Background

The World Health Organization (WHO)1 reports that tuberculosis (TB) has been a leading cause of global mortality and morbidity for many years. The National Institute of Allergy and Infectious Diseases (NIAID)2 and the Centers for Disease Control and Prevention (CDC)3 define TB as a contagious and severe airborne disease that is bacterial in nature. It is caused by the bacteria Mycobacterium tuberculosis and can present itself as pulmonary or extra-pulmonary infection.2,3 Pulmonary TB is defined by the CDC3 and Lee4 as TB infection of the lungs. Extra-pulmonary TB is defined by Lee4 as TB infection that involves organs other than the lungs. Pulmonary TB is more common than extra-pulmonary TB.4 People with TB present with symptoms such as chest pain, coughing up of blood, weakness or fatigue, weight loss, poor appetite, chills, fever and night sweats.3 According to the CDC,3 people with human immunodeficiency virus (HIV) are at high risk of contracting TB due to their suppressed immune systems, and this may significantly shorten their lifespan, if not managed effectively. Gao et al.5 recently reported prevalence rates for TB and HIV co-infection: 31.25% in African countries, 17.21% in Asian countries, 20.11% in European countries, 25.06% in Latin America countries and 14.84% in United States of America. Multidrug-resistant TB is defined by NIAID2 as a disease in which TB bacteria do not respond to antibiotics commonly used to cure TB. As a result, this type of TB is more difficult to treat than ordinary TB.2 Extensively drug-resistant TB is, according to NIAID,2 a form of multidrug-resistant TB that is less common but very difficult to manage and patients typically need two years of extensive drug treatment before cure can be confirmed. The Stop TB strategy, one of the Millennium Development Goals established by WHO in 2000,1 has been successful in reducing the global mortality associated with TB infection by 47% and lowering the global incidence of TB by 18% since 2000, as reported in 2015.1 Despite several advances made in the detection and management of TB, it remains a leading cause of death, alongside HIV infection.1 The WHO1 reports that the incidence of multidrug-resistant TB and extensively drug-resistant TB continues to increase and not all cases are diagnosed or successfully treated. Research in TB has focused mainly on preventing infection through the development of TB vaccines, facilitating accurate diagnosis through the development of more accurate diagnostic tools and developing new anti-TB drugs to treat infected individuals more effectively.1

Dheda et al.6 describes the anatomical changes that take place in lung tissue as a result of TB infection. These changes include cavitation formation and tissue necrosis that eventually heal through the development of extensive fibrosis of lung tissue and bronchiectasis.6 Dheda et al.6 and Dandekar and Dixit7 concur that these permanent structural changes in the lung lead to lung volume loss and impaired gas exchange, which increases patient morbidity and reduces their work capacity. Dandekar and Dixit7 report unemployment rates of more than 50% in their patients with TB infection. Such high unemployment rates might impact negatively on a country's economic status. Caronia8 states that the reductions in lung volume and impaired gas exchange that people with TB infection experience lead to decreased diffusion of oxygen at the blood-lung interface and contributes significantly to exercise-induced desaturation and symptoms of breathlessness. These respiratory symptoms might not only impact employment rates but the ability of people with TB to function optimally in their daily lives and in society. Masumoto et al.9 found that factors such as unemployment and higher levels of dyspnea (breathlessness) were associated with lower health-related quality of life (HRQoL) related to physical function.

Several researchers10-12 investigated the effect of active TB infection on HRQoL in those with pulmonary TB. They10-12 describe the significant deficits that people with TB infection report in relation to physical, psychological and social aspects of HRQoL. Brown et al.10 showed that people with active TB have lower health status, particularly in relation to physical function, when HRQoL is compared to populations that do not have TB. They reported that those with TB and HIV co-infection have lower health status compared to those with TB who are HIV-negative.10 Brown et al.10 also reported that when TB treatment is completed, many people still suffer long-term physical sequelae of TB. This observation was confirmed by Guo et al.11 who reported that although anti-TB therapy has a positive effect on improving HRQoL for people with TB, their HRQoL status related to physical function and mental health remains significantly lower than that of the general population or those with latent TB after completion of therapy and microbiological cure of the disease. Atif et al.12 found that although anti-TB therapy improved their patients HRQoL over time, they still presented with compromised physical and mental health at the end of their treatment, with more than 23% at risk of developing depression. Ralph et al.13 reported that patients with pulmonary TB had significantly lower exercise endurance, more respiratory symptoms and impaired lung function compared to a healthy control group when assessed after six months of anti-TB therapy. According to Singla et al.,14 people with multidrug-resistant TB who successfully completed their TB therapy, still present with symptoms of breathlessness, abnormal chest X-ray features and impaired lung function.

It is not clear as to what extent limitations in physical function outcomes, such as muscle strength, joint range of motion, mobility, breathlessness, lung function, control of balance and exercise capacity, and limitations in activity participation outcomes, such as performance of activities of daily living, impact on the HRQoL of people with TB infection. The WHO International Classification of Functioning, Disability and Health15 identifies problems in body function and structure as impairments and difficulties with tasks or actions as activity limitations. Physical impairments were assessed by Egede16 and Waddell et al.17 in other patient populations through the use of physical tests such as measurement of joint range of motion, muscle strength, proprioception, balance control, mobility, sensation, pain and exercise capacity. Physical impairments related to pulmonary function in the TB population were assessed by Masumoto et al.9 using the Medical Research Council dyspnea scale and by Ralph et al.13 and Singla et al.14 using lung function tests. Activity limitations were identified in several patient populations through the use of questionnaires such as the Functional Independence Measure18 and the Barthel Index19 to assess patients' abilities to perform activities of daily living such as bathing, dressing, performing transfers and more. For the purposes of this review, physical impairments are defined as impairment in a person's physical functioning (including muscle strength or joint range of motion), mobility (including balance control and proprioception), sensation, breathing ability (level of dyspnea or breathlessness, lung function test results) and exercise capacity. Activity limitations or functional impairments are defined as difficulty performing activities of daily living.18,19

It is important to examine and map the existing research to better understand the relationships between TB infection, anti-TB therapy and HRQoL in relation to physical impairments and activity limitations in this patient population. The types of rehabilitation strategies that are currently in place for people with TB infection to aid in the treatment of physical impairments and activity limitations are equally important to examine. The target population is: people with active or multidrug-resistant pulmonary or extra-pulmonary TB who are receiving anti-TB therapy or have completed anti-TB therapy.

This scoping review will provide a map of the type, extent and quantity of research available regarding the physical impairments and activity limitations that people with pulmonary or extra-pulmonary TB infection experience while receiving anti-TB therapy or after completion of anti-TB therapy and the rehabilitation strategies used to address these factors. It will identify any shortcomings in the existing literature through the extraction of particular information from the included studies. Exploration of social functioning and mental health impacts on HRQoL of people with TB infection is beyond the scope of this review. This review will follow the Joanna Briggs Institute (JBI) Scoping Review methodology outlined in the 2015 JBI Reviewers' Manual.20,21 The PRISMA22 flow diagram will be used in the presentation of the results of the scoping review.

An initial search of the literature, using PubMed and Google Scholar, was conducted to determine whether there are studies with findings available to answer the research question and whether there is a systematic or scoping review currently underway or published that addresses the knowledge gap. The question posed by this review is unique as no systematic or scoping reviews addressing this question could be found.

Inclusion criteria

Types of participants

The current review will consider all studies that focus on adults of working age (age range: 18-60 years) with diagnosed TB infection with or without HIV co-infection. Adults between 18 and 60 years are economically active and contribute toward the financial wellbeing of the countries that they live in. Therefore, impairments in their physical function and activity participation might have a negative impact on economic growth. Studies will also be included where adults with TB infection are part of a larger sample of patients with restrictive lung diseases but where it is possible to accurately identify data, which is from adults with TB infection, separately. Infection with HIV as well as any co-morbidities listed by others in the TB population that may impact their physical function and activity participation will be treated as confounding variables for this review. Pediatric patients with TB infection will not be included in this review.

Concept

The current scoping review will consider studies that report on physical impairments and activity limitations experienced by adults as a result of TB infection. Tuberculosis infection, when diagnosed by a healthcare professional using standard diagnostic criteria, and drug-resistant TB, whether pulmonary or extra-pulmonary, will be considered for the review. Physical impairments and activity limitations, diagnosed by a healthcare professional using standard diagnostic criteria, that will be reported on include, but are not limited to:

* Muscle strength

* Joint range of motion

* Mobility

* Balance

* Pro-prioception

* Activities of daily living

* Fatigue

* Exercise capacity/endurance

* Pain

* Breathlessness

* Lung function tests

* Sensation

Context

The current scoping review will consider research studies conducted in primary, acute or community healthcare settings. It will not be limited to specific geographic locations or racial or gender-based interests.

Types of sources

The current scoping review will consider both qualitative and quantitative data.

Quantitative

The current review will include systemic reviews, meta-analyses, experimental and observational studies (randomized-controlled trials, non-randomized controlled trials, quasi-experimental, pre- and post-test designs and prospective and retrospective cohort studies), case-control studies, and analytical and descriptive cross-sectional studies.

Qualitative

The current review will include data obtained from qualitative studies including, but not limited to, designs such as phenomenology, grounded theory and ethnography.

Opinion papers and letters will be excluded as these will not be particularly useful to meet the objectives of this review.

Search strategy

The search strategy aims to find both published and unpublished studies. A three-step search strategy will be utilized in this review. An initial limited search of MEDLINE and CINAHL will be undertaken followed by analysis of the text words contained in the title and abstract of retrieved papers, and of the index terms used to describe the articles. A second search using all identified keywords and index terms will then be undertaken across all included databases. Third, the reference lists of all included articles and reports will be searched to identify additional sources of relevant information. In addition, hand searching in key journals such as Tuberculosis, International Journal of Tuberculosis and Lung Disease, Journal of Tuberculosis Research and New England Journal of Medicine will be performed. Reviewers intend to contact authors of primary studies or reviews for further information if this is relevant. Gray literature (unpublished) and conference papers will also be searched.

Articles will be assessed for inclusion based on the inclusion criteria outlined above, examining them by title and abstract. If an article meets the inclusion criteria, or if further examination of the article is required before exclusion, the full text of the article will be retrieved. Two reviewers will independently confirm if the full-text article meets the inclusion criteria. Any disagreement will be resolved by a third reviewer.

All studies published in the English language will be considered for inclusion in this scoping review. Studies published from the inception of each database to the present time will be included in the review.

Databases

Databases to be searched for published studies:

* MEDLINE

* Scopus

* Embase

* CINAHL Plus

* LILACS

* Cochrane Database of Systematic Reviews

* Campbell Collaboration Library

The search for unpublished studies will include:

* Google Scholar

* Open Grey

* Publications from relevant organizations such as Stop TB Partnership, WHO, TB Care I (USAID), The International Union against Tuberculosis and Lung Disease and the TB Centre (London School of Hygiene & Tropical Medicine) will be searched for information.

Search terms

The initial search terms include pulmonary TB, extra-pulmonary TB, drug-resistant TB, HIV co-infection, physical impairments, activities of daily living; mobilization, walking, exercise endurance, exercise tolerance, muscle strength, muscle power, muscle cross-sectional area, balance, gait, joint range of motion, dyspnoea, breathlessness, lung function test, anti-TB therapy, pro-prioception, sensation, fatigue, pain and activity limitations.

Data extraction

Data extraction from papers included in the review will be done using a data charting tool tailored to the purposes of this scoping review (Appendix I). Multiple articles from the same project/program will be linked and treated as one for the purposes of data extraction and of presenting the results. The two reviewers will independently extract data from the first five studies onto the data charting form. They will then meet to determine if their method of data extraction is consistent with the review question and purpose. Reviewers may review one study several times within this stage. Thereafter, the two reviewers will extract data independently. Any disagreement will be discussed with and resolved by a third reviewer. Charting of the results is an iterative process, and therefore the data charting tool will be further refined at the review stage and updated accordingly.

Presenting the data

The number of studies found, included and excluded will be shown in a PRISMA22 flow diagram. Results will be presented as a map of the data in a logical, diagrammatic or tabular form and in a descriptive format that aligns to the objectives and scope of the review. The results summary will logically describe the aims and/or purposes of the reviewed sources, the methodologies applied and any results that relate to the review questions. The results will be classified under main conceptual categories (e.g. impairments in muscle strength or limitations in ambulation) that will be obtained during the results extraction. For each category, a clear explanation will be provided.

Appendix I: Data charting tool

Study participants and characteristics extraction (Level 1):

* Authors and year published

* Number of participants

* Age

* Gender

* Location

* Source of results (e.g. study design, methods)

* Healthcare setting

Results extraction (Level 2):

* Type of TB

* HIV co-infection

* Other morbidities

* Type of physical impairments

* Type of activity limitations

* How impairments were assessed

* Type of anti-TB therapy received

* Duration of time since TB diagnosis

* Type of rehabilitation offered to people with TB

* Level of evidence (using Oxford Centre for Evidence-Based Medicine - Levels of Evidence 2009)

References