TB Facts for Health Care Workers
Identification of Persons with Latent TB Infection
and TB Disease
Identifying Latent TB Infection (LTBI)
A person exposed to an individual with infectious TB or who has
other risk factors for TB as noted above should be given a Mantoux
tuberculin skin test (TST) or the QuantiFERON®-TB Gold
The Mantoux Tuberculin Skin Test
The Mantoux tuberculin skin test is the intradermal injection of
purified protein derivative (PPD) of killed tubercle bacilli, usually
on the inner forearm. The site is examined by a trained health care
worker 48 to 72 hours after injection for induration (palpable swelling).
The diameter of induration is measured and recorded; erythema or
bruising is disregarded.
The criteria endorsed by the American Thoracic Society (ATS) and
the Centers for Disease Control and Prevention (CDC) for a positive
tuberculin skin-test result (Table 1) are intended to increase the
likelihood that persons at high risk for TB will be candidates for
treatment of LTBI and that persons having tuberculin reactions not
caused by M. tuberculosis will not receive unnecessary diagnostic
evaluation or treatment.
For each of the risk groups listed in Table 1, reactions below
the cutoff point are considered negative. A negative TST result
does not absolutely rule out LTBI, especially in persons with TB-like
symptoms, HIV infection, or AIDS. Also, it takes up to 8 weeks from
the time of exposure for a person to react to tuberculin; thus,
the initial TST result of an infected contact may be falsely negative.
Therefore, a repeat TST 8–10 weeks postexposure is warranted.
Some persons with both HIV and latent TB infections may have false-negative
TST reactions (anergy). Anergy refers to the inability to react
to a skin-test antigen even though the person is infected with the
organism being tested. Several delayed-type hypersensitivity (DTH)
antigens (such as tetanus toxoid, mumps, or Candida) administered
by the Mantoux technique have been used in an attempt to determine
anergy status. Recent CDC recommendations, however, note several
factors that limit the usefulness of anergy skin testing. These
include problems with standardization and reproducibility, the low
risk for TB associated with a diagnosis of anergy, and the lack
of apparent benefit of LTBI treatment for groups of anergic HIV-infected
persons. Therefore, the use of anergy testing in conjunction with
PPD testing is no longer routinely recommended for TB testing programs
in the United States.
Persons with LTBI should be evaluated for HIV risk behaviors and
offered counseling and HIV-antibody testing especially if such risk
behaviors are present.
Table 1: Summary of interpretation
of tuberculin skin-test (TST) results
An induration of >5 mm is classified as
positive in the following groups:
- Persons who have HIV infection;
- Persons who have had recent close contact with persons
who have TB;
- Patients who have had organ transplants, and other immunosuppressed
patients (receiving the equivalent of >15 mg/day
of prednisone for >1 month);
- Persons with fibrotic changes on chest radiograph consistent
with old TB;
- Persons receiving specialized treatment for rheumatoid
arthritis or Crohn’s disease.
An induration of >10 mm is classified as
positive in all persons who do not meet any of the above criteria,
but belong to one or more of the following groups having high
risk for TB:
- Foreign-born persons recently arrived (e.g., within the
last 5 years) from areas having a high prevalence or incidence
- Persons who inject illicit drugs;
- Residents and employees of high-risk congregate settings:
prisons and jails, nursing homes and other long-term facilities
for the elderly, health-care facilities (including some
residential mental health facilities), and homeless shelters;
- Mycobacteriology laboratory personnel;
- Persons who have other medical conditions that have been
reported to increase the risk for progressing from LTBI
to TB -- these medical conditions include diabetes mellitus,
silicosis, prolonged corticosteroid therapy and other immunosuppressive
therapy, cancer of the head and neck, hematologic and reticuloendothelial
diseases, end-stage renal disease, intestinal bypass or
gastrectomy, chronic malabsorption syndromes, or weight
loss of >10% below ideal body weight;
- Children <4 years of age, or children and adolescents
exposed to adults in high-risk categories.
An induration of >15 mm is classified as
positive in persons who do not meet any of the above criteria.
Quantiferon®-TB Gold Test (QFT)
The Quantiferon®-TB Gold test (QFT-G) is a blood test
that measures a person’s immune reactivity to M. tuberculosis.
Blood specimens are mixed with antigens and incubated for 16–24
hours. In a person with LTBI, the blood cells recognize the tuberculin
antigen and release interferon-gamma (IFN-γ); results are based
on the proportion of IFN-γ released. The first generation QFT
(Quantiferon®-TB test) was approved by the U.S. Food
and Drug Administration (FDA) in 2001. The second generation test
(Quantiferon®-TB Gold test) was approved by the FDA in
- Requires a single patient visit
- Does not cause booster phenomenon
- Less subject to reader bias than TST
- Blood sample must be processed in 12 hours
QFT-G is recommended for
- Initial and serial testing for those at increased risk for LTBI
CDC discourages use of diagnostic tests for LTBI among populations
at low risk for infection with M. tuberculosis. However,
initial testing is occasionally performed among certain population
groups for surveillance purposes or where cases of infectious TB
disease might result in extensive transmission to highly susceptible
populations, including the following:
- Initial and serial testing of persons who are at low
risk for LTBI, but whose future activity places them at increased
risk of exposure;
- Testing of those who are not considered to have an increased
possibility of infection, such as persons meeting entrance requirements
for certain schools and workplaces.
There are limited data regarding the use of
- Screening of pregnant women, children under the age of 17, or
persons with clinical conditions that increase the risk
of progression to disease
QFT-G is not currently recommended for
- Confirmation of TST results
- Diagnosis of M. avium-complex disease
Please refer to the CDC website for the most current information
on the use of QFT-G: www.cdc.gov/tb.
The Bacille Calmette-Guérin (BCG) Vaccine
The Bacille Calmette-Guérin (BCG) vaccine is a live vaccine derived
from a strain of Mycobacterium bovis that was attenuated
by Calmette and Guérin at the Pasteur Institute in Lille, France.
An early version of BCG was first administered to humans in 1921.
Since that time, many different strains have been derived and are
used today throughout the world. BCG vaccination is not generally
recommended in the United
States because of the low risk of infection
with M. tuberculosis, the variable effectiveness of
the BCG vaccine against adult pulmonary TB, and the vaccine’s
interference with the ability to interpret tuberculin reactivity.
Many foreign countries still use BCG as an appropriate part of
their TB control programs for infants. In persons vaccinated with
BCG, sensitivity to tuberculin is highly variable, depending upon
the strain of BCG used, the group vaccinated, and age at vaccination.
Neither the TST nor QFT-G is contraindicated for persons who have
been vaccinated with BCG. The presence or size of a postvaccination
TST reaction does not predict whether BCG will provide any protection
against TB disease. The size of a TST reaction in a BCG-vaccinated
person is not a factor in determining whether the reaction is caused
by M. tuberculosis infection or by the prior BCG vaccination.
The TST results are used to support or exclude the diagnosis of
LTBI. TST results in persons vaccinated with BCG should be interpreted
using the same criteria for those not BCG vaccinated. Such persons
should be evaluated for isoniazid to treat LTBI after disease has
been ruled out.
Identifying TB Disease
If the skin-test result or QFT-G is positive, or if symptoms suggestive
of TB are present (e.g., productive and prolonged cough, fever,
chills, loss of appetite, weight loss, fatigue, or night sweats),
a chest radiograph should be obtained to determine if active pulmonary
TB is present. The chest radiograph may also be used to detect the
presence of fibrotic lesions suggestive of old, healed TB or silicosis.
Acid-fast bacilli (AFB) smears and cultures should be performed
on sputum specimens of all persons who have symptoms of TB or whose
chest radiograph suggests TB. A positive AFB smear is an indication
for beginning treatment for TB. However, a positive AFB smear may
also indicate the presence of nontuberculous mycobacteria. A positive
culture for M. tuberculosis is the only definitive proof
of TB disease.
Health care providers of HIV-infected persons should be aware of
atypical patterns of TB disease in these persons. Extrapulmonary
TB is more common among HIV-infected persons. Also, pulmonary TB
may present in an unusual manner (e.g., in the lymph nodes or in
the lower part of the lungs).
All persons with LTBI or TB disease should routinely be offered
HIV counseling, testing, and referral because medical management
may be altered in the presence of HIV infection.
|Maintain a high index of suspicion for TB in persons with
undiagnosed pulmonary disease, especially in persons who are