Tuberculosis (TB) is a global bacterial infection caused by Mycobacterium tuberculosis, which typically affects the lungs but can occur anywhere in the body. Most individuals who become infected do not develop active disease. Instead, they enter a state known as Latent Tuberculosis Infection (LTBI), where the bacteria remain alive but inactive within the body. This latent form is a major public health concern because it affects approximately one-quarter of the world’s population, representing a massive reservoir for future active cases.
How Latent TB Differs from Active Disease
In latent infection, the immune system successfully contains the bacteria. This containment means that individuals with LTBI do not feel sick and display no outward signs of illness, such as a cough, fever, or unexplained weight loss.
A person with latent TB is not contagious. The bacteria are not actively multiplying or being expelled into the air through coughing or sneezing. Active TB disease, by contrast, occurs when the immune system fails to control the bacteria, allowing them to multiply and cause tissue damage, most often in the lungs.
Symptoms of active TB include a prolonged cough, chest pain, night sweats, and fatigue, and people with pulmonary active TB can spread the bacteria through the air. While a majority of infected people never progress beyond the latent stage, there is a lifetime risk of about 5–10% that the latent infection will reactivate and become active disease. This progression most often happens when a person’s immune system weakens due to age, certain medical conditions like HIV or diabetes, or immunosuppressive medications.
Methods Used to Identify Latent Infection
Because latent TB is asymptomatic, specialized diagnostic tools are necessary to confirm the presence of the dormant bacteria. The two primary methods are the Tuberculin Skin Test (TST) and the Interferon-Gamma Release Assays (IGRAs). Both tests detect a cellular immune response, which indicates that the body has been exposed to and is currently infected with M. tuberculosis.
The Tuberculin Skin Test involves an intradermal injection of a small amount of purified protein derivative (PPD). The healthcare provider then assesses the injection site 48 to 72 hours later, measuring the diameter of any firm, raised swelling, known as induration, in millimeters. A major limitation of the TST is that a prior vaccination with the Bacille Calmette-Guérin (BCG) vaccine can sometimes cause a false-positive result.
Interferon-Gamma Release Assays (IGRAs) are blood tests that offer an alternative to the TST. These tests measure the release of interferon-gamma after white blood cells are exposed to specific TB-related antigens in a laboratory setting. IGRAs generally require only a single visit for the blood draw and are considered more specific than the TST because their results are not affected by prior BCG vaccination. Testing is typically recommended for individuals at high risk, including close contacts of active TB patients, those born in high-prevalence countries, and people with compromised immune systems.
Treatment and Prevention of Activation
Treatment for latent TB is a form of preventive therapy designed to eliminate the dormant bacteria and prevent the infection from progressing to active TB disease. Successfully treating LTBI can prevent a future illness that would be contagious and more difficult to treat.
Modern treatment guidelines favor shorter, more convenient regimens, which significantly increase the likelihood of patients completing the full course of medication. Preferred options often involve a rifamycin-based regimen, such as three months of once-weekly isoniazid and rifapentine, or four months of daily rifampin. These shorter courses are often preferred over the traditional six-to-nine-month course of isoniazid monotherapy.
The length of treatment must be completed in its entirety to ensure the elimination of the bacteria and to reduce the risk of drug resistance. Due to the potential for liver-related side effects with some medications, regular monitoring and communication with a healthcare provider are important throughout the treatment period.