Tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis, which most commonly affects the lungs but can occur elsewhere in the body. A positive result on an initial screening test, such as a Tuberculin Skin Test (TST) or an Interferon-Gamma Release Assay (IGRA), is not a final diagnosis. Instead, it confirms that the bacteria have entered the body and triggered an immune response, initiating a medical evaluation.
What a Positive Result Indicates
A positive TB screening test confirms the presence of M. tuberculosis bacteria but does not specify the stage of infection. Healthcare providers must distinguish between Latent TB Infection (LTBI) and Active TB Disease. In LTBI, the immune system has successfully walled off the bacteria, keeping them inactive and preventing rapid multiplication.
Individuals with LTBI are asymptomatic, meaning they do not feel sick or experience symptoms like a persistent cough, fever, or night sweats. People with latent infection are not contagious and cannot spread the bacteria to others. However, without treatment, there is a risk that the latent infection could progress to active disease, with about 5% to 10% of infected persons developing active TB.
Active TB Disease occurs when the bacteria overcome immune defenses and begin to multiply, causing tissue damage, usually in the lungs. This leads to symptoms like a prolonged cough lasting three weeks or more, chest pain, or coughing up blood or sputum. A person with active pulmonary TB is contagious and can transmit the bacteria through the air. Screening tests confirm exposure and infection, requiring further investigation to determine the current state.
Confirmatory Testing and Diagnosis
Following a positive screening test, a definitive diagnosis requires follow-up procedures to determine if the infection is latent or active. The process begins with a comprehensive medical history and a physical examination to check for symptoms. The provider will ask about risk factors, such as contact with an active TB patient or travel to high-prevalence areas.
The next step is obtaining a Chest X-ray to look for characteristic changes in the lungs, such as infiltrates or cavities, that suggest active disease. If the Chest X-ray is normal and the patient has no symptoms, the diagnosis is typically Latent TB Infection, and preventative treatment is offered. An abnormal Chest X-ray or the presence of symptoms necessitates immediate testing for active disease.
If active TB is suspected, a sputum test is collected for laboratory analysis. The sputum, which is thick mucus coughed up from the lungs, is tested using an acid-fast bacilli (AFB) smear and culture to confirm the presence of M. tuberculosis. A positive culture definitively diagnoses active TB and is used for drug susceptibility testing, which helps select the most effective antibiotic regimen. A positive screening test alone is never sufficient to diagnose active TB disease.
Treatment Approaches for TB
The treatment pathway is determined by whether the patient has Latent TB Infection or Active TB Disease. For LTBI, the primary goal is to prevent progression to the active, contagious form. Current guidelines favor shorter regimens, such as a three-month course of weekly isoniazid and rifapentine (3HP) or a four-month course of daily rifampin.
These rifamycin-based regimens are often preferred over the traditional six-to-nine month daily course of isoniazid alone due to higher completion rates and similar efficacy. Treating LTBI is a preventative measure, significantly lowering the lifetime risk of developing active disease by killing the dormant bacteria. Treatment is especially important for individuals with weakened immune systems.
Active TB Disease requires a more intensive, multi-drug approach to rapidly eliminate multiplying bacteria and prevent drug resistance. The initial phase typically involves a combination of four drugs—isoniazid, rifampin, pyrazinamide, and ethambutol (RIPE)—taken daily for two months. This is followed by a continuation phase, usually consisting of isoniazid and rifampin for an additional four to seven months.
The total duration of active TB treatment is typically six to nine months. Adherence is monitored through Directly Observed Therapy (DOT), where a healthcare worker watches the patient take their medication. Completing the full course of antibiotics is necessary to ensure all bacteria are eradicated and to prevent the development of drug-resistant strains of TB.
Contextual Factors Affecting Test Results
While TB screening tests are generally reliable, certain factors can influence the results. One common cause of a false-positive result on the Tuberculin Skin Test (TST) is prior vaccination with the Bacillus Calmette-Guérin (BCG) vaccine. This vaccine, widely used in high-prevalence countries, can sensitize the immune system, leading to a positive TST reaction without true M. tuberculosis infection.
The Interferon-Gamma Release Assay (IGRA) blood test measures the immune response to specific TB antigens not found in the BCG vaccine. IGRA is significantly less affected by vaccination history and is often preferred for individuals who have received the BCG vaccine. Healthcare providers consider this history when interpreting a TST result.
A false-negative result can occur in individuals with a severely compromised immune system, a phenomenon known as anergy. People with advanced HIV infection or those on high-dose immunosuppressive medications may not mount a strong enough immune reaction to the test antigens. In such cases, a full clinical evaluation and Chest X-ray are required regardless of a negative screening result if symptoms are present.