Practice Guidelines

Tuberculosis: Guidelines for Diagnosis

from the ATS, IDSA, and CDC
symptoms or signs on radiography before initi-
Key Points for Practice
ating LTBI treatment.
•A
 n IGRA is recommended over a TST in persons at least Strong. An IGRA is recommended over a TST
five years of age who are likely to have M. tuberculosis
infection. in persons at least five years of age who are likely
to have M. tuberculosis infection; who are at low
• I f pulmonary TB is suspected, an AFB smear can be per-
formed; three specimens are typically tested. or moderate risk of the disease progressing; in
• I f extrapulmonary TB is suspected, specimens should be whom it has been determined that LTBI testing is
collected from those sites for mycobacterial culture. necessary; and who have been vaccinated against
From the AFP Editors bacillus Calmette-Guérin or are not likely to
return for follow-up after a TST. The TST is a
viable second option in certain circumstances,
Persons with Mycobacterium tuberculosis such as if an IGRA is unavailable.
infection may have no clinical evidence of disease Conditional. An IGRA is recommended over a
and present asymptomatically, known as latent TST in persons at least five years of age who are
tuberculosis infection (LTBI) or symptomati- likely to have M. tuberculosis infection; are at low
cally, known as tuberculosis (TB). TB, which is or moderate risk of the disease progressing; and
a chief cause of infection-related morbidity and in whom it has been determined that LTBI test-
mortality, can be difficult to diagnose. For this ing is necessary. As previously mentioned, a TST
reason, the American Thoracic Society (ATS), is a viable second option. A TST is recommended
Infectious Diseases Society of America (IDSA), over IGRA in healthy children younger than five
and Centers for Disease Control and Prevention years if it has been determined that LTBI testing
(CDC) have provided guidance on diagnosing is necessary.
TB in children and adults. Although recommendations from other
groups indicate that testing for M. tuberculosis
Recommendations infection is not necessary in low-risk persons, it
LTBI TESTING may still be required by local law or for creden-
LTBI testing recommendations are outlined tialing. For this population, an IGRA is recom-
in Table 1. It should be noted that although mended over a TST in persons at least five years
interferon-gamma release assays (IGRAs) of age, with a second test (i.e., IGRA or TST) per-
and tuberculin skin tests (TSTs) can identify formed if the result on the first test is positive.
M. tuberculosis infection, they cannot differen- Infection is confirmed if results on both tests are
tiate between TB and LTBI; therefore, active TB positive. In certain circumstances, TST is a via-
needs to be excluded via presence or absence of ble second option to be performed initially.
Unrated. Evidence is lacking to recommend
TST or IGRA over the other as the first-line test
Coverage of guidelines from other organizations does not in persons at least five years of age who likely
imply endorsement by AFP or the AAFP.
have M. tuberculosis infection and a high risk of
This series is coordinated by Sumi Sexton, MD, Associate
the disease progressing, and in whom it has been
Deputy Editor.
determined that LTBI testing is necessary.
A collection of Practice Guidelines published in AFP is
available at http://www.aafp.org/afp/practguide.
TB TESTING
CME This clinical content conforms to AAFP criteria for
continuing medical education (CME). See CME Quiz on Strong. If pulmonary TB is suspected, an acid-
page 12. fast bacilli (AFB) smear can be performed; three
Author disclosure: No relevant financial affiliations. specimens are typically tested. False results are
common with AFB smears; therefore, a negative

56 
Downloaded from the
American American
Family Family Physician website at www.aafp.org/afp.
Physician Copyright © 2018 American Academy of
www.aafp.org/afp Family 97,
Volume Physicians.
NumberFor
1 the private, 1,
◆ January noncom-
2018
mercial use of one individual user of the website. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests.
 PRACTICE GUIDELINES

result does not exclude pulmonary TB, nor does or a nucleic acid amplification test (NAAT) who
a positive result confirm it. If extrapulmonary have been treated previously for TB; who were
TB is suspected, specimens should be collected born in or lived for at least one year in a foreign
from those sites for mycobacterial culture; a pos- country with an intermediate incidence of TB
itive result can be reasonable evidence of disease, or high prevalence of multidrug-resistant TB;
but a negative result does not exclude disease who are in contact with persons with multidrug-
because of the high false-negative rate. resistant TB; or who have human immunodefi-
Rapid molecular drug susceptibility testing ciency virus infection.
of respiratory specimens for rifampin alone or When there is a positive result on mycobac-
combined with isoniazid should be performed terial culture, one culture isolate should be pro-
in persons with positive results on an AFB smear vided to a regional laboratory for genotyping.

TABLE 1

Summary of Recommendations for LTBI Testing

Group* Testing strategy Considerations

Likely to be infected Adults Prevalence of bacillus

High risk of Acceptable: IGRA or TST Calmette-Guérin
progression vaccination
Consider dual testing, in which a positive result
(TST ≥ 5 mM) from either would be considered positive† Expertise of staff or
laboratory
Children ≤ 5 years
Test availability
Preferred: TST
Patient and staff
Acceptable: IGRA or TST perceptions
Consider dual testing, in which a positive result Programmatic
from either would be considered positive† concerns
Likely to be infected Preferred: IGRA where available
Low to intermediate Acceptable: IGRA or TST
risk of progression
(TST ≥ 10 mM)

Unlikely to be infected Testing for LTBI is not recommended

(TST > 15 mM) If necessary:
Preferred: IGRA where available
Acceptable: IGRA or TST
For serial testing
Acceptable: IGRA or TST
Consider repeat or dual testing, in which a
negative result from either would be considered
negative‡

IGRA = interferon-gamma release assay; LTBI = latent tuberculosis infection; TST = tuberculin skin test.
*—These groups are determined on the risk for infection with tuberculosis and risk of progression and benefit of therapy.
†—Performing a second diagnostic test when the initial test is negative is a strategy to increase sensitivity. This may
reduce specificity, but the panel decided that this is an acceptable trade-off in situations in which the consequences
of missing LTBI (i.e., not treating persons who may benefit from therapy) exceed the consequences of inappropriate
therapy (i.e., hepatotoxicity).
‡—Performing a confirmatory test following an initial positive result is based on the evidence that false-positive results
are common among persons who are unlikely to be infected with Mycobacterium tuberculosis and the committee’s
presumption that performing a second test in those patients whose initial test result was positive will help identify initial
false-positive results.
Adapted with permission from Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infec-
tious Diseases Society of America/Centers for Disease Control and Prevention clinical practice guidelines: diagnosis of
tuberculosis in adults and children. Clin Infect Dis. 2017;64(2):114.

January 1, 2018 ◆ Volume 97, Number 1 www.aafp.org/afp American Family Physician 57

 PRACTICE GUIDELINES

Conditional. If TB is suspected, liquid and on fluid specimens (e.g., pleural or cerebrospinal

solid mycobacterial cultures can both be per- fluid). An AFB smear and NAAT are also recom-
formed on respiratory specimens, rather than mended; a positive result on either can be rea-
just one or the other, for each specimen. sonable evidence of disease, but a negative result
If pulmonary TB is suspected, NAAT is rec- on either cannot exclude disease, because of the
ommended for the first respiratory specimen; high false-negative rate. Histologic examination
a negative result in a patient who had a positive should be performed, with positive and nega-
result on AFB smear makes TB improbable. A tive results evaluated based on each individual
positive result on NAAT in a patient who had situation.
a negative result on AFB smear, but in whom In persons with suspected pleural, peritoneal,
there is a moderate to high level of suspicion for or pericardial TB, or tuberculous meningitis,
TB, can be considered reasonable evidence of measurement of adenosine deaminase is recom-
TB. However, a negative NAAT result does not mended, with measurement of free interferon
exclude pulmonary TB. If pulmonary TB is sus- gamma also performed in those with suspected
pected in a child, mycobacterial culture of respi- pleural or peritoneal TB.
ratory specimens is recommended. Guideline source: American Thoracic Society,
For adults with suspected pulmonary TB who Infectious Diseases Society of America, and Centers
cannot provide sputum or whose sputum was for Disease Control and Prevention
negative on AFB smear, sputum induction is rec- Evidence rating system used? Yes
ommended over flexible bronchoscopy for ini- Systematic literature search described? Yes
tial sampling. When sputum induction does not Guideline developed by participants without rele-
work, flexible bronchoscopy is recommended vant financial ties to industry? No
over no sampling. When adults with suspected Recommendations based on patient-oriented out-
pulmonary TB undergo bronchoscopy, spu- comes? Yes
tum samples should be collected to use in AFB Published source: Clin Infect Dis. January 15,
smears and mycobacterial cultures. 2017;64(2):111-115
For adults with suspected miliary TB, but in Available at: https://academic.oup.com/cid/
whom sputum cannot be induced or whose spu- article-lookup/doi/10.1093/cid/ciw778
tum was negative on AFB smear, flexible bron- Lisa Hauk
choscopy is preferred to no sampling if no other AFP Senior Associate Editor ■
lesions can be accessed.
In persons with suspected extrapulmonary TB,
cell counts and chemistries should be performed

58  American Family Physician www.aafp.org/afp Volume 97, Number 1 ◆ January 1, 2018