Pulmonary tuberculosis is an infectious disease caused by Mycobacterium tuberculosis that primarily affects the lungs and spreads through the air. There are two states of this condition: latent TB infection (LTBI) and active pulmonary TB. In LTBI, the bacteria are present but contained by the immune system, causing no symptoms and being non-contagious.
Active TB develops when the immune system can no longer control the bacteria, leading to their multiplication and symptoms like a persistent cough, fever, and weight loss. The transition from a dormant infection to a transmissible disease is triggered by specific circumstances that compromise the body’s defensive capabilities.
Weakened Immune System due to HIV Infection
The primary risk factor for the progression of latent TB to active disease is a co-infection with the human immunodeficiency virus (HIV). HIV targets the immune system, attacking and destroying a type of white blood cell known as the CD4+ T-cell. These cells are instrumental in the body’s defense against the TB bacteria, as the immune response contains M. tuberculosis within cellular structures called granulomas.
The integrity of these granulomas depends on a healthy population of CD4+ T-cells. HIV infection depletes these cells, weakening the structures that keep the TB bacteria dormant. As the CD4+ cell count declines, the body’s containment fails, allowing the bacteria to replicate and cause active pulmonary tuberculosis.
A person living with HIV who also has a latent TB infection is many times more likely to develop active TB disease than someone without HIV. The risk increases as the HIV infection progresses and the immune system becomes more compromised. This association underscores the importance of HIV testing for individuals with TB and TB screening for all people living with HIV.
Other Medical Conditions Weakening Immunity
Beyond HIV, several other chronic medical conditions can impair the immune system and increase the likelihood of latent TB activating. These include:
- Diabetes mellitus. Particularly when poorly controlled, elevated blood sugar levels can hinder the function of immune cells that destroy pathogens like the TB bacteria, making it harder for the body to suppress the infection.
- Chronic kidney disease. The buildup of waste products in the blood (uremia) can weaken the immune response. Patients requiring dialysis are particularly vulnerable because the procedure can affect immune cell function.
- Silicosis. This occupational lung disease results from inhaling silica dust, which scars the lungs and damages alveolar macrophages. This localized damage creates a favorable environment for M. tuberculosis to multiply.
- Cancers. Those affecting the blood and lymphatic system, like leukemia and lymphoma, disrupt the normal function of immune cells, compromising the body’s ability to fight infections.
Medically Induced Immunosuppression
Immune suppression can also be an intended consequence of medical treatment. Certain medications, while necessary for managing health conditions, can leave a patient vulnerable to the activation of latent TB. These treatments work by dampening the immune response, which lowers the body’s guard against dormant pathogens.
A primary category of these drugs is prolonged-use corticosteroids, like prednisone, prescribed for inflammatory conditions. Another group is the TNF-alpha inhibitors, used to treat conditions like rheumatoid arthritis and Crohn’s disease. TNF-alpha is a protein involved in maintaining the granulomas that contain TB bacteria, and blocking it can lead to reactivation.
Individuals who have received organ transplants are also at high risk. They must take anti-rejection medications to prevent their immune systems from attacking the new organ. These drugs suppress the immune system, increasing susceptibility to infections, so it is standard practice for patients to be screened for latent TB before beginning these therapies.
Behavioral and Environmental Determinants
A person’s lifestyle, nutritional status, and living conditions also determine the risk of active TB. Malnutrition is a factor, as a lack of essential nutrients weakens the immune system. This includes deficiencies in calories, vitamins, and minerals that are necessary for proper immune cell function.
Substance use, including alcoholism and smoking, also compromises the body’s defenses. Chronic alcohol consumption impairs the immune response, while tobacco smoke damages the structural and cellular defenses of the lungs. Smoking harms the cilia that clear particles from the airways and affects the function of lung macrophages, making it easier for TB bacteria to establish an active infection.
A person’s environment can also be a determinant. Overcrowded and poorly ventilated settings, such as correctional facilities, homeless shelters, and refugee camps, facilitate the transmission of M. tuberculosis. In these environments, individuals are more likely to be exposed to high bacterial loads, leading to a recent infection, which carries a higher risk of progressing to active disease.