Abbreviations
- CD4
cluster of differentiation 4
- IGRA
interferon-gamma release assay
- NICE
National Institutes for Health and Care Excellence
- TB
tuberculosis
- TST
tuberculin skin test
Key Messages
Five guidelines were identified that provide recommendations about screening for tuberculosis in people with chronic conditions. These guidelines cover populations with HIV, psoriasis vulgaris, solid organ and stem transplants, chronic inflammation, and compromised immune systems.
Three guidelines recommend regularly screening for latent and active tuberculosis in people diagnosed with HIV or those taking medication that suppresses their immune system.
One guideline for patients with psoriasis recommends using interferon-gamma release assay and a chest X-ray to rule out tuberculosis infection before immunosuppressant treatment is initiated and during treatment.
Two guidelines recommend using both the interferon-gamma release assay and the tuberculin skin test at the same time to screen for latent tuberculosis infection in people with HIV, people with or who need an organ or stem cell transplant, and in people taking medication that suppresses their immune system.
One guideline for people living with HIV recommends using a rapid nucleic acid amplification test to confirm clinical suspicions of active tuberculosis in these patients.
Context and Policy Issues
Individuals with medical conditions that compromise their immune system, such as those with organ transplants, have a higher risk of an infection with tuberculosis (TB).1 These patients are not always screened for TB before treatment, and there is interest in knowing what the recommendations are regarding screening for TB in patients with existing chronic health conditions that compromise the immune system.
In July 2020, CADTH searched the literature for evidence-based guidelines regarding TB screening for populations with existing chronic conditions.2 This report identified 1 systematic review of guidelines3 and 6 evidence-based guidelines4–9 that met the inclusion criteria based on their title and abstract. The purpose of the current report is to review the full texts of these publications, and to summarize and critically appraise the eligible publications.
This report is a component of a larger CADTH Condition Level Review on Tuberculosis. A condition level review is an assessment that incorporates all aspects of a condition, from prevention, detection, treatment of the patient, and management of the disease. For more information on CADTH’s Condition Level Review of Tuberculosis, please visit the project page (https://www.cadth.ca/tuberculosis).
Research Question
What are the evidence-based guidelines regarding tuberculosis screening for populations with existing chronic conditions?
Methods
Literature Search Methods
A limited literature search was conducted for a previous CADTH report2 by an information specialist on key resources including PubMed, the Cochrane Library, the University of York Centre for Reviews and Dissemination databases, the websites of Canadian and major international health technology agencies, as well as a focused internet search. The search strategy comprised both focused controlled vocabulary (wherein the terms appeared in major subject headings only), such as the National Library of Medicine’s MeSH (Medical Subject Headings), and keywords. The main search concepts were tuberculosis, screening, and chronic conditions. Search filters were applied to limit retrieval to health technology assessments, systematic reviews, meta-analyses, or network meta-analyses, and guidelines. Where possible, retrieval was limited to the human population. The search was also limited to English language documents published between January 1, 2010 and June 24, 2020. Internet links were provided, where available.
Selection Criteria and Methods
The evidence in this report was identified in a previous CADTH report,2 where 1 reviewer screened citations and abstracts. For this report, the full-text articles were reviewed by 1 reviewer and the final selection of full-text articles was based on the inclusion criteria presented in .
Exclusion Criteria
Articles were excluded if they did not meet the selection criteria outlined in , they were duplicate publications, or were published before 2010. Guidelines with unclear methodology were also excluded.
Critical Appraisal of Individual Studies
The included publications were critically appraised by 1 reviewer using the following tool as a guide: the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument.10 Summary scores were not calculated for the included studies; rather, the strengths and limitations of each included publication were described narratively.
Summary of Evidence
Quantity of Research Available
A total of 550 citations were identified in the literature search for the previous CADTH report2 and 2 potentially relevant publications were retrieved from the grey literature. Seven potentially relevant reports were identified and retrieved for full-text review. Of these potentially relevant articles, 2 publications were excluded (1 systematic review of guidelines3 did not provide the detailed recommendations from the guidelines, and 1 review did not follow a systematic approach7), and 5 evidence-based guidelines4–6,8,9 met the inclusion criteria and were included in this report.
Summary of Study Characteristics
Five evidence-based guidelines4–6,8,9 were identified and included in this report, and are summarized below. Additional details regarding the study characteristics are provided in tables in Appendix 1.
One guideline published in 2019 was a joint guideline by the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America (CDC/NIH/HIV MAIDSA)4; this guideline is meant to apply to the US . The German guideline for the treatment of psoriasis vulgaris was published in 2018, and is meant to apply to Germany.8 There were 2 guidelines published in 2016; the guideline by the National Institute for Health Care Excellence (NICE)5 is meant to apply to the UK, and a joint guideline by the Spanish Society of Infectious Diseases and Clinical Microbiology and the Spanish Society of Respiratory Diseases and Thoracic Surgery (SEIMC/SEPAR)9 is meant to apply to Spain. A WHO guideline was published in 2013 and is meant to apply globally. One guideline8 was specific for patients with psoriasis vulgaris. Three guidelines5,6,9 covered a broader population than the current report (i.e., the general population with or at risk of TB), which included individuals with HIV or other conditions that compromise the immune system (e.g., chronic inflammation). The other guideline4 was specific to individuals with HIV. The interventions considered within guidelines were broader than the eligible interventions for this report. The interventions that were relevant to this report included screening strategies, the tuberculin skin test (TST), and the interferon-gamma release assay (IGRA).4–6,8,9
Summary of Critical Appraisal
The critical appraisal of the included guidelines is summarized below and additional details are provided in.
Two of the guidelines5,9 in this report were previously included in CADTH reports on guidelines for the treatment of TB11 or for TB in people with compromised immunity.12 The detailed critical appraisal of these guidelines can be found in those reports. In brief, both the NICE guideline5 and the SEIMC/SEPAR guideline9 used high-quality systematic methods to search for evidence and develop the recommendations.
Overall, the methodology for the CDC/NIH/HIV MAIDSA guideline4 was poorly reported, reducing the quality of guideline and the certainty in the recommendations. The objective of the guideline, the population of interest, and target users were clearly reported, but the research questions covered by the guideline were not specifically described. While it was reported that guideline working group members were responsible for searching for evidence using systematic reviews, no other methods were specified. Thus, it is unknown whether systematic approaches were used for searching for, selecting, or evaluating the evidence. In addition, the methods for formulating the recommendations were not reported, nor were specific links between the recommendations and supporting evidence provided. The source of funding was reported, but it was unclear whether the funder influenced the guideline. All members of the guideline development group declared potential conflicts of interest, which were reviewed to determine if members were disqualified from contributing to certain portions of the guideline, thus reducing the risk of bias due to financial or personal conflicts of interest.
The guideline for psoriasis vulgaris8 included in this report is a shorter version of a longer German guideline, which was not accessible for this report. The guideline reported that certain components, such as the aim of the guideline, detailed methodology, and instructions on using the guideline, are reported in the longer version of the guideline, and as it was not available in English, it is was not possible to assess these aspects. The members of the guideline development, their affiliations, and their roles were reported, and there were patient representatives in the guideline development group, although how the patients contributed was not reported. The methodology used to search for evidence in this guideline varied by topic, and for the section of the guideline that was relevant to this report (i.e., screening for TB), no systematic search for evidence was conducted and the recommendations were generated through consensus among experts, limiting the confidence in these recommendations. The source of funding was reported and it was reported that the funder had no influence on the recommendations. All members of the guideline development group declared their potential conflicts of interest, and specific criteria were used to mitigate these conflicts.
The WHO guideline6 had a clear description of the scope of the guideline, the health questions covered, the population to whom the guideline was meant to apply, and the target users of the guideline. This guideline used a systematic approach to search for and select the evidence, and the explicit link between the recommendations and supporting evidence were reported. Although the systematic review conducted to address the research questions relevant to the current report did not describe the quality or risk of bias in the included studies, the guideline included an evaluation of the overall quality of the evidence following standard methods (i.e., Grading of Recommendations, Assessment, Development and Evaluations or GRADE), which included an assessment of the study limitations. The methods for developing the recommendations from the evidence were briefly described, and additional details would improve the understanding of how the final decisions were made. In addition, it was not reported whether the views of target population were sought in developing the recommendations. The source of funding was reported, but it was unclear whether the funder influenced the guideline. It was reported that none of the experts declared any conflicts of interest that were judged to significantly affect the development of the recommendations.
Summary of Findings
Additional details regarding the main study findings and authors’ conclusions are provided in tables in Appendix 1.
Guidelines Regarding Tuberculosis Screening in Populations with Existing Chronic Conditions
Five evidence-based guidelines4–6,8,9 included recommendations regarding screening for TB in populations with chronic health conditions.
Screening for Latent Tuberculosis Infection in People with HIV
The CDC/NIH/HIV MAIDSA guideline4 recommends that all people with HIV should be tested for latent tuberculosis infection (LTBI), at the time of their HIV diagnosis; this is a strong recommendation based on 1 or more well-designed study. The CDC/NIH/HIV MAIDSA guideline4 also recommends that people with HIV who are at high risk of exposure to TB should receive annual testing for LTBI using TST; this is a strong recommendation based on expert opinion.
For patients with HIV and cluster of differentiation 4 (CD4) counts of fewer than 200 cells/mm3, the NICE guideline5 recommends testing for LTBI using an IGRA with a concurrent TST, and if either test is positive to assess for active TB; this recommendation was based off of low- to high-quality evidence, and made with the certainty that for the vast majority of patients this screening approach will do more good than harm.
The SEIMC/SEPAR guideline9 recommends that people with HIV are screened for LTBI using both the IGRA and the TST; however, in patients with HIV and a CD4 count of fewer than 200 cells/mm3 this guideline recommends only using IGRA; this is a weak recommendation based on low-quality to very low-quality evidence.
Screening for Active Tuberculosis in People with HIV
The WHO guideline,6 recommends that people living with HIV be screened for active TB at each visit to a health facility; this is a strong recommendation based on very lowquality evidence.
If a patient with HIV is suspected of having active TB, the NICE guideline5 recommends using a rapid nucleic acid amplification test for diagnosis; this recommendation is based on very low-quality evidence, but it is made with the certainty that for the vast majority of patients this testing approach will do more good than harm.
Screening for Tuberculosis in People who Require Treatment with a Biologic Therapy
For patients with psoriasis vulgaris, the guideline 8 recommends that IGRA and a chest X-ray are used to screen for TB before initiating treatment with immunosuppressants; this is a strong recommendation based on expert opinion.
For patients with chronic inflammatory disease, the SEIMC/SEPAR guideline9 recommends screening for LTBI using both the TST and an IGRA before starting biologic therapy; this is a weak recommendation based on low-quality to very low-quality evidence.
The guideline for psoriasis vulgaris8 also recommends repeating the IGRA and chest X-ray during treatment with biologic therapy, if there is a suspicion that the patient may be infected with TB (i.e., TB reactivation or new infection); this is a strong recommendation based on expert opinion.
Screening for Tuberculosis in People with Other Forms of Compromised Immunity
For patients who will undergo a solid organ or stem cell transplant, the SEIMC/SEPAR guideline9 recommends that patients are screened for LTBI using both the TST and an IGRA before transplantation; this is a weak recommendation based on very low-quality evidence.
For adults who are severely immunocompromised, such as those who have had a solid organ or stem cell transplant, the NICE guideline5 recommends testing for LTBI using an IGRA with a concurrent TST, and if either test is positive to assess for active TB; this recommendation was based on low to high-quality evidence, and made with the certainty that for the vast majority of patients this screening approach will do more good than harm.
For adults who are immunocompromised, the NICE guideline5 recommends testing for LTBI using the IGRA alone or with a concurrent TST, and if either test is positive to further assess the patient for active TB; this recommendation was based off of low- to high-quality evidence and made with the certainty that for most patients this testing strategy will do more good than harm.
Limitations
The findings in this report are limited by the quality of evidence. While 2 guidelines5,9 used high-quality methods to develop their recommendations, 1 guideline6 did not report sufficient detail of the methodology used to develop the recommendations and was assessed to be of moderate quality, and the other 2 guidelines did not use systematic methods for searching for evidence and were assessed to be of low quality.4,8 In addition, the relevant recommendations in the guidelines were based primarily on expert opinion or low-quality evidence, which reduces the certainty of the recommendations summarized in this report.
This report identified recommendations for TB screening in people with HIV, those requiring a biologic therapy (e.g., psoriasis vulgaris), and individuals who have had or who require a solid organ or stem cell transplant but did not identify recommendations for all chronic conditions (e.g., diabetes or end-stage renal disease); and thus, the recommendations regarding screening for TB in populations with those conditions is unknown.
While 1 of the guidelines6 is meant to apply globally, none of the guidelines are specific to Canada, and it is unknown whether recommendations from guidelines developed outside of Canada are generalizable to the Canadian clinical practice, as there may be geographical differences between countries with regard to access to care for these chronic conditions, and for the availability of screening tests for TB.
Conclusions
This report comprises 5 evidence-based guidelines4–6,8,9 that included recommendations regarding screening for TB in individuals with chronic health conditions.
With regard to screening strategies for TB, in patients with HIV, 1 guideline4 recommended that patients are screened for LTBI upon diagnosis of HIV, and annually thereafter. To test for a LTBI in people with HIV, 1 guideline9 makes a weak recommendation (based on low-quality to very low-quality evidence) to use both the IGRA and TST tests, unless patients have a CD4 count of fewer than 200 cells/mm3, in which case only the IGRA is recommended. This is contradicted by a strong recommendation (based on low to high-quality evidence) made by another guideline,5 which recommends using the IGRA and a concurrent TST to test for LTBI in patients with HIV who have a CD4 count of fewer than 200 cells/mm3.
It is also recommended that people with HIV are screened for active TB at each health care visit.6 If a patient with HIV is suspected of having active TB it is recommended that a rapid nucleic acid amplification test is used to diagnosis active TB in this population.5
In patients with psoriasis vulgaris, 1 guideline8 recommends screening for TB using IGRA and a chest X-ray before initiating treatment with immunosuppressants, and during treatment with biologic therapy, if there is a suspicion that the patient may be infected with TB. Screening for LTBI using TST and IGRA before starting biologic therapy was also recommended by 1 guideline9 for patients with chronic inflammation.
In patients who require or who have received a solid organ or stem cell transplant, screening for LTBI using IGRA with a concurrent TST is recommended, before9 and after5 transplantation.
Although the recommendations in this report are associated with a moderate degree of uncertainty due to the quality of reporting in the guidelines and the reliance on expert opinion or low-quality evidence, which should be considered when interpreting the findings of this report, most of the recommendations were strong, and made with the certainty that the interventions would do more good than harm for most patients.
Overall, the recommendations suggest that in populations with chronic conditions that compromise the immune system, patients should be screened for TB upon diagnosis of the condition, before initiating treatment, and regularly throughout their care. In most cases, it is recommended to test for LTBI using the IGRA concurrently with the TST, or the IGRA alone. A chest X-ray is recommended to screen for active TB, and it is recommended that a rapid nucleic acid amplification test is used to confirm clinical suspicions of active TB.
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Funding: CADTH receives funding from Canada’s federal, provincial, and territorial governments, with the exception of Quebec.
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