Introduction: Who Should Undergo Diagnostics for Latent Tuberculosis

Not everyone needs to be tested for latent tuberculosis infection. Testing is most important for people who have a higher chance of having been exposed to tuberculosis bacteria or who are at greater risk of the infection becoming active disease. If you have recently spent time with someone who has active tuberculosis, especially in close quarters like a household or workplace, you should consider getting tested. People who work or live in settings where tuberculosis can spread more easily—such as hospitals, nursing homes, homeless shelters, jails, or refugee camps—should also seek testing.^[1]

It is also advisable to undergo diagnostics if you were born in or have lived in regions where tuberculosis is common, including parts of Latin America, the Caribbean, Africa, Asia, and Eastern Europe. Individuals with weakened immune systems face a much higher risk of latent tuberculosis progressing to active disease. This includes people living with HIV, those undergoing chemotherapy, organ transplant recipients, people with diabetes or kidney disease, and anyone taking medications that suppress the immune system.^[1][3]

Young children under one year of age and elderly individuals are also at increased risk, as their immune systems may not be strong enough to keep the bacteria dormant. Because latent tuberculosis has no symptoms, you won’t know you have it unless you get tested. That’s why testing is crucial for people in these higher-risk groups—it helps catch the infection early, before it has a chance to turn into active disease that could harm you and spread to others.^[7]

Diagnostic Methods for Identifying Latent Tuberculosis Infection

Diagnosing latent tuberculosis infection involves a combination of tests that help determine whether tuberculosis bacteria are present in your body, even though you have no symptoms. The process typically begins with either a skin test or a blood test, followed by additional examinations to rule out active disease.

Tuberculin Skin Testing

The tuberculin skin test, also called the Mantoux test, is one of the most common methods used to detect latent TB infection. During this test, a small amount of a substance called tuberculin is injected just under the skin of your forearm. You then need to return to the clinic after 48 to 72 hours so a healthcare provider can examine your arm. If you have been infected with TB bacteria, your immune system will react to the tuberculin, causing a raised, firm bump at the injection site.^[2]

The size of this bump is measured in millimeters. The interpretation of the result depends on your risk factors. For example, a smaller reaction might be considered positive if you have HIV or have been in close contact with someone with active TB. A larger reaction is typically required to be considered positive if you have no known risk factors. This test does not tell you whether the infection is active or latent—it simply shows whether your immune system has encountered TB bacteria at some point.^[2][9]

One thing to be aware of is that if you have received the BCG vaccine (a vaccine sometimes given in countries where tuberculosis is common), you might have a positive skin test result even if you don’t have TB infection. The BCG vaccine can cause a reaction similar to a TB infection. However, this should not prevent you from being tested or treated if needed, because the BCG vaccine only protects children for a few years and does not prevent latent or active TB in adults.^[4][5]

Blood Tests for TB Infection

A newer type of test, called an interferon-gamma release assay or IGRA, is a blood-based test that measures how your immune system responds to TB bacteria. A sample of your blood is taken and sent to a laboratory, where it is mixed with proteins from TB bacteria. If your immune cells have been exposed to TB before, they will release a substance called interferon-gamma, which the test can detect.^[3]

One advantage of the IGRA test is that it is not affected by the BCG vaccine, so it may be more accurate for people who have been vaccinated. It also requires only one visit to the clinic, unlike the skin test, which requires a follow-up appointment to read the results. Both the skin test and the blood test are effective at detecting latent TB infection, and your healthcare provider will choose the best test based on your age, medical history, and other factors.^[3][12]

Chest X-Ray and Additional Tests

If either the skin test or blood test comes back positive, your healthcare provider will want to make sure you do not have active tuberculosis disease. The most important next step is usually a chest X-ray, which creates an image of your lungs. In people with latent TB infection, the chest X-ray typically looks normal because the bacteria are not actively causing damage. However, if there are signs of disease—such as spots, shadows, or other abnormalities—it could indicate active TB, which requires different and more intensive treatment.^[7][9]

Your doctor may also ask about any symptoms you might have, such as a persistent cough, fever, night sweats, weight loss, or fatigue. These symptoms are signs of active disease, not latent infection. If you have no symptoms and a normal chest X-ray, the diagnosis of latent TB infection is confirmed. In some cases, doctors may also test samples of sputum (mucus coughed up from the lungs) to look for TB bacteria, but this is typically only done if active disease is suspected.^[9]

Distinguishing Latent TB from Active TB

One of the most important aspects of diagnosing latent tuberculosis is making sure it is not confused with active TB disease. People with latent TB have no symptoms, feel completely well, and cannot spread the infection to others. Their chest X-rays are normal, and tests of their sputum do not show any TB bacteria. In contrast, people with active TB often feel sick, may have a cough that lasts more than two weeks, and can spread the disease to others if it is in their lungs.^[9]

The tests used for diagnosis help your healthcare provider distinguish between these two states. Latent infection is identified by a positive skin test or blood test combined with the absence of symptoms and a normal chest X-ray. Active disease is identified by symptoms, abnormal chest X-rays, and the presence of bacteria in sputum or other body fluids.^[9]

Diagnostics for Clinical Trial Qualification

Clinical trials are research studies that test new treatments or prevention strategies for diseases, including latent tuberculosis infection. To participate in a clinical trial, patients must meet specific criteria, and diagnostic tests are used to determine whether someone is eligible.

For latent TB clinical trials, the first requirement is typically confirmation that a person has latent TB infection. This is done using the same diagnostic methods described earlier: a positive tuberculin skin test or a positive interferon-gamma release assay (IGRA) blood test. These tests prove that the person’s immune system has been exposed to TB bacteria.^[3]

Next, it is essential to confirm that the person does not have active TB disease. This usually involves a chest X-ray to ensure the lungs appear normal, as well as a review of symptoms. If the person has a cough, fever, night sweats, unexplained weight loss, or other signs of active disease, they would not qualify for a latent TB trial and would instead need treatment for active disease.^[9]

Clinical trials may also require additional tests to assess a person’s overall health and determine whether they are suitable for the study medication. For example, blood tests might be performed to check liver and kidney function, as some TB medications can affect these organs. Depending on the trial, other tests such as HIV screening might be required, especially since people with HIV are at higher risk of TB progression and are often included in specialized trials.^[10]

Some trials focus on specific populations, such as children, pregnant women, or people with certain medical conditions like diabetes or kidney disease. In these cases, additional diagnostic tests might be needed to confirm that the person meets the study’s inclusion criteria. For instance, a trial for pregnant women might require an ultrasound to confirm pregnancy, while a trial for people with diabetes might require blood sugar tests.^[10]

Participation in a clinical trial is voluntary, and all tests are performed to ensure the safety and well-being of participants. Researchers use these diagnostic tests not only to select appropriate participants but also to monitor their health throughout the study and measure how well the treatment is working.