Clinical Overview of Latent Tuberculosis Infection

Key points

  • People with latent TB infection are infected with TB bacteria, but they do not have TB disease.
  • However, if these bacteria become active and multiply, latent TB infection can develop into TB disease.
  • Treating people with latent TB infection substantially reduces the risk that latent TB infection will progress to TB disease.
A health care provider talks to a smiling patient.

Overview

Not everyone infected with TB bacteria becomes sick. As a result, two TB-related conditions exist: latent TB infection (also called inactive TB) and TB disease.

People with latent TB infection:

  • Have a small number of TB bacteria in their body that are alive but inactive
  • Cannot spread TB bacteria to others
  • Do not feel sick, but may become sick if the bacteria in their bodies become active
  • Usually have a positive TB blood test or TB skin test results indicating TB infection
  • Have typically normal chest radiographs
  • Have negative sputum smears and cultures
  • Should consider treatment for latent TB infection to prevent TB disease
  • Do not require respiratory isolation

Eliminating TB in the United States requires testing and treatment of latent TB infection

CDC estimates that up to 13 million people in the United States have latent TB infection. While not everyone with latent TB infection will develop TB disease, without treatment about 5%–10% of infected people will develop TB disease over their lifetimes.

People with latent TB infection are at risk for TB disease.‎

Progression from untreated latent TB infection to TB disease accounts for approximately 80% of U.S. TB cases.

Finding and treating people with latent TB infection is essential for controlling and eliminating TB disease in the United States. Treatment for latent TB infection is effective for preventing TB disease.

For Everyone: About Inactive Tuberculosis

Cause

TB infection occurs when a person inhales tubercle bacilli that reach the alveoli of the lungs.

While most bacilli are destroyed or inhibited, a small number may enter the bloodstream and spread throughout the body. The tubercle bacilli may reach any part of the body, including areas where TB disease is most likely to develop such as the:

  • Lymph nodes,
  • Lungs,
  • Kidneys,
  • Brain, and
  • Bone.

Within 2 to 8 weeks, special immune cells called macrophages ingest and surround the tubercle bacilli. The cells form a barrier shell called a granuloma that keeps the bacilli contained and under control. This condition is known as latent TB infection.

Risk factors

People at increased risk for TB infection should be tested.‎

CDC and the U.S. Preventive Services Task Force recommend testing people at increased risk for TB infection. Testing for TB infection should be a routine and integral part of health care for patients with increased risk for TB. Frequency of testing will depend on a person's risk for TB.
Clinical Testing and Diagnosis

People at risk for TB fall into two broad categories:

  • People who are at high risk of exposure to or infection with TB bacteria
  • People who are at high risk of developing TB disease once infected with TB bacteria

  • Contacts of people known or presumed to have infectious TB disease
  • People who were born in or who frequently travel to countries where TB disease is common
  • People who currently live or used to live in large group settings where TB is more common, such as homeless shelters, correctional facilities, or nursing homes
  • Employees of high-risk congregate settings
  • Health care workers who serve patients with TB disease
  • Populations defined locally as having an increased incidence of latent TB infection or TB disease, possibly including medically underserved populations, low-income populations, or persons with alcohol use or substance use disorders
  • Infants, children, and adolescents exposed to adults who are at increased risk for latent TB infection or TB disease

  • People with HIV
  • Children younger than 5 years of age
  • People recently infected with TB bacteria (within the last 2 years)
  • People with a history of untreated or inadequately treated TB disease
  • People who are receiving immunosuppressive therapy such as tumor necrosis factor-alpha (TNF) antagonists, systemic corticosteroids equivalent to/greater than 15 mg of prednisone per day, or immunosuppressive drug therapy following organ transplantation
  • People with silicosis; chronic renal failure; leukemia; or cancer of the head, neck, or lung
  • People with diabetes mellitus
  • People who have had a gastrectomy or jejunoileal bypass
  • People with low body weight (<90% of ideal body weight)
  • People who use substances (such as injection drug use)
  • Populations defined locally as having an increased incidence of TB disease, including medically underserved and low-income populations
Keep Reading: Tuberculosis Risk Factors

How it spreads

People with latent TB infection cannot spread TB bacteria to others.

However, if these bacteria become active and multiply, latent TB infection can develop into TB disease. Once active, TB can be spread from person to person through the air.

Prevalence

Latent TB infection prevalence data is critical in order to track the United States’ progress in testing and treating persons with latent TB infection. CDC estimates that up to 13 million people in the United States have latent TB infection.

TB disease is a nationally notifiable disease; however, latent TB infection is not reported to CDC. Some states and localities have developed legal reporting requirements for latent TB infection as a tool to prevent TB disease.

CDC currently relies on national prevalence estimates and is exploring systems and methods to determine the best ways to measure prevalence of latent TB infection in the United States.

Keep Reading: Latent TB Infection in the United States - Published Estimates

Testing and diagnosis

Testing for TB infection is a routine and integral part of health care for patients with increased risk for TB. Frequency of testing depends on a person's risk factors. This could range from one-time only testing among persons at low risk for future TB exposure to annual testing among those at continued risk of exposure.

There are two types of tests that can determine if a person has been infected with TB bacteria:

TB blood tests (sometimes called IGRAs) measure the immune response to TB proteins in whole blood to determine if a person is infected with TB bacteria.

For TB blood tests, specimens are mixed with peptides that simulate antigens derived from TB bacteria and with controls. In most people infected with TB bacteria, the white blood cells recognize the simulated antigens and release interferon-gamma (IFN-γ). The tests measure the level of IFN-γ response.

The U.S. Food and Drug Administration (FDA) has approved these two TB blood tests that are commercially available in the United States:

  • QuantiFERON®-TB Gold Plus (QFT-Plus)
  • T-SPOT®.TB test (T-Spot)
Keep Reading: Clinical Testing Guidance for Tuberculosis: Interferon Gamma Release Assay

The TB skin test is also called the Mantoux tuberculin skin test (TST) or PPD. With a TB skin test, a health care provider injects a small, premeasured amount of sterile tuberculin PPD solution into the skin on the palm side of the forearm. This is sometimes called the Mantoux TST method. PPD stands for purified protein derivative of tuberculin solution, which comes in a single standard concentration. It is the only kind of TB skin test solution that is FDA-approved for this test method.

After 48–72 hours, the skin test reaction must be examined by a trained health care worker. The health care worker measures the induration (firm swelling) where the tuberculin was injected to determine if the reaction to the test is positive or negative.

Keep Reading: Clinical Testing Guidance for Tuberculosis: Tuberculin Skin Test

Using either a TB blood test or a TB skin test is acceptable medical and public health practice.

Health care providers are encouraged to use newer TB blood tests to detect latent TB infection. TB skin tests are an acceptable alternative in situations where a TB blood test is not available, is too costly, or is too burdensome.

The bacille Calmette-Guérin (BCG) TB vaccine can cause a false positive TB skin test result. Unlike the TB skin test, TB blood tests are not affected by BCG vaccination.

Routine testing with both TB blood and skin tests is not recommended.

Consider these factors when determining which test to use.

TB blood test is the preferred method of testing for:

  • People who have received the BCG vaccine
  • People who might be less likely to return for TB skin test reading and interpretation

TB skin test is the preferred TB test for:

  • Children under the age of five.
  • Some experts use TB blood tests in younger children. Health care providers may choose to consult the American Academy of Pediatrics (AAP) guidance1 on the use of TB blood tests in children.

Keep in mind‎

TB blood tests or skin tests should not be performed on people who have written documentation of a previous positive TB test results (TB blood test or TB skin test) or treatment for TB disease.

A positive reaction to a TB blood test or TB skin test is interpreted as TB infection. More tests, such as a chest radiograph, are needed to rule out TB disease.

A diagnosis of latent TB infection is made if a person has a positive TB blood test or TB skin test result and a medical exam does not indicate TB disease. The diagnosis is based on information gathered from:

  • Medical history,
  • TB blood test or TB skin test,
  • Chest radiograph,
  • Physical examination, and
  • Sputum examination (in certain circumstances).

TB disease must be excluded before initiating treatment for latent TB infection. Failure to do so may result in treatment failure and development of drug resistance.

Keep Reading: Diagnosing Tuberculosis

Treatment and recovery

People with latent TB infection should be treated to prevent the development of TB disease. Progression from untreated latent TB infection to TB disease accounts for approximately 80% of U.S. TB disease cases. Treating latent TB infection is 90% effective in preventing the development of TB disease.

There are several standard treatment regimens for the treatment of latent TB infection. Regimens use the drugs isoniazid (H), rifapentine (P), and/or rifampin (R).

CDC and the National Tuberculosis Coalition of America preferentially recommend short-course, rifamycin-based, 3- or 4-month latent TB infection treatment regimens over 6- or 9-month isoniazid monotherapy. Short-course latent TB infection treatments are effective, safe, and have higher completion rates than treatment regimens.

  • Three months of once-weekly isoniazid plus rifapentine (3HP)
  • Four months of daily rifampin (4R)
  • Three months of daily isoniazid plus rifampin (3HR)

  • 6 to 9 months of isoniazid monotherapy (6H/9H) are alternative, effective latent TB infection treatment regimens if a short-course treatment regimen is not an option.
  • Although effective, 6H and 9H have higher serious toxicity risk and lower treatment completion rates than rifamycin-based short-course treatment regimens.

Treatment must be modified if the patient is a contact of an individual with drug-resistant TB disease. Consultation with a TB expert is advised if the likely source of TB infection has drug-resistant TB disease.

Health care providers should choose the appropriate treatment regimen based on:

  • Drug-susceptibility results of the presumed source case (if known), and
  • Coexisting medical conditions, and
  • Potential for drug-drug interactions.

Local and state TB programs can answer questions and provide additional information on local practices, resources, and materials to help health care providers treat latent TB infection.

For patients who need an alternative regimen because drug resistance is suspected or because of drug allergies or drug-drug interactions, consultation with a TB expert is recommended.

Keep Reading: Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020

Resources

Latent Tuberculosis Infection: A Guide for Primary Health Care Providers
Guide for primary care providers with latent TB infection diagnosis and treatment information. 
Latent Tuberculosis Infection Testing and Treatment: Summary of U.S. Recommendations
Summary of U.S. recommendations for LTBI testing and treatment
Latent TB Infection Resource Hub
This resource hub is a one-stop-shop for latent TB infection materials.
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Content Source:
Division of Tuberculosis Elimination ; National Center for HIV, Viral Hepatitis, STD, and Tuberculosis Prevention; Centers for Disease Control and Prevention
  1. 2024. "Tuberculosis", Red Book: 2024–2027 Report of the Committee on Infectious Diseases, Committee on Infectious Diseases, American Academy of Pediatrics, David W. Kimberlin, MD, FAAP, Ritu Banerjee, MD, PhD, FAAP, Elizabeth D. Barnett, MD, FAAP, Ruth Lynfield, MD, FAAP, Mark H. Sawyer, MD, FAAP. Available from: https://publications.aap.org/redbook/book/755/chapter/14083107/Tuberculosis