformities or functional impairments. Multidisciplinary care teams play a crucial role in providing comprehensive patient management throughout the treatment course [17]. ...
We present a case report of a 66-year-old male patient with a known history of leprosy who presented with pain and swelling in his right foot for the past 1.5 years. Fine needle aspiration cytology (FNAC) revealed non-inflammatory exudate, and Mycobacterium tuberculosis (MTB) was identified in the sample by the cartridge-based nucleic acid amplification test (CBNAAT). The patient was managed conservatively with anti-Koch's treatment (AKT), and a follow-up was conducted for 12 months to monitor the treatment response and overall progress. This highlights the importance of early diagnosis and appropriate medical management, along with a long-term follow-up, among patients with ankle tuberculosis, to reduce the need for surgical intervention.
... As such, understanding its effect on quality of life and health status is essential for patient care, evaluation of novel treatments or development of preventive strategies, and health policy [1]. Although it has been effectively treated for many years, and progress has been made in prevention and care, it still represents a global health problem for which the conditions and outcomes valued by the TB community need to be better understood [2]. Identifying patient-reported outcomes (PROs) reported by people affected by TB can provide a wealth of information about the impact of the disease. ...
Patient-reported outcomes (PROs) play a crucial role in understanding the impact of tuberculosis (TB) on both individuals and communities. Despite advances in TB treatment, conventional outcome definitions often overlook essential components of people with TB's experiences, leading to disparities in treatment understanding. The incorporation of PROs in TB scientific research can help bridge the gap between the health system and people's needs and expectations. PROs can offer valuable insights into non-observable constructs like health literacy, self-efficacy and overall wellbeing, contributing to the comprehensive assessment of diagnosis, treatment and research end-points. Participatory community approaches, such as Community-Based Participatory, emphasise the engagement and involvement of relevant stakeholders in designing interventions tailored to their needs. Key stakeholders, including healthcare professionals, researchers, clinical trial investigators, public health officials, and community health workers, TB survivors and people with TB, can play a vital role in promoting patient-centred care and engaging directly with the TB-affected community. An increased and cross-collaborative effort for the inclusion of PROs in TB research can entail their potential role in developing effective treatment regimens and promoting adherence, while maximising community engagement and improving outcomes for those affected by TB.
... Dear Editor, We read with interest the first of the IJTLD Clinical Standards on Lung Health on the topic of 'Clinical standards for the assessment, management and rehabilitation of post-TB lung disease' and related papers on post-TB lung disease (PTLD). [1][2][3] Here, we report on the unique experience of Brazil, which is the first country to produce national guidelines on PTLD. The guidelines have been developed by the Sociedade Brasileira de Pneumologia e Tisiologia (SBPT), which in early 2023, created a national committee (including international experts), drafted the guidelines and in August 2023 approved them during the SBPT Conference in Curitiba. ...
... This is the pattern we have seen to date, with OA articles in the IJTLD typically having the highest number of downloads and citations. [11][12][13] OA also has societal benefits, with improved awareness and understanding of respiratory disease for all concerned. In this way, we can address issues such as stigma, and promote greater access to treatment, helping to remove barriers to improved healthcare. ...
Editorial in the launch issue of IJTLD OPEN to highlight the benefits of open access for authors and for readers (especially those in low to middle income countries).
Tuberculosis (TB) remains a significant global health threat with high mortality and efforts to meet WHO End TB Strategy milestones are off‐track. It has become clear that TB is not a dichotomous infection with latent and active forms but presents along a disease spectrum. Subclinical TB plays a larger role in transmission than previously thought. Aerosol studies have shown that undiagnosed TB patients, even with paucibacillary disease, can be highly infectious and significantly contribute to TB spread. Encouraging clinical results have been seen with the M72/AS01 E vaccine. If preliminary results can be confirmed in ongoing larger trials, modelling shows the vaccine can positively impact the epidemic. TB preventive therapy (TPT), especially for high‐risk groups like people living with HIV and household contacts of drug‐resistant TB patients, has shown efficacy but implementation is resource intensive. Treatment options for infectious patients have grown rapidly. New shorter, all‐oral treatment regimens represent a breakthrough, but progress is threatened by rising resistance to bedaquiline. Many new chemical entities are entering clinical trials and raise hopes for all‐new regimens that could overcome rising resistance rates to conventional agents. More research is needed on the management of complex cases, such as central nervous system TB and severe HIV‐associated TB. Post‐TB lung disease (PTLD) is an under‐recognised but growing concern, affecting millions of survivors with lasting respiratory impairment and increased mortality. Continued investment in development of TB vaccines and therapeutics, treatment shortening, and management of TB sequelae is critical to combat this ongoing public health challenge.
O estudo objetiva analisar os fatores de risco associados ao óbito pela coinfecção HIV/Tuberculose no estado de Pernambuco, no período entre 2008 e 2011. Foi realizado um estudo de corte transversal, com todos os casos de óbitos por HIV e/ou Tuberculose com base nos dados do Sistema de Informação sobre Mortalidade, fornecidos pelo Setor de Vigilância Epidemiológica da Secretaria Estadual de Saúde. Os dados foram analisados com o auxílio do programa estatístico SPSS 28.0. O estudo foi aprovado pelo Comitê de Ética em Pesquisa do Centro de Ciências da Saúde da Universidade Federal de Pernambuco, sob o número 004184/2013. A prevalência da mortalidade pela coinfecção HIV/TB foi de 11,1% (IC95%: 10,13 - 12,21). Permaneceram como fatores de risco independentes para óbito por HIV/TB, a cor da pele não branca, estado civil solteiro e a escolaridade > 9 anos. Os resultados ressaltam a necessidade de se adotar medidas mais eficazes para diminuir a taxa de TB entre os infectados pelo HIV, sendo importante a realização da sorologia para HIV em todos os pacientes que estejam em tratamento para a TB. Ampliar a busca ativa em casos de baixa adesão ao tratamento da TB, uso de esquemas terapêuticos baseados em antibióticos de última geração para combater infecções resistentes e estratégias integradas de prevenção e controle das duas doenças, passando a tratá-las de forma conjunta, e não separada.
It is now well understood that the effect of TB does not always end when a patient completes a successful course of treatment. Successful treatment is by definition a microbiological cure, but people may continue to suffer the consequences of TB for months or years after treatment. For example, ongoing health challenges can present in the form of post-TB lung disease (PTLD), and there is a high incidence of TB-related symptoms associated with disability in other domains. We discuss an article in this issue of the Journal that explores the experiences of adult TB survivors, which further expands our understanding of this condition.
BACKGROUND
Growing evidence suggests that post-TB-related morbidity occurs often among TB survivors, but there is limited epidemiological data on the burden of symptoms and disability after successful completion of treatment. We evaluated the prevalence of TB-related symptoms, self-reported disability, and factors associated with disability among adult TB survivors who recently completed treatment in Uganda.
METHODS
Between January 2022 and October 2023, we conducted a study of adults who completed treatment for drug-susceptible TB in Kampala, Uganda. We collected data on demographics, TB-related symptoms, HIV status, and disability measured using the World Health Organization Disability Assessment Schedule (WHODAS 2.0).
RESULTS
Of the 200 participants, the median age was 33.0 years (IQR 26–44.5); 52.5% were male, and 23% were HIV-infected. The prevalence of TB symptoms was 58%, and self-reported disability was 83.5%. Factors significantly associated with disability were having completed treatment within the last 6–8 months and experiencing TB symptoms (aOR 2.87, P = 0.04; and aOR 2.51, P = 0.03, respectively), after adjusting for age, sex and HIV status.
CONCLUSIONS
TB-related symptoms and self-reporting of any disability were highly prevalent in the study population. There is a need for further longitudinal evaluation and considerations to expand the continuum of care and support to improve the quality of life for TB survivors post-TB treatment.
BACKGROUND
Respiratory illnesses, including pulmonary TB (PTB), cause significant morbidity. We aimed to understand the health-related quality of life (HRQoL) of children with presumptive PTB.
METHODS
Children aged 0–13 years presenting with presumptive PTB were enrolled. This study includes children who started TB treatment and children in whom TB was excluded (symptomatic controls). Quantitative data were collected using the Toddler and Infant quality of life Instrument (TANDI) (<3 years) and European Quality of Life-5 Dimensions-Youth (EQ-5D-Y) (>3 years) measures. Qualitative data were collected through in-depth interviews using thematic analysis.
RESULTS
Quantitative data from caregivers of 201 children (TANDI: n = 170; EQ-5D-Y: n = 31) showed 77 (38.3%) were diagnosed with TB, while 124 (61.7%) were symptomatic controls. Qualitative data from 15 caregivers of 21 children included 10 (67%) children with TB and 5 (33%) symptomatic controls. The median TANDI Visual Analogue Score (VAS) for overall health was 90% (IQR 80–100); the EQ-5D-Y VAS median was 95% (IQR 80–100). Caregivers described decreased energy, difficulty eating, and increased sleep using qualitative interviews, which were not reflected in the quantitative data. No differences were found between children with TB and symptomatic controls.
CONCLUSIONS
HRQoL was high in children with TB, but discrepancies between quantitative and qualitative measures highlight the limitations of the current HRQoL measures.
Extract
Transmission continues to drive the tuberculosis (TB) and drug-resistant TB epidemics, making infection control an essential component for public health agencies worldwide [1–3]. Transmission of TB is complex, influenced by factors linked to patient behaviour, the form of disease, the exposed individual, the microbe and the environment [3–6]. Each year, more than 10 million people develop TB, more than 80% of whom have pulmonary disease and more than 60% are bacteriologically positive [1].
Tuberculosis (TB) is an important cause of morbidity and mortality globally. About 3–4% of hospitalized TB patients require admission to the intensive care unit (ICU); the mortality in these patients is around 50–60%. There is limited literature on the evaluation and management of patients with TB who required ICU admission. The Indian Society of Critical Care Medicine (ISCCM) constituted a working group to develop a position paper that provides recommendations on the various aspects of TB in the ICU setting based on available evidence. Seven domains were identified including the categorization of TB in the critically ill, diagnostic workup, drug therapy, TB in the immunocompromised host, organ support, infection control, and post-TB sequelae. Forty-one questions pertaining to these domains were identified and evidence-based position statements were generated, where available, keeping in focus the critical care aspects. Where evidence was not available, the recommendations were based on consensus. This position paper guides the approach to and management of critically ill patients with TB.
How to cite this article
Chacko B, Chaudhry D, Peter JV, Khilnani G, Saxena P, Sehgal IS, et al. isccm Position Statement on the Approach to and Management of Critically Ill Patients with Tuberculosis. Indian J Crit Care Med 2024;28(S2):S67–S91.
BACKGROUND
We examined the feasibility of assessing and referring adults successfully completing TB treatment for comorbidities, risk determinants and disability in health facilities in Kenya, Uganda, Zambia and Zimbabwe.
METHODS
This was a cross-sectional study within national TB programmes.
RESULTS
Health workers assessed 1,063 patients (78% of eligible) in a median of 22 min [IQR 16–35] and found it useful and feasible to accomplish in addition to other responsibilities. For comorbidities, 476 (44%) had HIV co-infection, 172 (16%) had high blood pressure (newly detected in 124), 43 (4%) had mental health disorders (newly detected in 33) and 36 (3%) had diabetes mellitus. The most common risk determinants were ‘probable alcohol dependence’ (15%) and malnutrition (14%). Disability, defined as walking <400 m in 6 min, was found in 151/882 (17%). Overall, 763 (72%) patients had at least one comorbidity, risk determinant and/or disability. At least two-thirds of eligible patients were referred for care, although 80% of those with disability needed referral outside their original health facility.
CONCLUSIONS
Seven in 10 patients completing TB treatment had at least one comorbidity, risk determinant and/or disability. This emphasises the need for offering early patient-centred care, including pulmonary rehabilitation, to improve quality of life, reduce TB recurrence and increase long-term survival.
Background . Despite the visible successes of domestic phthisiology at the present time, the problem of medical rehabilitation of patients with tuberculosis remains relevant. In recent years, approaches to medical rehabilitation of patients with various diseases have changed significantly, which entail the need to consider a complex of rehabilitation measures for patients with tuberculosis from the perspective of the Procedures for organizing medical rehabilitation in adults and children and their integration into phthisiatric practice.
The aim . To study the organizational aspects of medical rehabilitation of patients with respiratory tuberculosis in the world and the Russian Federation.
Methods . We carried out an analysis of domestic and foreign literature, regulatory documents on the organization of rehabilitation for tuberculosis patients for 2018–2023 in electronic databases PubMed/Medline, Google Scholar using terms “tuberculosis, pulmonary/rehabilitation” in English and Russian languages.
The results show a growing amount of factual information demonstrating the positive effect of pulmonary rehabilitation in patients with respiratory diseases, including tuberculosis. The analysis revealed defects in the organization of the medical rehabilitation system in the structure of medical care for tuberculosis patients in the Russian Federation. This concerns problems of routing, phasing, organizational models, human and material resources, standardization of the main components of the rehabilitation process, the significance and effectiveness of certain rehabilitation measures, which leads to low availability of rehabilitation care for tuberculosis patients. Deficiencies in the regulatory framework prevent the integration of medical rehabilitation into the practice of TB services.
Conclusion . Modern issues of organizing rehabilitation care for patients with tuberculosis require further study and improvement. The development of a system of medical rehabilitation of patients with tuberculosis helps to increase the effectiveness of treatment, to reduce the number of complications, disability, mortality due to tuberculosis, and to increase the duration and quality of life of patients.
Introduction
Despite growing evidence of the long-term impact of tuberculosis (TB) on quality of life, Global Burden of Disease (GBD) estimates of TB-related disability-adjusted life years (DALYs) do not include post-TB morbidity, and evaluations of TB interventions typically assume treated patients return to pre-TB health. Using primary data, we estimate years of life lost due to disability (YLDs), years of life lost due to premature mortality (YLL) and DALYs associated with post-TB cardiorespiratory morbidity in a low-income country.
Methods
Adults aged ≥15 years who had successfully completed treatment for drug-sensitive pulmonary TB in Blantyre, Malawi (February 2016–April 2017) were followed-up for 3 years with 6-monthly and 12-monthly study visits. In this secondary analysis, St George’s Respiratory Questionnaire data were used to match patients to GBD cardiorespiratory health states and corresponding disability weights (DWs) at each visit. YLDs were calculated for the study period and estimated for remaining lifespan using Malawian life table life expectancies. YLL were estimated using study mortality data and aspirational life expectancies, and post-TB DALYs derived. Data were disaggregated by HIV status and gender.
Results
At treatment completion, 222/403 (55.1%) participants met criteria for a cardiorespiratory DW, decreasing to 15.6% after 3 years, at which point two-thirds of the disability burden was experienced by women. Over 90% of projected lifetime-YLD were concentrated within the most severely affected 20% of survivors. Mean DWs in the 3 years post-treatment were 0.041 (HIV-) and 0.025 (HIV+), and beyond 3 years estimated as 0.025 (HIV-) and 0.010 (HIV+), compared with GBD DWs of 0.408 (HIV+) and 0.333 (HIV-) during active disease. Our results imply that the majority of TB-related morbidity occurs post-treatment .
Conclusion
TB-related DALYs are greatly underestimated by overlooking post-TB disability. The total disability burden of TB is likely undervalued by both GBD estimates and economic evaluations of interventions, particularly those aimed at early diagnosis and prevention.
Background
Two-thirds of children with tuberculosis have non-severe disease.
Method
SHINE was an open-label treatment-shortening non-inferiority trial in children with non-severe, symptomatic, presumed drug-susceptible, smear-negative tuberculosis, in Uganda, Zambia, South Africa and India. Children aged <16 years were randomised to 16- versus 24-week standard first-line anti-tuberculosis treatment using WHO-recommended paediatric fixed-dose-combinations and a non-inferiority margin of 6% was used. The primary efficacy outcome was a composite of treatment failure, anti-tuberculosis treatment changes/restarts, on-treatment loss-to-follow-up, TB recurrence or death by 72 weeks, excluding children not reaching 16 weeks follow-up (modified-intent-to-treat). Primary safety outcome was on-treatment grade ≥3 adverse events.
Results
1204 children (602 in each group) were enrolled between July 2016 and July 2018; median age 3.5 years (range 2 months-15 years), 52% male, 11% HIV-infected, 14% bacteriologically-confirmed tuberculosis. Retention by 72 weeks and adherence to allocated anti-tuberculosis treatment were 95% and 94%, respectively. Sixteen (3%) versus 18 (3%) children reached the primary efficacy outcome in 16- versus 24-week arms respectively: unadjusted difference -0.4%, 95% CI (-2.2, 1.5). Non-inferiority of 16-weeks was consistent across intention-to-treat, per-protocol and key secondary analyses including when restricting analysis to the 958 (80%) children independently adjudicated to have tuberculosis at baseline. 95 (8%) children experienced grade ≥3 adverse events, including 17 adverse reactions (11 hepatic, all except three occurred within first 8 weeks, when treatment arms were the same).
Conclusions
4-months anti-tuberculosis treatment was non-inferior to 6 months for children treated for drug-susceptible non-severe smear-negative tuberculosis.
(Supported by University College London; Trial Registration: ISRCTN 63579542)
Tuberculous meningitis disproportionately affects young children. As the most devastating form of tuberculosis, it is associated with unacceptably high rates of mortality and morbidity even if treated. Challenging to diagnose and treat, tuberculous meningitis commonly causes long-term neurodisability in those who do survive. There remains an urgent need for strengthened surveillance, improved rapid diagnostics technology, optimised anti-tuberculosis drug therapy, investigation of new host-directed therapy, and further research on long-term functional and neurodevelopmental outcomes to allow targeted intervention. This review focuses on the neglected field of paediatric tuberculous meningitis and bridges current clinical gaps with research questions to improve outcomes from this crippling disease.
Rationale
Pulmonary tuberculosis (PTB) can cause post-TB lung disease (PTLD) associated with respiratory symptoms, spirometric and radiological abnormalities. Understanding of the predictors and natural history of PTLD is limited.
Objectives
To describe the symptoms and lung function of Malawian adults up to 3 years following PTB-treatment completion, and to determine the evolution of PTLD over this period.
Methods
Adults successfully completing PTB treatment in Blantyre, Malawi were followed up for 3 years and assessed using questionnaires, post-bronchodilator spirometry, 6 min walk tests, chest X-ray and high-resolution CT. Predictors of lung function at 3 years were identified by mixed effects regression modelling.
Measurement and main results
We recruited 405 participants of whom 301 completed 3 years follow-up (mean (SD) age 35 years (10.2); 66.6% males; 60.4% HIV-positive). At 3 years, 59/301 (19.6%) reported respiratory symptoms and 76/272 (27.9%) had abnormal spirometry. The proportions with low FVC fell from 57/285 (20.0%) at TB treatment completion to 33/272 (12.1%), while obstruction increased from and 41/285 (14.4%) to 43/272 (15.8%) at 3 years. Absolute FEV 1 and FVC increased by mean 0.03 L and 0.1 L over this period, but FEV 1 decline of more than 0.1 L was seen in 73/246 (29.7%). Higher spirometry values at 3 years were associated with higher body mass index and HIV coinfection at TB-treatment completion.
Conclusion
Spirometric measures improved over the 3 years following treatment, mostly in the first year. However, a third of PTB survivors experienced ongoing respiratory symptoms and abnormal spirometry (with accelerated FEV 1 decline). Effective interventions are needed to improve the care of this group of patients.
The health needs of adolescents and young adults (AYAs) have been neglected in tuberculosis (TB) care, control, and research. AYAs, who are distinct from younger children and older adults, undergo dynamic physical, psychological, emotional, cognitive, and social development. Five domains of adolescent well-being are crucial to a successful transition between childhood and adulthood: (1) Good health; (2) connectedness and contribution to society; (3) safety and a supportive environment; (4) learning, competence, education, skills, and employability; and (5) agency and resilience. This review summarizes the evidence of the impact of TB disease and treatment on these five domains of AYA well-being.
Background
Many individuals who survive tuberculosis disease face ongoing disability and elevated mortality risks. However, the impact of post-tuberculosis sequelae is generally omitted from policy analyses and disease burden estimates. We therefore estimated the global burden of tuberculosis, inclusive of post-tuberculosis morbidity and mortality.
Methods
We constructed a hypothetical cohort of individuals developing tuberculosis in 2019, including pulmonary and extrapulmonary disease. We simulated lifetime health outcomes for this cohort, stratified by country, age, sex, HIV status, and treatment status. We used disability-adjusted life-years (DALYs) to summarise fatal and non-fatal health losses attributable to tuberculosis, during the disease episode and afterwards. We estimated post-tuberculosis mortality and morbidity based on the decreased lung function caused by pulmonary tuberculosis disease.
Findings
Globally, we estimated 122 (95% uncertainty interval [UI] 98–151) million DALYs due to incident tuberculosis disease in 2019, with 58 (38–83) million DALYs attributed to post-tuberculosis sequelae, representing 47% (95% UI 37–57) of the total burden estimate. The increase in burden from post-tuberculosis varied substantially across countries and regions, driven largely by differences in estimated case fatality for the disease episode. We estimated 12·1 DALYs (95% UI 10·0–14·9) per incident tuberculosis case, of which 6·3 DALYs (5·6–7·0) were from the disease episode and 5·8 DALYs (3·8–8·3) were from post-tuberculosis. Per-case post-tuberculosis burden estimates were greater for younger individuals, and in countries with high incidence rates. The burden of post-tuberculosis was spread over the remaining lifetime of tuberculosis survivors, with almost a third of total DALYs (28%, 95% UI 23–34) accruing 15 or more years after incident tuberculosis.
Interpretation
Post-tuberculosis sequelae add substantially to the overall disease burden caused by tuberculosis. This hitherto unquantified burden has been omitted from most previous policy analyses. Future policy analyses and burden estimates should take better account of post-tuberculosis, to avoid the potential misallocation of funding, political attention, and research effort resulting from continued neglect of this issue.
Funding
National Institutes of Health.
Background
Tuberculosis (TB) is among the top 10 causes of death worldwide and there are estimated 10.4 million new (incident) patients, of which about one fourth are in India. There has been calls for rigorous investigations and interventions that may address other factors known to have effect on adherence of treatment like Depression but the amount of research into comorbidity is surprisingly low. The aim of the study was to assess magnitude and impact of depression among TB patients and determine the treatment outcomes of TB in District Srinagar.
Methods
In this prospective study the adults with newly diagnosed TB were recruited within one month of initiating treatment and were followed upto the end of treatment. Data collection was done at three time-points: baseline, after 2 months and after 6 months of treatment initiation. The sample size of 200 was calculated using OpenEpi, V3 and identified 202 TB patients were interviewed in their local language and PHQ-9 scale was used to measure Depression.
Results
The prevalence of Depression at baseline was 50.5% with CI (43.7%-57.3%). After two months of treatment the prevalence reduced to 9.4% with CI (5.9%-14.0%) and at the end of treatment to 2.5% with CI (0.91%-5.4%). Association between Depression in TB patients and treatment failure was found to be small to medium as revealed by Cramer’s V test (0.29-0.59). Binary logistic regression estimated that at baseline TB patients with Depression were at 4.46 times at more risk of treatment failure than patients without Depression and those patients who continued Depression even after intensive phase were 34.5 times at higher risk.
Conclusion
Our findings indicate Depression is associated with poor treatment outcome in these patients, despite TB treatment. TB treatment strategies should consider screening and managing the psychologically distressed individuals among TB patients.
Background
There are few data on the on post-treatment experiences of people who have been successfully treated for rifampicin-resistant (RR-)TB.
Objective
To describe the experiences and impact of RR-TB disease and therapy on post-treatment life of individuals who were successfully treated.
Methods
In this qualitative study in-depth interviews were conducted among a purposively selected sample from a population of individuals who were successfully treated for RR-TB between January 2008 and December 2018. Interview transcripts and notes were analysed using a thematic network analysis which included grounded theory and a framework for understanding pathophysiological mechanisms for post-TB morbidity and mortality. The analysis was iterative and the coding system developed focused on disease, treatment and post-treatment experiences of individuals. This paper follows the COREQ guidelines.
Results
For all 12 participants interviewed, the development of RR-TB disease, its diagnosis and the subsequent treatment were a major disruption to their lives as well as a transformative experience. On diagnosis of RR-TB disease, participants entered a liminal period in which their lives were marked with uncertainty and dominated by physical and mental suffering. Irrespective of how long ago they had completed their treatment, they all remembered with clarity the signs and symptoms of the disease and the arduous treatment journey. Post-treatment participants reported physical, social, psychological and economic changes as consequences of their RR-TB disease and treatment. Many participants reported a diminished ability to perform physical activities and, once discharged from the RR-TB hospital, inadequate physical rehabilitation. For some, these physical limitations impacted on their social life, and ultimately on their psychological health as well as on their ability to earn money and support their families.
Conclusion
The experiences and impact of RR-TB disease and therapy on post-treatment life of individuals successfully treated, highlights gaps in the current health care system that need to be addressed to improve the life of individuals post-treatment. A more holistic and long-term view of post-TB health, including the provision of comprehensive medical and social services for post-treatment care of physical ailments, social re-integration and the mitigation of the perceived fear and risk of getting TB again could be a central part of person-centred TB care.
BACKGROUND: Post-TB lung disease (PTLD) is an important but under-recognised chronic respiratory disease in high TB burden settings such as Tanzania. METHODS: This was a cross-sectional survey of adults within 2 years of completion of TB treatment in Kilimanjaro, Tanzania. Data were collected using questionnaires (symptoms and exposures), spirometry and chest radiographs to assess outcome measures, which were correlated with daily life exposures, including environment and diet. RESULTS: Of the 219 participants enrolled (mean age: 45 years ± 10; 193 88% males), 98 (45%) reported chronic respiratory symptoms; 46 (22%) had received treatment for TB two or more times; and HIV prevalence was 35 (16%). Spirometric abnormalities were observed in 146 (67%). Chest X-ray abnormalities occurred in 177 (86%). A diagnosis of PTLD was made in 200 (91%), and half had clinically relevant PTLD. The prevalence of mMRC ≥Grade 3 chronic bronchitis and dyspnoea was respectively 11% and 26%. Older age, multiple episodes of TB and poverty indicators were linked with clinically relevant PTLD. CONCLUSIONS: We found a substantial burden of PTLD in adults who had recently completed TB treatment in Tanzania. There is a pressing need to identify effective approaches for both the prevention and management of this disease.
BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR). METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement). RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR. CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.
Background
The sustainable development goals aim to improve health for all by 2030. They incorporate ambitious goals regarding tuberculosis (TB), which may be a significant cause of disability, yet to be quantified. Therefore, we aimed to quantify the prevalence and types of TB-related disabilities.
Methods
We performed a systematic review of TB-related disabilities. The pooled prevalence of disabilities was calculated using the inverse variance heterogeneity model. The maps of the proportions of common types of disabilities by country income level were created.
Results
We included a total of 131 studies (217,475 patients) that were conducted in 49 countries. The most common type of disabilities were mental health disorders (23.1%), respiratory impairment (20.7%), musculoskeletal impairment (17.1%), hearing impairment (14.5%), visual impairment (9.8%), renal impairment (5.7%), and neurological impairment (1.6%). The prevalence of respiratory impairment (61.2%) and mental health disorders (42.0%) was highest in low-income countries while neurological impairment was highest in lower middle-income countries (25.6%). Drug-resistant TB was associated with respiratory (58.7%), neurological (37.2%), and hearing impairments (25.0%) and mental health disorders (26.0%), respectively.
Conclusions
TB-related disabilities were frequently reported. More uniform reporting tools for TB-related disability and further research to better quantify and mitigate it are urgently needed.
Prospero registration number
CRD42019147488
Background:
This is the first survey to use the World Health Organization (WHO) methodology to document the magnitude and main drivers of tuberculosis (TB) patient costs in order to guide policies on cost mitigation and to produce a baseline measure for the percentage of TB-affected households experiencing catastrophic costs in Myanmar.
Methods:
A nationally representative cross-sectional survey was administered to 1000 TB patients in health facilities from December 2015 to February 2016, focusing on costs of TB treatment (direct and indirect), household income, and coping strategies. A total cost was estimated for each household by extrapolating reported costs and comparing them to household income. If the proportion of total costs exceeded 20% of the annual household income, a TB-affected household was deemed to have faced catastrophic costs.
Results:
60% of TB-affected households faced catastrophic costs in Myanmar. On average, total costs were USD 759, and the largest proportion of this total was accounted for by patient time (USD 365), followed by food costs (USD 200), and medical expenses (USD 130). Low household wealth quintile and undergoing MDR-TB treatment were both significant predictors for households facing catastrophic costs.
Conclusions:
The high proportion of TB-affected households experiencing catastrophic costs suggests the need for TB-specific social protection programs in patient-centered healthcare. The survey findings have led the government and donors to increase support for MDR-TB patients. The significant proportion of total spending attributable to lost income and food or nutritional supplements suggests that income replacement programs and/or food packages may ameliorate the burdensome costs.
Background:
Post-tuberculosis (TB) lung disease is a recognised cause of chronic respiratory disease, and its impact on health-related quality of life (HRQoL) has not been extensively described.
Objectives:
To describe the clinical profile, spirometry impairment and impact of post-TB lung disease on HRQoL among patients attending two tertiary hospitals in Lagos, Nigeria.
Methods:
We conducted a cross-sectional study and obtained data through interviews, chart reviews and physical examination. We measured dyspnoea severity using the Medical Research Council (MRC) scale, HRQoL with the St George's respiratory questionnaire (SGRQ) and performed spirometry. Univariate regression was used to explore the associations between selected variables and HRQoL.
Results:
A total of 59 participants were recruited and their median (interquartile range (IQR)) age was 45 (36 - 60) years. The most frequent symptom was cough (93.2%; n=55) and sputum production (91.5%; n=54). Less than two-thirds of the participants (62.4%; n=38) had received treatment for TB on more than one occasion, 50.8% (n=30) had moderate to very severe dyspnoea on the MRC scale and 88.7% (n=47/53) had abnormal spirometry with the mixed pattern predominating in 56.6% (n=30) of the participants. The mean (standard deviation (SD)) SGRQ component score for symptoms was 43.89 (18.66), followed by activity (42.50 (22.68)), impact (29.41 (17.82)) and total components (35.78 (17.25)). Dyspnoea, cough, sputum production and weight loss were associated with worsened HRQoL.
Conclusion:
Post-TB lung disease was characterised by a high symptom burden, severe spirometry impairment and poor HRQoL. There is a need for increased recognition and development of guidelines for diagnosis and treatment of post-TB lung disease and for further studies to explore preventive strategies.
Background
Despite progress towards End TB Strategy targets for reducing tuberculosis (TB) incidence and deaths by 2035, South Africa remains among the top ten high-burden tuberculosis countries globally. A large challenge lies in how policies to improve detection, diagnosis and treatment completion interact with social and structural drivers of TB. Detailed understanding and theoretical development of the contextual determinants of problems in TB care is required for developing effective interventions. This article reports findings from the pre-implementation phase of a study of TB care in South Africa, contributing to He A lth S ystem S tr E ng T hening in Sub-Saharan Africa (ASSET)—a five-year research programme developing and evaluating health system strengthening interventions in sub-Saharan Africa. The study aimed to develop hypothetical propositions regarding contextual determinants of problems in TB care to inform intervention development to reduce TB deaths and incidence whilst ensuring the delivery of quality integrated, person-centred care.
Methods
Theory-building case study design using the Context and Implementation of Complex Interventions (CICI) framework to identify contextual determinants of problems in TB care. Between February and November 2019, we used mixed methods in six public-sector primary healthcare facilities and one public-sector hospital serving impoverished urban and rural communities in the Amajuba District of KwaZulu-Natal Province, South Africa. Qualitative data included stakeholder interviews, observations and documentary analysis. Quantitative data included routine data on sputum testing and TB deaths. Data were inductively analysed and mapped onto the seven CICI contextual domains.
Results
Delayed diagnosis was caused by interactions between fragmented healthcare provision; limited resources; verticalised care; poor TB screening, sputum collection and record-keeping. One nurse responsible for TB care, with limited integration of TB with other conditions, and policy focused on treatment adherence contributed to staff stress and limited consideration of patients’ psychosocial needs. Patients were lost to follow up due to discontinuity of information, poverty, employment restrictions and limited support for treatment side-effects. Infection control measures appeared to be compromised by efforts to integrate care.
Conclusions
Delayed diagnosis, limited psychosocial support for patients and staff, patients lost to follow-up and inadequate infection control are caused by an interaction between multiple interacting contextual determinants. TB policy needs to resolve tensions between treating TB as epidemic and individually-experienced social problem, supporting interventions which strengthen case detection, infection control and treatment, and also promote person-centred support for healthcare professionals and patients.
Graphic abstract
The British Thoracic Society (BTS) launched a Global Health Group in the winter of 2019 in partnership with the Pan African Thoracic Society. This key meeting generated a lot of interest and areas of mutual benefit. Due to the overwhelming interest at the 2019 meeting, a virtual offering of the BTS Winter meeting February 2021, included a symposium by the Global Health Group on Africa’s Respiratory “Big Five.” The Winter meeting was free for PATS members and symposium had an excellent attendance, covering the following areas: Pneumonia in the under 5, impact of air pollution on lung health, post-TB lung disease, and non-communicable respiratory disease across the life course. This paper is a summary of the symposium and seeks to address research priority areas for lung health research on the African continent.
Introduction
Depression and anxiety among tuberculosis (TB) patients can adversely affect TB treatment adherence and completion.
Aim
We studied whether integrating mental health services into existing TB treatment programs would reduce symptoms of depression and anxiety and improve treatment completion among patients with drug-susceptible TB.
Methods
Integrated practice units (IPUs) for TB and mental health were established within six existing TB treatment facilities in Karachi, Pakistan. Patients were screened for depression and anxiety and, if symptomatic, offered a mental health intervention consisting of at least four counseling sessions. We measured changes in reported levels of depression and anxiety symptoms from baseline following completion of counseling sessions, and rates of TB treatment completion.
Results
Between February 2017 and June 2018, 3500 TB patients were screened for depression and anxiety. 1057 (30.2%) symptomatic patients received a baseline adherence session. 1012 enrolled for a mental health intervention received at least 1 counseling session. 522 (51.5%) reported no symptoms after four to six sessions. Symptomatic patients who completed at least four counseling sessions had higher rates of TB treatment completion than those who did not (92.9% vs 75.1%; p < 0.0001).
Conclusion
Mental health interventions integrated within TB programs can help reduce symptoms of depression and anxiety and improve TB treatment completion.
We aimed to review the literature on interventions for treating Common Mental Disorders (CMD) in people with Tuberculosis (TB). We followed PRISMA guidelines and the protocol was registered at PROSPERO. The electronic databases (PsycInfo, CINAHL, Medline, Google Scholar, Embase) were searched from 1982 to 2020. 349 relevant records were screened, with 26 examined at full text. 13 studies were included totalling 4326 participants. A meta-analysis was not possible due to nature of data, thus descriptive synthesis was conducted. Eleven studies evaluated psychosocial interventions, which significantly improved adherence or cure rates from TB, anxiety and depression. The elements of effective psychosocial interventions included; combating stigma, socioeconomic disadvantage, managing associated guilt and fear of contagion, and explanatory models of illness in local population. Two articles evaluated pharmacological interventions (antidepressants and Vitamin D). This is the first systematic review of interventions to treat CMD in TB. The studies were mostly low quality and mental health outcomes were not adequately described. However, this review suggests that it is feasible to develop and test interventions for improving mental health outcomes and enhancing treatment adherence in TB.
BACKGROUND
Persistent respiratory symptoms and lung function deficits are common after patients with TB. We aimed to define the burden of post-TB lung disease (PTLD) and assess associations between symptoms and impairment in two high TB incidence communities.
METHODS
This was a cross-sectional survey of adults in Cape Town, South Africa who completed TB treatment 1–5 years previously. Questionnaires, spirometry and 6-minute walking distance (6MWD) were used to assess relationships between outcome measures and associated factors.
RESULTS
Of the 145 participants recruited (mean age: 42 years, range: 18–75; 55 [38%] women), 55 (38%) had airflow obstruction and 84 (58%) had low forced vital capacity (FVC); the mean 6MWD was 463 m (range: 240–723). Respiratory symptoms were common: chronic cough (n = 27, 19%), wheeze (n = 61, 42%) and dyspnoea (modified MRC dyspnoea score 3 or 4: n = 36, 25%). There was poor correlation between FVC or obstruction and 6MWD. Only low body mass index showed consistent association with outcomes on multivariable analyses. Only 19 (13%) participants had a diagnosis of respiratory disease, and 16 (11%) currently received inhalers.
CONCLUSION
There was substantial burden of symptoms and physiological impairment in this “cured” population, but poor correlation between objective outcome measures, highlighting deficits in our understanding of PTLD.
The WHO developed a generic ‘TB patient cost survey’ tool and a standardized approach to assess the direct and indirect costs of TB incurred by patients and their households, estimate the proportion of patients experiencing catastrophic costs, and measure the impact of interventions to reduce patient costs. While the generic tool is a facility-based cross-sectional survey, this standardized approach needs to be adapted for longitudinal studies. A longitudinal approach may overcome some of the limitations of a cross-sectional design and estimate the economic burden of TB more precisely. We describe the process of creating a longitudinal instrument and its application to the TB Sequel study, an ongoing multi-country, multi-center observational cohort study. We adapted the cross-sectional WHO generic TB patient cost survey instrument for the longitudinal study design of TB Sequel and the local context in each study country (South Africa, Mozambique, Tanzania, and The Gambia). The generic instrument was adapted for use at enrollment (start of TB treatment; Day 0) and at 2, 6, 12 and 24 months after enrollment, time points intended to capture costs incurred for diagnosis, during treatment, at the end of treatment, and during long-term follow-up once treatment has been completed. These time points make the adapted version suitable for use in patients with either drug-sensitive or drug-resistant TB. Using the adapted tool provides the opportunity to repeat measures and make comparisons over time, describe changes that extend beyond treatment completion, and link cost survey data to treatment outcomes and post-TB sequelae.
Trial registration: ClinicalTrials.gov: NCT032516 August 1196, 2017.
Abbreviations: DOTS: Directly observed treatment, short-course; DR-TB: Drug-resistant tuberculosis; MDR-TB: Multi-drug resistant tuberculosis; NTP: National Tuberculosis Programme; TB: Tuberculosis; USD: United States Dollar; WHO: World Health Organization.
An estimated 58 million people have survived tuberculosis since 2000, yet many of them will suffer from post-tuberculosis lung disease (PTLD). PTLD results from a complex interplay between organism, host, and environmental factors and affects long-term respiratory health. PTLD is an overlapping spectrum of disorders that affects large and small airways (bronchiectasis and obstructive lung disease), lung parenchyma, pulmonary vasculature, and pleura and may be complicated by co-infection and haemoptysis. People affected by PTLD have shortened life expectancy and increased risk of recurrent tuberculosis, but predictors of long-term outcomes are not known. No data are available on PTLD in children and on impact throughout the life course. Risk-factors for PTLD include multiple episodes of tuberculosis, drug-resistant tuberculosis, delays in diagnosis, and possibly smoking. Due to a lack of controlled trials in this population, no evidence-based recommendations for the investigation and management of PTLD are currently available. Empirical expert opinion advocates pulmonary rehabilitation, smoking cessation, and vaccinations (pneumococcal and influenza). Exacerbations in PTLD remain both poorly understood and under-recognised. Among people with PTLD, the probability of tuberculosis recurrence must be balanced against other causes of symptom worsening. Unnecessary courses of repeated empiric anti-tuberculosis chemotherapy should be avoided. PTLD is an important contributor to the global burden of chronic lung disease. Advocacy is needed to increase recognition for PTLD and its associated economic, social, and psychological consequences and to better understand how PTLD sequelae could be mitigated. Research is urgently needed to inform policy to guide clinical decision-making and preventative strategies for PTLD.
Background:
The stigma of tuberculosis (TB) poses a significant challenge to TB control because it leads to delayed diagnosis and non-adherence. However, few studies on TB-related stigma have been completed in China. The aim of the current study was to explore the status of TB-related stigma and its associated predictive factors among TB patients in Dalian, Northeast China.
Methods:
An institution-based, cross-sectional survey was conducted among outpatients at Dalian Tuberculosis Hospital in Liaoning Province, Northeast China. Data were collected by using a questionnaire that measured TB-related stigma, treatment status, anxiety, social support, doctor-patient communication and so on. A multiple linear regression model was used to determine the predictors of TB-related stigma.
Results:
A total of 601 eligible participants were recruited. The mean score for TB-related stigma was 9.07, and the median score was 10. The average scores for anxiety, social support and doctor-patient communication were 4.03, 25.41 and 17.17, respectively. Multiple linear regression analysis revealed that patients who were female (β = 1.19, 95% CI: 0.38-2.01, P < 0.05), had self-assessed moderate or severe disease (β = 1.08, 95% CI: 0.12-2.03 and β = 1.36, 95% CI: 0.03-2.70, respectively, P < 0.05), and had anxiety (β = 0.38, 95% CI: 0.30-0.46, P < 0.001) were more likely to have a greater level of TB-related stigma than their counterparts. However, a significantly lower level of TB-related stigma was observed in patients with good social support (β = - 0.25, 95% CI: - 0.33--0.17, P < 0.001) and doctor-patient communication (β = - 0.14, 95% CI: - 0.29--0.00, P < 0.05).
Conclusions:
This study showed that stigma among TB patients was high. Targeted attention should be paid to female patients and patients with moderate or severe disease in TB stigma-related interventions. Moreover, the important role of social support and doctor-patient communication in reducing TB-related stigma should also be emphasized.
Background
Mitigating the socioeconomic impact of tuberculosis (TB) is key to the WHO End TB Strategy. However, little known about socioeconomic well-being beyond TB-treatment completion. In this mixed-methods study, we describe socioeconomic outcomes after TB-disease in urban Blantyre, Malawi, and explore pathways and barriers to financial recovery.
Methods
Adults ≥15 years successfully completing treatment for a first episode of pulmonary TB under the National TB Control Programme were prospectively followed up for 12 months. Socioeconomic, income, occupation, health seeking and cost data were collected. Determinants and impacts of ongoing financial hardship were explored through illness narrative interviews with purposively selected participants.
Results
405 participants were recruited from February 2016 to April 2017. Median age was 35 years (IQR: 28–41), 67.9% (275/405) were male, and 60.6% (244/405) were HIV-positive. Employment and incomes were lowest at TB-treatment completion, with limited recovery in the following year: fewer people were in paid work (63.0% (232/368) vs 72.4% (293/405), p=0.006), median incomes were lower (US0–US72.20 (IQR: US26.71–US173.29), p<0.001), and more patients were living in poverty (earning <US$1.90/day: 57.7% (211/366) vs 41.6% (166/399), p<0.001) 1 year after TB-treatment completion compared with before TB-disease onset. Half of the participants (50.5%, 184/368) reported ongoing dissaving (use of savings, selling assets, borrowing money) and 9.5% (35/368) reported school interruptions in the year after TB-treatment completion. Twenty-one participants completed in-depth interviews. Reported barriers to economic recovery included financial insecurity, challenges rebuilding business relationships, residual physical morbidity and stigma.
Conclusions
TB-affected households remain economically vulnerable even after TB-treatment completion, with limited recovery in income and employment, persistent financial strain requiring dissaving, and ongoing school interruptions. Measures of the economic impact of TB disease should include the post-TB period. Interventions to protect the long-term health and livelihoods of TB survivors must be explored.
A dysregulated host immune response significantly contributes to morbidity and mortality in tuberculous meningitis (TBM). Effective host directed therapies (HDTs) are critical to improve survival and clinical outcomes. Currently only one HDT, dexamethasone, is proven to improve mortality. However, there is no evidence dexamethasone reduces morbidity, how it reduces mortality is uncertain, and it has no proven benefit in HIV co-infected individuals. Further research on these aspects of its use, as well as alternative HDTs such as aspirin, thalidomide and other immunomodulatory drugs is needed. Based on new knowledge from pathogenesis studies, repurposed therapeutics which act upon small molecule drug targets may also have a role in TBM. Here we review existing literature investigating HDTs in TBM, and propose new rationale for the use of novel and repurposed drugs. We also discuss host variable responses and evidence to support a personalised approach to HDTs in TBM.
Neuroradiological abnormalities in tuberculous meningitis (TBM) are common, but the exact relationship with clinical and inflammatory markers has not been well established. We performed magnetic resonance imaging (MRI) at baseline and after two months treatment to characterise neuroradiological patterns in a prospective cohort of adult TBM patients in Indonesia. We included 48 TBM patients (median age 30, 52% female, 8% HIV-infected), most of whom had grade II (90%), bacteriologically confirmed (71%) disease, without antituberculotic resistance. Most patients had more than one brain lesion (83%); baseline MRIs showed meningeal enhancement (89%), tuberculomas (77%), brain infarction (60%) and hydrocephalus (56%). We also performed an exploratory analysis associating MRI findings to clinical parameters, response to treatment, paradoxical reactions and survival. The presence of multiple brain lesion was associated with a lower Glasgow Coma Scale and more pronounced motor, lung, and CSF abnormalities (p-value <0.05). After two months, 33/37 patients (89%) showed worsening of MRI findings, mostly consisting of new or enlarged tuberculomas. Baseline and follow-up MRI findings and paradoxical responses showed no association with six-month mortality. Severe TBM is characterized by extensive MRI abnormalities at baseline, and frequent radiological worsening during treatment.
Background
Despite the high burden of disease in younger children there are few tools specifically designed to estimate Health Related Quality of Life (HRQoL) in children younger than 3 years of age. A previous paper described the process of identifying a pool of items which might be suitable for measuring HRQoL of children aged 0–3 years. The current paper describes how the items were pruned and the final draft of the measure, Toddler and Infant (TANDI) Health Related Quality of Life, was tested for validity and reliability.
Methods
A sample of 187 caregivers of children 1–36 months of age were recruited which included children who were either acutely ill (AI), chronically ill (CI) or from the general school going population (GP). The TANDI, an experimental version of the EQ-5D-Y proxy, included six dimensions with three levels of report and general health measured on a Visual Analogue Scale (VAS) from 0 to 100. The content validity had been established during the development of the instrument. The TANDI, Ages and Stages Questionnaire (ASQ), Faces, Leg, Activity, Cry, Consolabilty (FLACC) or Neonatal Infant Pain Scale (NIPS) and a self-designed dietary information questionnaire were administered at baseline. The TANDI was administered 1 week later in GP children to establish test-retest reliability. The distribution of dimension scores, Cronbach’s alpha, rotated varimax factor analysis, Spearman’s Rho Correlation, the intraclass correlation coefficient, Pearson’s correlation, analysis of variance and regression analysis were used to explore the reliability, and validity of the TANDI.
Results
Concurrent validity of the different dimensions was tested between the TANDI and other instruments. The Spearman’s Rho coefficients were significant and moderate to strong for dimensions of activity and participation and significant and weak for items of body functions. Known groups were compared and children with acute illness had the lowest ranked VAS (median 60, range 0–100), indicating worse HRQoL. The six dimensions of the TANDI were tested for internal consistency and reliability and the Cronbach’s α as 0.83. Test-retest results showed no variance for dimension scores of movement and play, and high agreement for pain (83%), relationships (87%), communication (83%) and eating (74%). The scores were highly correlated for the VAS (ICC = 0.76; p < 0.001).
Conclusion
The TANDI was found to be valid and reliable for use with children aged 1–36 months in South Africa. It is recommended that the TANDI be included in future research to further investigate HRQoL and the impact of interventions in this vulnerable age group. It is further recommended that future testing be done to assess the feasibility, clinical utility, and cross-cultural validity of the measure and to include international input in further development.
Background
Tuberculosis (TB) patients incur large costs for care seeking, diagnosis, and treatment. To understand the magnitude of this financial burden and its main cost drivers, the Lao People’s Democratic Republic (PDR) National TB Programme carried out the first national TB patient cost survey in 2018–2019.
Method
A facility-based cross-sectional survey was conducted based on a nationally representative sample of TB patients from public health facilities across 12 provinces. A total of 848 TB patients including 30 drug resistant (DR)-TB and 123 TB-HIV coinfected patients were interviewed using a standardised questionnaire developed by the World Health Organization. Information on direct medical, direct non-medical and indirect costs, as well as coping mechanisms was collected. We estimated the percentage of TB-affected households facing catastrophic costs, which was defined as total TB-related costs accounting for more than 20% of annual household income.
Result
The median total cost of TB care was US$ 755 (Interquartile range 351–1,454). The costs were driven by direct non-medical costs (46.6%) and income loss (37.6%). Nutritional supplements accounted for 74.7% of direct non-medical costs. Half of the patients used savings, borrowed money or sold household assets to cope with TB. The proportion of unemployment more than doubled from 16.8% to 35.4% during the TB episode, especially among those working in the informal sector. Of all participants, 62.6% of TB-affected households faced catastrophic costs. This proportion was higher among households with DR-TB (86.7%) and TB-HIV coinfected patients (81.1%).
Conclusion
In Lao PDR, TB patients and their households faced a substantial financial burden due to TB, despite the availability of free TB services in public health facilities. As direct non-medical and indirect costs were major cost drivers, providing free TB services is not enough to ease this financial burden. Expansion of existing social protection schemes to accommodate the needs of TB patients is necessary.
Purpose
Tuberculosis (TB) can affect sleep and can predispose patients to chronic diseases like diabetes mellitus. On the other hand, sleep deprivation and diabetes mellitus can worsen tuberculosis. The aim of this study was to assess sleep quality, to estimate the prevalence of poor sleepers and those at risk for restless legs syndrome (RLS) and to evaluate the knowledge and practices regarding sleep hygiene among patients diagnosed with TB.
Methods
In a cross-sectional study, a semi-structured questionnaire was administered to patients diagnosed with TB in Bengaluru, India. The questionnaire was comprised of sections including demography, knowledge and practice regarding sleep hygiene, the international restless leg study group consensus diagnostic criteria to diagnose RLS, the Pittsburgh sleep quality index, the Epworth sleepiness scale, and history of adverse drug reactions (ADRs).
Results
Of 206 participants enrolled, 125 men (61%), mean (SD) age was 41.0 (16.2) years, and 121 (59%) had pulmonary TB while the remaining 85 (41%) had extrapulmonary TB. The prevalence (95% confidence intervals) of poor quality sleepers was 17% (12, 23%), those with poor knowledge of sleep hygiene (< 6 marks) 33% (27, 40%), those at risk for RLS 32% (26, 39%), and those with excessive daytime sleepiness (EDS) 12% (8, 17%).
Conclusion
Prevalence of poor quality sleepers and those at risk for RLS are higher than normal population, thus making sleep quality assessment important in patients diagnosed with TB. Prevalence of those at risk for EDS was comparable to normal population.
Background
People successfully completing treatment for tuberculosis remain at elevated risk for recurrent disease, either from relapse or reinfection. Identifying risk factors for recurrent tuberculosis may help target post-tuberculosis screening and care.
Methods
We enrolled 500 patients with smear-positive pulmonary tuberculosis in South Africa and collected baseline data on demographics, clinical presentation and sputum mycobacterial cultures for 24-loci mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing. We used routinely-collected administrative data to identify recurrent episodes of tuberculosis occurring over a median of six years after successful treatment completion.
Results
Of 500 patients initially enrolled, 333 (79%) successfully completed treatment for tuberculosis. During the follow-up period 35 patients with successful treatment (11%) experienced a bacteriologically confirmed tuberculosis recurrence. In our Cox proportional hazards model, a 3+ AFB sputum smear grade was significantly associated with recurrent tuberculosis with a hazard ratio of 3.33 (95% CI 1.44–7.7). The presence of polyclonal M. tuberculosis infection at baseline had a hazard ratio for recurrence of 1.96 (95% CI 0.86–4.48).
Conclusion
Our results indicate that AFB smear grade is independently associated with tuberculosis recurrence after successful treatment for an initial episode while the association between polyclonal M. tuberculosis infection and increased risk of recurrence appears possible.
Background:
Tuberculosis (TB) patients in Uganda incur large costs related to the illness, and while seeking and receiving health care. Such costs create access and adherence barriers which affect health outcomes and increase transmission of disease. The study ascertained the proportion of Ugandan TB affected households incurring catastrophic costs and the main cost drivers.
Methods:
A cross-sectional survey with retrospective data collection and projections was conducted in 2017. A total of 1178 drug resistant (DR) TB (44) and drug sensitive (DS) TB patients (1134), 2 weeks into intensive or continuation phase of treatment were consecutively enrolled across 67 randomly selected TB treatment facilities.
Results:
Of the 1178 respondents, 62.7% were male, 44.7% were aged 15-34 years and 55.5% were HIV positive. For each TB episode, patients on average incurred costs of USD 396 for a DS-TB episode and USD 3722 for a Multi drug resistant tuberculosis (MDR TB) episode. Up to 48.5% of households borrowed, used savings or sold assets to defray these costs. More than half (53.1%) of TB affected households experienced TB-related costs above 20% of their annual household expenditure, with the main cost drivers being non-medical expenditure such as travel, nutritional supplements and food.
Conclusion:
Despite free health care in public health facilities, over half of Ugandan TB affected households experience catastrophic costs. Roll out of social protection interventions like TB assistance programs, insurance schemes, and enforcement of legislation related to social protection through multi-sectoral action plans with central NTP involvement would palliate these costs.
Introduction
The emerging epidemiological evidence of increased cardiovascular disease (CVD) risk among persons diagnosed with tuberculosis (TB) has not been systematically reviewed to date. Our aim was to review the existing epidemiological evidence for elevated risk of CVD morbidity and mortality among persons diagnosed with TB compared to controls.
Materials and methods
EMBASE, MEDLINE, and Cochrane databases were searched (inception to January 2020) for terms related to “tuberculosis” and “cardiovascular diseases”. Inclusion criteria: trial, cohort, or case-control study design; patient population included persons diagnosed with TB infection or disease; relative risk (RR) estimate and confidence interval reported for CVD morbidity or mortality compared to suitable controls. Exclusion criteria: no TB or CVD outcome definition; duplicate study; non-English abstract; non-human participants. Two reviewers screened studies, applied ROBINS-I tool to assess risk of bias, and extracted data independently. Random effects meta-analysis estimated a pooled RR of CVD morbidity and mortality for persons diagnosed with TB compared to controls.
Results
6,042 articles were identified, 244 full texts were reviewed, and 16 were included, meta-analyzing subsets of 8 studies’ RR estimates. We estimated a pooled RR of 1.51 (95% CI: 1.16–1.97) for major adverse cardiac events among those diagnosed with TB compared to non-TB controls (p = 0.0024). A ‘serious’ pooled risk of bias was found across studies with between-study heterogeneity (I2 = 75.3%).
Conclusions
TB appears to be a marker for increased CVD risk; however, the literature is limited and is accompanied by serious risk of confounding bias and evidence of publication bias. Further retrospective and prospective studies are needed. Pending this evidence, best practice may be to consider persons diagnosed with TB at higher risk of CVD as a precautionary measure.
Background
There is substantial variation in the reported treatment outcomes for adult tuberculous meningitis (TBM). Data on survival and neurological disability by continent and HIV serostatus are scarce.
Methods
We performed a systematic review and meta-analysis to characterize treatment outcomes for adult TBM. Following a systematic literature search (MEDLINE and EMBASE), studies underwent duplicate screening by independent reviewers in two stages to assess eligibility for inclusion. Two independent reviewers extracted data from included studies. We employed a random effects model for all meta-analyses. We evaluated heterogeneity by the I2 statistic.
Results
We assessed 2,197 records for eligibility; 39 primary research articles met our inclusion criteria reporting on treatment outcomes for 5,752 adults with TBM. The commonest reported outcome measure was six-month mortality. Pooled six-month mortality was 24% and showed significant heterogeneity (I2 >95%; p<0·01). Mortality ranged from 2% to 67% in Asian studies and from 23% to 80% in sub-Saharan African studies. Mortality was significantly worse in HIV-positive adults at 57% (95%CI; 48-67%), compared with 16% (95%CI; 10-24%) in HIV-negative adults (p<0·01). Physical disability was reported in 32% (95%CI; 22-43%) of adult TBM survivors. There was considerable heterogeneity between studies in all meta-analyses with I2 statistics consistently >50%.
Conclusions
Mortality in adult TBM is high and varies considerably by continent and HIV-status. The highest mortality is amongst HIV-positive adults in sub-Saharan Africa. Standardized reporting of treatment outcomes will be essential to improve future data quality and increase potential for data sharing, meta-analyses, and facilitating multi-center tuberculosis research to improve outcomes.
Studies on using inhaled corticosteroids (ICS) and the risk of nontuberculous mycobacterial lung disease (NTM-LD) are limited and have some conflict results. We recruited 1,235 NTM-LD patients and found that the ICS use within 1 year was associated with increased NTM-LD, and the risk increased by elevating ICS dose and cumulative duration. Discontinuation of ICS use for more than 120 days could reduce the risk of NTM-LD to an insignificant level. For NTM species, the development of NTM-LD by ICS was highest for M. kansasii lung disease. The pooled results of the meta-analysis echoed that ICS use might increase risk of NTM-LD with dose response since medium daily ICS dose. In addition, budesonide had a smaller impact on the risk of NTM-LD than other ICS medications. The present study and meta-analysis provided evidence for ICS adjustment including dose, discontinuation effect and medications to possibly reduce the risk of NTM-LD.
Objective
Many important risk factors are associated with tuberculosis (TB) recurrence; among them, smoking is the most common and modifiable behavioural factor. We aimed to assess the association of smoking status and cessation support during anti-TB treatment with subsequent TB recurrence.
Method
A 7-year prospective cohort study was performed on 634 TB patients in China. The participants were grouped by smoking status at baseline. Cox proportional hazards models were applied to analyse the association between baseline characteristics and TB recurrence. The cumulative incidence of TB recurrence was estimated by Kaplan-Meier curves.
Results
Multivariable analysis showed that patients who continued smoking during anti-TB treatment were at higher risk for TB recurrence (HR= 3.45; 95% CI: 1.54–7.73) than nonsmokers. Moreover, this risk remained significant even in those who stopped smoking during anti-TB treatment (HR = 2.75; 95% CI: 1.47–5.14) than nonsmokers. The association between smoking and TB recurrence was stronger for smear-positive TB patients than for smear-negative TB patients. Among all the subgroups, patients who continued smoking had a higher TB recurrence rate over the 7-year follow-up than those who successfully quit during their anti-TB treatment (log-rank statistic, P< 0.01). With the increase in the number of cigarettes smoked daily, the TB recurrence risk also increased accordingly (log-rank statistic, P= 0.02).
Conclusion
Our findings highlight the importance of incorporating effective smoking cessation intervention measures into TB services and call for continuous monitoring of TB recurrence. Among patients who continue smoking or have a history of smoking, special attention should be given to smear-positive patients and heavy smokers when monitoring recurrence.
Low-income and middle-income countries (LMICs) bear a disproportionately high burden of the global morbidity and mortality caused by chronic respiratory diseases (CRDs), including asthma, chronic obstructive pulmonary disease, bronchiectasis, and post-tuberculosis lung disease. CRDs are strongly associated with poverty, infectious diseases, and other non-communicable diseases (NCDs), and contribute to complex multi-morbidity, with major consequences for the lives and livelihoods of those affected. The relevance of CRDs to health and socioeconomic wellbeing is expected to increase in the decades ahead, as life expectancies rise and the competing risks of early childhood mortality and infectious diseases plateau. As such, the World Health Organization has identified the prevention and control of NCDs as an urgent development issue and essential to the achievement of the Sustainable Development Goals by 2030. In this Review, we focus on CRDs in LMICs. We discuss the early life origins of CRDs; challenges in their prevention, diagnosis, and management in LMICs; and pathways to solutions to achieve true universal health coverage.
Background:
Xpert MTB/RIF and Xpert MTB/RIF Ultra (Xpert Ultra) are World Health Organization (WHO)-recommended rapid tests that simultaneously detect tuberculosis and rifampicin resistance in people with signs and symptoms of tuberculosis. This review builds on our recent extensive Cochrane Review of Xpert MTB/RIF accuracy.
Objectives:
To compare the diagnostic accuracy of Xpert Ultra and Xpert MTB/RIF for the detection of pulmonary tuberculosis and detection of rifampicin resistance in adults with presumptive pulmonary tuberculosis. For pulmonary tuberculosis and rifampicin resistance, we also investigated potential sources of heterogeneity. We also summarized the frequency of Xpert Ultra trace-positive results, and estimated the accuracy of Xpert Ultra after repeat testing in those with trace-positive results.
Search methods:
We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, Web of Science, LILACS, Scopus, the WHO ICTRP, the ISRCTN registry, and ProQuest to 28 January 2020 with no language restriction.
Selection criteria:
We included diagnostic accuracy studies using respiratory specimens in adults with presumptive pulmonary tuberculosis that directly compared the index tests. For pulmonary tuberculosis detection, the reference standards were culture and a composite reference standard. For rifampicin resistance, the reference standards were culture-based drug susceptibility testing and line probe assays.
Data collection and analysis:
Two review authors independently extracted data using a standardized form, including data by smear and HIV status. We assessed risk of bias using QUADAS-2 and QUADAS-C. We performed meta-analyses comparing pooled sensitivities and specificities, separately for pulmonary tuberculosis detection and rifampicin resistance detection, and separately by reference standard. Most analyses used a bivariate random-effects model. For tuberculosis detection, we estimated accuracy in studies in participants who were not selected based on prior microscopy testing or history of tuberculosis. We performed subgroup analyses by smear status, HIV status, and history of tuberculosis. We summarized Xpert Ultra trace results.
Main results:
We identified nine studies (3500 participants): seven had unselected participants (2834 participants). All compared Xpert Ultra and Xpert MTB/RIF for pulmonary tuberculosis detection; seven studies used a paired comparative accuracy design, and two studies used a randomized design. Five studies compared Xpert Ultra and Xpert MTB/RIF for rifampicin resistance detection; four studies used a paired design, and one study used a randomized design. Of the nine included studies, seven (78%) were mainly or exclusively in high tuberculosis burden countries. For pulmonary tuberculosis detection, most studies had low risk of bias in all domains. Pulmonary tuberculosis detection Xpert Ultra pooled sensitivity and specificity (95% credible interval) against culture were 90.9% (86.2 to 94.7) and 95.6% (93.0 to 97.4) (7 studies, 2834 participants; high-certainty evidence) versus Xpert MTB/RIF pooled sensitivity and specificity of 84.7% (78.6 to 89.9) and 98.4% (97.0 to 99.3) (7 studies, 2835 participants; high-certainty evidence). The difference in the accuracy of Xpert Ultra minus Xpert MTB/RIF was estimated at 6.3% (0.1 to 12.8) for sensitivity and -2.7% (-5.7 to -0.5) for specificity. If the point estimates for Xpert Ultra and Xpert MTB/RIF are applied to a hypothetical cohort of 1000 patients, where 10% of those presenting with symptoms have pulmonary tuberculosis, Xpert Ultra will miss 9 cases, and Xpert MTB/RIF will miss 15 cases. The number of people wrongly diagnosed with pulmonary tuberculosis would be 40 with Xpert Ultra and 14 with Xpert MTB/RIF. In smear-negative, culture-positive participants, pooled sensitivity was 77.5% (67.6 to 85.6) for Xpert Ultra versus 60.6% (48.4 to 71.7) for Xpert MTB/RIF; pooled specificity was 95.8% (92.9 to 97.7) for Xpert Ultra versus 98.8% (97.7 to 99.5) for Xpert MTB/RIF (6 studies). In people living with HIV, pooled sensitivity was 87.6% (75.4 to 94.1) for Xpert Ultra versus 74.9% (58.7 to 86.2) for Xpert MTB/RIF; pooled specificity was 92.8% (82.3 to 97.0) for Xpert Ultra versus 99.7% (98.6 to 100.0) for Xpert MTB/RIF (3 studies). In participants with a history of tuberculosis, pooled sensitivity was 84.2% (72.5 to 91.7) for Xpert Ultra versus 81.8% (68.7 to 90.0) for Xpert MTB/RIF; pooled specificity was 88.2% (70.5 to 96.6) for Xpert Ultra versus 97.4% (91.7 to 99.5) for Xpert MTB/RIF (4 studies). The proportion of Ultra trace-positive results ranged from 3.0% to 30.4%. Data were insufficient to estimate the accuracy of Xpert Ultra repeat testing in individuals with initial trace-positive results. Rifampicin resistance detection Pooled sensitivity and specificity were 94.9% (88.9 to 97.9) and 99.1% (97.7 to 99.8) (5 studies, 921 participants; high-certainty evidence) for Xpert Ultra versus 95.3% (90.0 to 98.1) and 98.8% (97.2 to 99.6) (5 studies, 930 participants; high-certainty evidence) for Xpert MTB/RIF. The difference in the accuracy of Xpert Ultra minus Xpert MTB/RIF was estimated at -0.3% (-6.9 to 5.7) for sensitivity and 0.3% (-1.2 to 2.0) for specificity. If the point estimates for Xpert Ultra and Xpert MTB/RIF are applied to a hypothetical cohort of 1000 patients, where 10% of those presenting with symptoms have rifampicin resistance, Xpert Ultra will miss 5 cases, and Xpert MTB/RIF will miss 5 cases. The number of people wrongly diagnosed with rifampicin resistance would be 8 with Xpert Ultra and 11 with Xpert MTB/RIF. We identified a higher number of rifampicin resistance indeterminate results with Xpert Ultra, pooled proportion 7.6% (2.4 to 21.0) compared to Xpert MTB/RIF pooled proportion 0.8% (0.2 to 2.4). The estimated difference in the pooled proportion of indeterminate rifampicin resistance results for Xpert Ultra versus Xpert MTB/RIF was 6.7% (1.4 to 20.1).
Authors' conclusions:
Xpert Ultra has higher sensitivity and lower specificity than Xpert MTB/RIF for pulmonary tuberculosis, especially in smear-negative participants and people living with HIV. Xpert Ultra specificity was lower than that of Xpert MTB/RIF in participants with a history of tuberculosis. The sensitivity and specificity trade-off would be expected to vary by setting. For detection of rifampicin resistance, Xpert Ultra and Xpert MTB/RIF had similar sensitivity and specificity. Ultra trace-positive results were common. Xpert Ultra and Xpert MTB/RIF provide accurate results and can allow rapid initiation of treatment for rifampicin-resistant and multidrug-resistant tuberculosis.
There is increasing awareness of bronchiectasis in children and adolescents, a chronic pulmonary disorder associated with poor quality-of-life for the child/adolescent and their parents, recurrent exacerbations and costs to the family and health systems. Optimal treatment improves clinical outcomes. Several national guidelines exist, but there are no international guidelines.
The European Respiratory Society (ERS) Task Force for the management of paediatric bronchiectasis sought to identify evidence-based management (investigation and treatment) strategies. It used the ERS standardised process that included a systematic review of the literature and application of the GRADE approach to define the quality of the evidence and level of recommendations.
A multidisciplinary team of specialists in paediatric and adult respiratory medicine, infectious disease, physiotherapy, primary care, nursing, radiology, immunology, methodology, patient advocacy and parents of children/adolescents with bronchiectasis considered the most relevant clinical questions (for both clinicians and patients) related to managing paediatric bronchiectasis. Fourteen key clinical questions (7 “Patient, Intervention, Comparison, Outcome” [PICO] and 7 narrative) were generated. The outcomes for each PICO were decided by voting by the panel and parent advisory group.
This guideline addresses the definition, diagnostic approach and antibiotic treatment of exacerbations, pathogen eradication, long-term antibiotic therapy, asthma-type therapies (inhaled corticosteroids, bronchodilators), mucoactive drugs, airway clearance, investigation of underlying causes of bronchiectasis, disease monitoring, factors to consider before surgical treatment and the reversibility and prevention of bronchiectasis in children/adolescents. Benchmarking quality of care for children/adolescents with bronchiectasis to improve clinical outcomes and evidence gaps for future research could be based on these recommendations.
Background:
Tuberculosis has been linked to an increased risk of atherosclerotic cardiovascular disease (ASCVD). We assessed whether latent tuberculosis infection (LTBI) is associated with subclinical coronary atherosclerosis in two TB-prevalent areas.
Methods:
We analyzed cross-sectional data from studies conducted in Lima, Peru, and Kampala, Uganda. Individuals ≥40 years old were included. We excluded persons with known history of ASCVD events or active TB. Participants underwent QuantiFERON®-TB (QFT) testing to define LTBI, and computed tomography angiography to examine coronary atherosclerosis. A Coronary Artery Disease-Reporting Data System (CAD-RADS) score ≥3 defined obstructive CAD (plaque causing ≥50% stenosis).
Results:
113 persons with LTBI and 91 persons without LTBI were included. There were no significant differences between LTBI and non-LTBI participants in terms of age (median [interquartile range]; 56 [51-62] vs. 55 [49-64], p=0.829), male sex (38% vs. 42%; p=0.519), or 10-year ASCVD risk scores (7.1 [3.2-11.7] vs. 6.1 [2.8-10.8]; p=0.533). CAD prevalence (any plaque) was similar between groups (29% vs. 24%; p=0.421). Obstructive CAD was present in 9% of LTBI and 3% of non-LTBI individuals; p=0.095. LTBI was associated with obstructive CAD after adjusting for ASCVD risk score, HIV status, and study site (adjusted odds ratio, 4.96, 95% CI 1.05-23.44; p=0.043). Quantitative QFT TB antigen minus nil interferon-gamma responses were associated with obstructive CAD (adjusted odds ratio, 1.2, 95% CI 1.03-1.41; p=0.022).
Conclusions:
LTBI was independently associated with an increased likelihood of subclinical obstructive CAD. Our data indicates that LTBI is a non-traditional correlate of ASCVD risk.
Background
People who survive tuberculosis face clinical and societal consequences after recovery, including increased risks of recurrent tuberculosis, premature death, reduced lung function, and ongoing stigma. To describe the size of this issue, we aimed to estimate the number of individuals who developed first-episode tuberculosis between 1980 and 2019, the number who survived to 2020, and the number who have been treated within the past 5 years or 2 years.
Methods
In this modelling study, we estimated the number of people who survived treated tuberculosis using country-level WHO data on tuberculosis case notifications, excluding those who died during treatment. We estimated the number of individuals surviving untreated tuberculosis using the difference between WHO country-level incidence estimates and notifications, applying published age-stratified and HIV-stratified case fatality ratios. To estimate survival with time, post-tuberculosis life tables were developed for each country-year by use of UN World Population Prospects 2019 mortality rates and published post-tuberculosis mortality hazard ratios.
Findings
Between 1980 and 2019, we estimate that 363 million people (95% uncertainty interval [UI] 287 million–438 million) developed tuberculosis, of whom 172 million (169 million–174 million) were treated. Individuals who developed tuberculosis between 1980 and 2019 had lived 3480 million life-years (95% UI 3040 million–3920 million) after tuberculosis by 2020, with survivors younger than 15 years at the time of tuberculosis development contributing 12% (95% UI 7–17) of these life-years. We estimate that 155 million tuberculosis survivors (95% UI 138 million–171 million) were alive in 2020, the largest proportion (47% [37–57]) of whom were in the WHO South-East Asia region. Of the tuberculosis survivors who were alive in 2020, we estimate that 18% (95% UI 16–20) were treated in the past 5 years and 8% (7–9) were treated in the past 2 years.
Interpretation
The number of tuberculosis survivors alive in 2020 is more than ten times the estimated annual tuberculosis incidence. Interventions to alleviate respiratory morbidity, screen for and prevent recurrent tuberculosis, and reduce stigma should be immediately prioritised for recently treated tuberculosis survivors.
Funding
UK Medical Research Council, the UK Department for International Development, the National Institute for Health Research, and the European and Developing Countries Clinical Trials Partnership.
Prevalence and Population Attributable Risk for Chronic Airflow Obstruction in a Large
Multinational Study - BOLD Study
Rationale: The Global Burden of Disease programme identified smoking, and ambient and household air pollution as the main drivers of death and disability from Chronic Obstructive Pulmonary Disease (COPD). Objective: To estimate the attributable risk of chronic airflow obstruction (CAO), a quantifiable characteristic of COPD, due to several risk factors. Methods: The Burden of Obstructive Lung Disease study is a cross-sectional study of adults, aged≥40, in a globally distributed sample of 41 urban and rural sites. Based on data from 28,459 participants, we estimated the prevalence of CAO, defined as a post-bronchodilator one-second forced expiratory volume to forced vital capacity ratio < lower limit of normal, and the relative risks associated with different risk factors. Local RR were estimated using a Bayesian hierarchical model borrowing information from across sites. From these RR and the prevalence of risk factors, we estimated local Population Attributable Risks (PAR). Measurements and Main Results: Mean prevalence of CAO was 11.2% in men and 8.6% in women. Mean PAR for smoking was 5.1% in men and 2.2% in women. The next most influential risk factors were poor education levels, working in a dusty job for ≥10 years, low body mass index (BMI), and a history of tuberculosis. The risk of CAO attributable to the different risk factors varied across sites. Conclusions: While smoking remains the most important risk factor for CAO, in some areas poor education, low BMI and passive smoking are of greater importance. Dusty occupations and tuberculosis are important risk factors at some sites.
Objective
Data on cognitive changes in patients of tuberculous meningitis (TBM) are sparse. We aimed to study the cognitive profile of grade I TBM patients and correlate with the cytokine values.
Methods
Prospectively 60 (M:F-31:29) patients of grade I TBM were recruited. Clinical details, CSF estimation of cytokines, neuropsychological assessment was done and correlation were done.
Results
Mean age of presentation and duration of symptoms were 32.2 (32.2 ± 10.1) years and 29.9 (29.9 ± 25.9) days respectively. Definitive evidence of mycobacterial infection was observed in 28.3%. Mean levels of tumor necrosis factor-α (TNF-α), interferon (IFN-γ) and interleukin-6 (IL-6) were 11.57 ± 30.35, 197.02 ± 186.64, and 127.03 ± 88.71 pg/mL respectively. TNF-α levels were significantly elevated in definitive TBM ( p = 0.044). Neuropsychological tests revealed impaired Auditory verbal learning test (88.3%) followed by complex figure test (50%), spatial span test (50%), clock drawing test (48.3%), Digit span test (35%), Color trail test 1 and 2 (30% and 33.3% respectively) and animal naming test (28.3%). Elevated levels of IFN-γ and IL-6 in TBM were directly correlated with the number of impaired neuropsychological tests. During follow up, significant improvement was noticed in Animal naming test ( p = 0.005), Clock drawing test ( p = 0.003), color trail test 2 (0.02), spatial span test ( p = 0.012) and digit span test (0.035). Verbal learning did not show any significant change. Overall Neuropsychological tests showed better recovery of attention, working memory, category fluency and minimal recovery of verbal learning.
Conclusions
There is subclinical evidence of cognitive impairment in patients of TBM and this correlated with elevated cytokines. Both the frontal and temporal lobes show varying degree of cognitive impairment.
ALTHOUGH CURABLE, TB frequently leaves the individual with chronic physical and psycho-social impairment, but these consequences have been largely neglected. The 1st International Post-Tuberculosis Symposium (Stellenbosch, South Africa) was held to discuss priorities and gaps in addressing this issue. A barrier to progress has been the varied terminology and nomenclature, so the Delphi process was used to achieve consensus on definitions. Lack of sufficient evidence hampered definitive recommendations in most domains, including prevention and treatment of post-TB lung disease (PTLD), but the discussions clarified the research needed. A consensus was reached on a toolkit for future PTLD measurement and on PTLD patterns to be considered. The importance of extra-pulmonary consequences and progressive impairment throughout the life-course was identified, including TB recurrence and increased mortality. Patient advocates emphasised the need to address the psychological and social impacts post TB and called for clinical guidance. More generally, there is an urgent need for increased awareness and research into post-TB complications.
BACKGROUND: Evidence on the impact of tuberculosis (TB) treatment on lung function is scarce. The aim of this study was to evaluate post-treatment sequelae in drug-susceptible and drug-resistant-TB (DR-TB) cases in Mexico and Italy. METHODS: At the end of TB treatment the patients underwent complete clinical assessment, functional evaluation of respiratory mechanics, gas exchange and a 6-minute walking test. Treatment regimens (and definitions) recommended by the World Health Organization were used throughout. RESULTS: Of 61 patients, 65.6% had functional impairment, with obstruction in 24/61 patients (39.4%), and 78% with no bronchodilator response. These effects were more prevalent among DR-TB cases (forced expiratory volume in 1 s/forced vital capacity [FEV 1 /FVC] < lower limit of normality, 14/24 vs. 10/34; P = 0.075). DR-TB patients showed moderately severe (FEV 1 < 60%) and severe obstruction (FEV 1 < 50%) ( P = 0.008). Pre- and post-bronchodilator FEV 1 and FEV 1 /FVC (% of predicted) were significantly lower among DR-TB cases. Plethysmography abnormalities (restriction, hyperinflation and/or air trapping) were more frequent among DR-TB cases ( P = 0.001), along with abnormal carbon monoxide diffusing capacity (DLCO) ( P = 0.003). CONCLUSION: The majority of TB patients suffer the consequences of post-treatment sequelae (of differing levels), which compromise quality of life, exercise tolerance and long-term prognosis. It is therefore important that lung function is comprehensively evaluated post-treatment to identify patient needs for future medication and pulmonary rehabilitation.