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A
Latent Tuberculosis Infection: 
A Guide for Primary 
Health Care Providers
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1
Latent  
tubercuLosis 
infection:
a Guide for  
Primary  
HeaLtH care 
Providers
U.S. Department of Health and Human Services
Centers for Disease Control and Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, 
and TB Prevention
Division of Tuberculosis Elimination
Atlanta, Georgia 
Developed in partnership with the New Jersey 
Medical School Global Tuberculosis Institute
2013
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Table of ConTenTs 
4 
List of Abbreviations
5 
Introduction
6 
Targeted Testing for Tuberculosis
Identifying Persons at Risk for Developing TB Disease
8 
Diagnosis of Latent TB Infection (LTBI)
Table 1: Differentiating Between LTBI and TB Disease .......................8  
Tests for TB Infection ........................................................................9
Tuberculin Skin Test ..........................................................................9
Classification of Tuberculin Skin Test Reactions .................................9
Interferon-Gamma Release Assays .................................................10
Special Considerations in Testing for TB Infection ...........................12
Figure 1: Two-Step TST Testing .......................................................13
Other Diagnostic Considerations ....................................................14
16 
Treatment of Latent TB Infection 
Treatment Regimens ......................................................................16
Table 2: Choosing the Most Effective Treatment Regimen ..............18
Special Considerations in the Treatment of LTBI ..............................19
Adverse Effects of Drugs Used to Treat LTBI ....................................21  
Patient Monitoring and Education during Treatment ......................23
Assessing Adherence .....................................................................24
Techniques to Improve Adherence .................................................25  
Post-Treatment Follow-Up ..............................................................26
27 
Appendix A: Sample TB Risk Assessment Tool
28 
Appendix B: Identifying Persons from High-Risk Countries
29 
Appendix C: Administration and Measurement of the TST
31 
Appendix D: Certain situations where results from both TST 
and IGRA may be useful 
32 
Appendix E: Sample TST and Treatment Documentation Forms
34 
Resources
36 
References
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4
lisT of abbreviaTions
AFB 
acid-fast bacilli
ART 
antiretroviral therapy
AIDS 
acquired immune deficiency syndrome
ALT  
alanine aminotransferase
AST 
aspartate aminotransferase
ATS 
American Thoracic Society
BCG 
bacille Calmette-Guérin
CDC 
Centers for Disease Control and Prevention
DOT 
directly observed therapy
FDA 
Food and Drug Administration
HIV 
human immunodeficiency virus
IGRA 
interferon-gamma release assay
IFN-g 
interferon-gamma 
INH 
isoniazid
LTBI 
latent TB infection
MDR TB 
multidrug-resistant tuberculosis
MMWR 
Morbidity and Mortality Weekly Report
PPD 
purified protein derivative
QFT-GIT 
QuantiFERON®-TB Gold In-tube 
RIF 
rifampin
RPT 
rifapentine
TB 
tuberculosis
TNF-a  
tumor necrosis factor-alpha
TST 
tuberculin skin test
WHO 
World Health Organization
4
5
inTroduCTion
This guide is intended for primary care providers who care for 
individuals and populations who may be at risk for infection with 
Mycobacterium tuberculosis. Latent tuberculosis infection (LTBI) is 
the presence of Mycobacterium tuberculosis in the body without 
signs and symptoms, or radiographic or bacteriologic evidence of 
tuberculosis (TB) disease. 
Approximately one-third of the world’s population is infected with 
M. tuberculosis. It is estimated that more than 11 million people 
in the United States have LTBI, which is about 4% of the total 
population. While not everyone with LTBI will develop TB disease, 
about 5 – 10% of infected people will develop TB disease if not 
treated. This equates to approximately 550,000 to 1,100,000 people 
who will develop TB at some point in their life, unless they receive 
adequate treatment for LTBI. Identifying and treating those at 
highest risk for TB disease will help move toward elimination of the 
disease. Primary care providers play a key role in achieving the goal 
of TB elimination because of their access to high-risk populations.
Guidelines for testing and treating LTBI were released by the Centers 
for Disease Control and Prevention (CDC) and the American Thoracic 
Society (ATS). They can be found in the June 9, 2000 issue of 
Morbidity and Mortality Weekly Report (MMWR), entitled Targeted 
Tuberculin Testing and Treatment of Latent Tuberculosis Infection. 
More recently, recommendations for the use of interferon-gamma 
release assays (IGRAs) were released in the June 25, 2010 issue of 
Morbidity and Mortality Weekly Report (MMWR), entitled Updated 
Guidelines for Using Interferon Gamma Release Assays to Detect 
Mycobacterium Tuberculosis Infection. In addition, recommendations 
for a new regimen for the treatment of LTBI were introduced. They 
can be found in the December 9, 2011 issue of Morbidity and 
Mortality Weekly Report (MMWR), entitled Recommendations for 
Use of an Isoniazid-Rifapentine Regimen with Direct Observation to 
Treat Latent Mycobacterium tuberculosis Infection.
This document is not meant to be used as a substitute for the 
guidelines, but rather as a ready and useful reference that 
highlights the main points of those guidelines.
6
TargeTed TesTing for 
TuberCulosis
Targeted testing is an essential TB prevention and control strategy 
that is used to identify, evaluate, and treat persons who are at 
high risk for latent tuberculosis infection (LTBI) or at high risk for 
developing TB disease once infected with M. tuberculosis. Identifying 
persons with LTBI is important to the goal of TB control and 
elimination because treatment of LTBI can prevent infected persons 
from developing TB disease and stop the further spread of TB. All 
testing activities should be accompanied by a plan for appropriate 
follow-up medical evaluation and treatment. Necessary medical 
evaluation and treatment resources need to be identified before 
testing activities begin. Unfocused population-based testing is not 
cost-effective or useful and leads to unnecessary treatment. TB 
testing activities should be conducted only among high-risk groups, 
with the intent to treat if LTBI is detected. Once TB disease has been 
excluded, treatment of LTBI should be offered to patients regardless 
of their age, unless medically contraindicated. 
However, there may be instances in which health care providers are 
asked to test individuals who are not necessarily regarded as high 
risk (e.g., daycare center workers, teachers, and U.S.-born students). 
A few simple questions will help health care providers assess a 
patient’s risk for LTBI. Appendix A (p. 27) contains a sample risk 
assessment tool.
Currently, there are 2 testing methods available for the detection of 
M. tuberculosis infection in the United States:
• Mantoux tuberculin skin test (TST) 
• Interferon-gamma release assays (IGRAs)
Two U.S. Food and Drug Administration (FDA) approved IGRAs are 
commercially available in the United States:
• QuantiFERON
®
-TB Gold-in-Tube test (QFT-GIT)
• T-SPOT
®
.TB test
6
7
identifyinG Persons at risk for deveLoPinG tb disease
Generally, persons at risk for developing TB disease fall into 2 broad 
categories:
• Those who have an increased likelihood of exposure to persons 
with TB disease
• Those with clinical conditions or other factors associated with an 
increased risk of progression from LTBI to TB disease
Persons at risk for exposure to persons with TB disease include the 
following:
• Known close contacts of a person with infectious TB disease
• Persons who have immigrated from TB-endemic regions of the 
world (see Appendix B, p. 28)
• Persons who work or reside in facilities or institutions with people 
who are at high risk for TB, such as hospitals that care for TB 
patients, homeless shelters, correctional facilities, nursing homes, 
or residential facilities for patients with HIV infection/AIDS
Also at risk are those with certain conditions and other factors 
associated with progression from LTBI to TB disease. These conditions 
and factors include the following:
• HIV infection
• Injection drug use
• Radiographic evidence of prior healed TB
• Low body weight (10% below ideal) 
• Other medical conditions such as - 
– silicosis 
– diabetes mellitus
– chronic renal failure or on hemodialysis 
– gastrectomy
– jejunoileal bypass 
– solid organ transplant 
– head and neck cancer 
– conditions that require prolonged use of corticosteroids or other 
immunosuppressive agents such as TNF-a antagonists
• Recent TST converters (that is, persons with baseline testing results 
who have an increase of 10 mm or more in the size of the TST 
reaction within a 2-year period)
• Infants and children under the age of 5 who have a positive TB 
test result
Of note, the risk of progression is greatest in the first 1 or 2 years after infection.
8
tabLe 1:
differentiating between Latent tb infection and tb disease
LTBI
•  No symptoms or physical findings 
suggestive of TB disease. 
•  TST or IGRA result usually positive.
•  Chest radiograph is typically 
normal.
•  If done, respiratory specimens are 
smear and culture negative.
•  Cannot spread TB bacteria to 
others.
•  Should consider treatment for LTBI 
to prevent TB disease.
TB Disease
•  Symptoms may include one or 
more of the following: fever, 
cough, chest pain, weight loss, 
night sweats, hemoptysis, fatigue, 
and decreased appetite.
•  TST or IGRA result usually positive.
•  Chest radiograph is usually 
abnormal. However, may 
be normal in persons with 
advanced immunosuppression or 
extrapulmonary disease.
•  Respiratory specimens are usually 
smear or culture positive. However, 
may be negative in persons with 
extrapulmonary disease or minimal 
or early pulmonary disease.
•  May spread TB bacteria to others.
•  Needs treatment for TB disease.
8
diagnosis of laTenT Tb infeCTion 
The diagnosis of LTBI is based on information gathered from the 
medical history, TST or IGRA result, chest radiograph, physical 
examination, and in certain circumstances, sputum examinations. 
The presence of TB disease must be excluded before treatment for 
LTBI is initiated because failure to do so may result in inadequate 
treatment and development of drug resistance (see Table 1).
CDC discourages use of diagnostic tests for LTBI among individuals 
and populations at low risk for infection with M. tuberculosis. 
Despite CDC recommendations to the contrary, testing is sometimes 
done to meet administrative or legal requirements for groups who 
are not considered to have an increased possibility of infection in 
the absence of other factors cited above, such as persons meeting 
entrance requirements for certain schools and workplaces.
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