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Draft Research Plan

Screening for Latent Tuberculosis Infection in Adults


Note: This is a draft Research Plan. This draft is distributed solely for the purpose of receiving public input. It has not been disseminated otherwise by the USPSTF.

The final Research Plan will be used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Report will form the basis of the USPSTF Recommendation Statement on this topic.

This draft Research Plan is available for comment from June 5 until July 2, 2014 at 5:00 p.m., ET. You may wish to read the entire Research Plan before you comment.


I. Proposed Analytic Framework

Select Text Description below for details.

Abbreviations: IGRAs = interferon-gamma release assays; KQ = key question; LTBI = latent tuberculosis infection; TB = tuberculosis; TST = tuberculin skin test.

[D] Select for Text Description.

II. Proposed Key Questions to Be Systematically Reviewed

1. What is the direct evidence that targeted screening for latent tuberculosis infection (LTBI) in asymptomatic adults at increased risk for developing active tuberculosis (TB) (such as persons in populations with a high prevalence of active TB or with documented increased risk for progression from LTBI to active TB) in primary care settings improves quality of life and reduces the incidence of active TB infection, transmission of TB, and mortality?

2a. What is the accuracy and reliability of using either tuberculin skin tests (TSTs) or interferon-gamma release assays (IGRAs) for screening asymptomatic adults who are at increased risk for developing active TB?

2b. What is the accuracy and reliability of using sequential screening strategies (e.g., TST followed by IGRA for persons with a particular TST result) in adults who are at increased risk for developing active TB?

3. For adults with LTBI, to what extent does treatment using Centers for Disease Control and Prevention (CDC)–recommended pharmacotherapy regimens improve quality of life and reduce progression to active TB, transmission of TB, and mortality?

4. What harms (including false-positive results, anxiety, labeling, and stigma) are associated with screening for LTBI?

  1. How do the harms differ by screening method or screening strategy?
  2. How do the harms differ by population screened?

5. What are the harms associated with treatment of LTBI using CDC-recommended pharmacotherapy regimens?

III. Proposed Contextual Questions

Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

  1. What are the estimated U.S. adult prevalence rates of LTBI and active TB in populations at increased risk for TB receiving care in primary care settings, including limitations or uncertainties regarding these prevalence rate estimates?
  2. What proportion of U.S. adults receiving care in primary care settings are members of these populations at increased risk?
  3. What proportion of active TB cases in U.S. adults originate in these populations at increased risk?
  4. What is the evidence on the incremental net benefit of more or less frequent screening for LTBI using different screening intervals in adults at increased risk in primary care settings?
  5. What is the reported frequency of LTBI screening in U.S. adults in primary care settings, both overall and for populations at increased risk?

IV. Proposed Research Approach

The Proposed Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Report. Criteria are overarching as well as specific to each of the key questions (KQs).

  Include Exclude
Populations Asymptomatic adults belonging to populations at increased risk* Children and adolescents; symptomatic adults with active TB

Persons with HIV, head and neck cancer, silicosis, and history of organ transplant; persons for whom screening and treatment of LTBI would be part of standard disease management such as those taking TNF-α inhibitors

KQ 1: Studies in occupational health settings; studies on close contacts of persons with active TB
Setting Studies conducted in primary care settings in countries categorized as “Very High” on the Human Development Index (as defined by the United Nations Development Program) Prisons, HIV clinics, subspecialty clinics (e.g., oncology clinics)

KQ 1: Studies in occupational health settings

Screening Screening using TST or IGRA; studies using a single screening test or multiple tests in series (e.g., TST followed by IGRA for persons with potentially significant TST results) Other screening tests
Treatment/Management interventions Isoniazid, rifampin, or isoniazid plus rifapentine regimens recommended by the CDC (self-administered at home or by directly observed therapy) Other treatments or combinations
Comparisons KQ 1: Screened vs. nonscreened groups

KQ 2: Studies on screening accuracy assessing the sensitivity of TST or IGRA in a sample of persons with microbiologically confirmed active TB, or assessing specificity in a sample of healthy persons with low risk of TB and without known exposure to TB; studies assessing IGRA using TST as the reference standard; studies on screening reliability must include measures of reproducibility (e.g., test-retest, comparisons between different laboratories or readers)

KQ 3: Primary studies comparing treatment with placebo, no treatment, delayed screening/treatment, or another eligible treatment; systematic reviews including head-to-head comparisons

KQ 4: Screened vs. nonscreened groups

KQ 5: Primary studies comparing treatment with placebo, no treatment, or another eligible treatment; systematic reviews including head-to-head comparisons

No comparison; nonconcordant historical controls; comparisons with treatments not being evaluated in this review
Outcomes KQs 1, 3: Active TB (i.e., progression to active TB); reduction in transmission; quality of life; mortality (TB-specific and overall)

KQ 2: Sensitivity and specificity; reproducibility

KQ 4: False positives leading to unnecessary testing (e.g., chest x-ray) or treatment, stigma, anxiety, cellulitis

KQ 5: Hepatotoxicity (e.g., isoniazid-induced hepatitis); mortality from hepatotoxicity; nausea; vomiting; peripheral neuropathy; development of drug-resistant TB; other specific adverse effects of medications

All other outcomes
Study designs KQ 1: RCTs

KQ 2: Systematic reviews; primary studies published after the included systematic reviews (bridge searches will be performed to determine studies published after the systematic reviews and whether the evidence is consistent with the systematic reviews)

KQ 3: RCTs and systematic reviews

KQ 4: Systematic reviews, RCTs, prospective cohort studies

KQ 5: RCTs, prospective cohort studies, case-control studies, and systematic reviews

Note: Literature searches will include only publications from 1996 or later; if studies published subsequent to 1996 are unable to be identified for the key questions, systematic reviews will be used to identify older studies that are relevant

All other designs
Language English Non-English

* Adult population subgroups at increased risk for developing active TB receiving care in U.S. primary care settings will be defined based on an initial scan of published literature, but may include persons with diabetes, persons who have previously received Bacillus Calmette–Guérin (BCG) vaccination, injection drug users, homeless persons and persons residing in homeless shelters, former prisoners, recent arrivals to the United States (within at least 5 years) from countries with high TB prevalence rates, persons who work with individuals from high prevalence populations, and persons at documented increased risk for progression from LTBI to active TB. Persons with diabetes or who have previously received BCG vaccination will be examined separately for KQ 1; persons who previously received BCG vaccination will be examined separately for KQ 2.
Current CDC-recommended LTBI treatment regimens include the following: isoniazid daily for 6 or 9 months, isoniazid twice weekly by directly observed therapy for 6 or 9 months, rifampin daily for 4 months, or isoniazid plus rifapentine once weekly for 3 months by directly observed therapy. Because of reports of severe liver injury and death, the CDC recommends that rifapentine and pyrazinamide in combination generally should not be offered to treat LTBI.
Only the most recent good-quality systematic reviews for identification of studies presenting effectiveness and harms of LTBI treatment published prior to 1996 will be used.

Abbreviations: CDC = Centers for Disease Control and Prevention; HIV = human immunodeficiency virus; IGRA = interferon-gamma release assay; LTBI = latent tuberculosis infection; RCT = randomized, controlled trial; TB = tuberculosis; TNF-α = tumor necrosis factor-alpha; TST = tuberculin skin test.

AHRQ Publication No. 14-05212-EF-5
Current as of June 2014


Internet Citation:

U.S. Preventive Services Task Force. Screening for Latent Tuberculosis Infection in Adults: Draft Research Plan. AHRQ Publication No. 14-05212-EF-5. http://www.uspreventiveservicestaskforce.org/draftresplan3.htm



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