Clinical Overview of Tuberculosis Disease

Pulmonary TB disease affects the lungs. People with pulmonary TB disease usually have a cough and an abnormal chest radiograph. They may be infectious. Most TB cases are pulmonary.

Extrapulmonary TB disease occurs in places other than the lungs, including the larynx, the lymph nodes, the pleura, the brain, the kidneys, or the bones and joints. TB disease can occur anywhere in the body. People with extrapulmonary TB disease are usually not infectious unless they have:

• Pulmonary disease in addition to extrapulmonary disease;
• Extrapulmonary disease located in the oral cavity or the larynx; or
• Extrapulmonary disease that includes an open abscess or lesion in which the concentration of organisms is high, especially if drainage from the abscess or lesion is extensive or drainage fluid is aerosolized.

People with HIV often have extrapulmonary TB disease and pulmonary TB disease.

Miliary TB disease is a rare but serious condition that occurs when tubercle bacilli enter the bloodstream and disseminate to all parts of the body, where they grow and cause disease in multiple sites. "Miliary" refers to the radiograph appearance of millet seeds scattered through the lung. It is more common in infants and children younger than 5 years of age and in severely immunocompromised people, but anyone could be affected.

Miliary TB disease may be detected in an individual organ (including the brain), in several organs, or throughout the whole body. It is fatal if untreated. Up to 25% of patients with miliary TB disease may have meningeal involvement.

TB meningitis occurs in the tissue surrounding the brain or spinal cord. It is often seen at the base of the brain on imaging studies. In many cases, patients with meningitis have abnormalities on a chest radiograph consistent with old or current TB disease, and they often have miliary TB disease.

Drug-resistant TB disease is caused by M. tuberculosis organisms that are resistant to the drugs normally used to treat the disease. Drug-resistant TB disease is transmitted in the same way as drug-susceptible TB disease, and it is as infectious as drug-susceptible TB disease.

However, delay in the recognition of drug resistance or prolonged periods of infectiousness may facilitate increased transmission and further development of drug resistance.

• 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

A review of systems (medical history) to determine whether the patient:

• Has been exposed to TB bacteria,
• Has been treated for latent TB infection or TB disease in the past, or
• Has medical conditions that should be considered during the evaluation and subsequent treatment.

A physical examination cannot be used to confirm or rule out TB disease. However, it is an essential part of any evaluation and can:

• Provide valuable information about the patient's overall condition
• Inform the method of diagnosis
• Reveal factors that may affect treatment if the patient is diagnosed with TB disease

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

• TB blood tests (Interferon Gamma Release Assay [IGRA])
• TB skin test (Mantoux tuberculin skin test [TST])

Selecting a test

Health care providers should use newer TB blood tests to detect latent TB infection. TB blood tests are preferred for people who have received the BCG vaccine and people who might be less likely to return for TB skin test reading and interpretation. TB skin tests are an acceptable alternative in situations where a TB blood test is not available, is too costly, or is too burdensome.

A negative test result does not rule out TB disease or latent TB infection

Some patients with TB disease may have a negative result from a TB blood test or TB skin test. If a patient has symptoms of TB disease, health care providers should not wait for TB blood test or TB skin test results before starting other diagnostic tests.

The chest radiograph (x-ray) is useful for diagnosis because pulmonary TB is the most common form of TB disease. A chest radiograph can:

• Rule out the possibility of pulmonary TB disease in a person who has a positive TB blood test or TB skin test result, but no symptoms of TB disease
• Check for lung abnormalities in people who have symptoms of TB disease

Abnormal findings on chest radiograph cannot confirm a person has TB disease, but they support the diagnosis.

Clinical specimens (for example, sputum or urine) are examined and cultured (grown) in the laboratory for the bacteriologic examination. TB bacteriologic examination is done in a laboratory that specifically deals with M. tuberculosis and other mycobacteria (a mycobacteriology laboratory). State TB programs can provide consultation and additional information on bacteriologic testing for TB.

The bacteriologic examination has five parts:

1. Specimen collection
2. Examination of smears for acid-fast bacilli
3. Direct detection of TB bacteria in the specimen using a nucleic acid amplification test
4. Specimen culturing and identification of growth
5. Drug susceptibility testing (including genetic testing for genes or mutations that indicate possible drug resistance)

Treatment regimens for TB disease consist of an intensive treatment phase followed by a continuation phase.

If treatment is not continued for a long enough time, the surviving bacilli may cause TB disease in the patient later. The possibility of drug resistance increases if too many doses are missed during the period of treatment, especially if the patient is taking only some of the medicines instead of all of them.

• The intensive phase is used to kill actively growing TB bacilli. This phase of treatment is crucial for preventing emergence of drug resistance and determining the ultimate regimen outcome. For most patients, it brings relief from the disabling symptoms of TB disease.
• The continuation phase is designed to eliminate remaining TB bacilli and to reduce treatment failure and relapse.

There are several treatment regimens recommended in the United States

Treatment for drug-susceptible TB disease can take 4, 6, or 9 months depending on the regimen. Regimens include:

4-month rifapentine-moxifloxacin regimen

The 4-month rifapentine-moxifloxacin TB treatment regimen consists of:

• Isoniazid (H),
• Rifapentine (P),
• Pyrazinamide (Z), and
• Moxifloxacin (M),

The 4-month rifapentine-moxifloxacin regimen (2HPZM/2HPM) has an intensive phase of 2 months, followed by a continuation phase of 2 months and 1 week (a total of 17 weeks for treatment).

6- or 9-month regimens

The 6- to 9-month TB treatment regimens consist of:

• Isoniazid (H),
• Rifampin (R),
• Pyrazinamide (Z), and
• Ethambutol (E).

These regimens for treating TB disease have an intensive phase of 2 months, followed by a continuation phase of either 4 or 7 months (total of 6 to 9 months for treatment).

The goal of treatment for TB disease should be to provide the safest and most effective therapy for the shortest period. Health care providers should choose the appropriate TB treatment regimen based on:

• Drug-susceptibility results,
• Coexisting medical conditions, and
• Potential for drug-drug interactions.

TB disease treatment regimens for patients with special considerations (including pregnant people, breastfeeding people, infants and children, people with HIV, and drug-resistant TB disease) require special management and should be administered in consultation with a TB expert. In some circumstances, the organ site of TB disease is also a factor in the treatment regimen and duration of treatment.

Baseline monitoring

Before starting treatment, adult patients should have certain baseline blood and vision tests to help detect any underlying problems that can complicate treatment. For pediatric patients, only vision tests are necessary unless other medical conditions exist that might complicate treatment.

Monitoring during treatment

Patients being treated for TB disease should have clinical evaluations at least monthly to assess medication adherence and to identify possible adverse reactions to medications.

Adverse reactions to anti-TB drugs are relatively rare, but for certain patients, they can be severe. Consult a TB medical expert to assist in managing serious adverse reactions Mild adverse effects can usually be managed by adjusting the timing of the medications, by taking the medications with food, or by symptomatic therapy.

Health care providers must ensure patients with TB disease follow the recommended treatment course in order to treat TB disease and prevent the infection from becoming drug resistant. Health care providers should consult their state or local TB program to help identify strategies to help patients complete treatment.

CDC recommends directly observed therapy (DOT) as the standard of care for treating TB disease. During DOT, a health care worker observes (in-person or virtually) patients ingest their medications, monitors them for adverse events, and provides social support.