LTBI – The Importance of Tackling Latent TB Infection
Latent tuberculosis infection (LTBI) is the presence of Mycobacterium tuberculosis in the body without signs and symptoms, or radiographic or bacteriologic evidence of TB disease.1 People with LTBI cannot spread the TB bacteria to others. However, if the TB bacteria become active and multiply, latent infection can turn into TB disease.
The Challenge Posed by Untreated LTBI
In the US, up to 13 million people have latent TB infection, according to CDC estimates.2 Even more concerning is the fact that 80 percent of TB diagnoses in the US are linked to individuals who lived for years with untreated latent TB infection.2 Thus, health authorities recommend treating LTBI in high risk populations.
Testing Those at High Risk for LTBI
Since LTBI has no symptoms, a diagnosis begins with testing to detect TB bacteria in the body using one of two types of diagnostic tests – the tuberculin skin test (TST) and an FDA-approved Interferon–Gamma Release Assay (IGRA) blood test.3
Tuberculin skin test (TST)
The TB skin test, also called the Mantoux tuberculin skin test,4 is the preferred diagnostic method for children under age 5. Requiring 2 visits to a health provider, the TST entails injecting a small amount of a tuberculin purified protein derivative (PPD) into the skin of the lower part of the arm. After 2 to 3 days, a trained health care worker measures the size of the raised hard area or swelling, if any, to determine if the reaction is positive or negative. However, a negative test does not always mean the person is free of TB bacteria.5
IGRA Blood Tests
The FDA has approved 2 ICRA blood tests to detect LTBI — QuantiFERON®-TB Gold-in-Tube test (QFT-GIT) and the T-SPOT® TB test. Both tests assess immune reactivity to the M. tuberculosis bacteria by measuring the response of TB proteins when mixed with a small amount of blood. One visit is required to draw blood for the test and results are available in 24 hours.5
Because a positive TB skin test or TB blood test determines infection with TB bacteria but not whether the person has latent TB or active disease, a final diagnosis requires additional tests, such as a chest x-ray and a sample of sputum.3
Who Are Priorities for Screening
The CDC recommends screening individuals at high risk for TB disease to diagnose and treat LTBI. Populations considered top priorities are:2
- Persons who were born in, or are former residents of, countries with increased exposure to tuberculosis and person who live in, or have lived in, high-risk congregate settings
- Persons who are contacts of individuals with active tuberculosis, including health care workers
- Populations at increased risk for LTBI include persons who are Immunosuppressed such as those with HIV and diabetes with latent TB infection but at increase risk of progressing to TB disease such as those with HIV, diabetes, recently infected with TB bacteria (in the last 2 years) and those who use of illegal drugs or abuse of alcohol.
Why Treating LTBI is a National Priority
National TB surveillance data, combined with information from recent outbreak investigations, confirm that preventing the transmission of infectious TB disease remains a challenge.
After years of progress, TB rates have stopped declining among people born in the US.2 Moreover, there has been no significant change in the rate of latent TB infection over the last decade6 at a time when more than 80 percent of active TB cases are associated with undiagnosed and untreated LTBI.2 Progress toward reducing the incidence of TB disease requires increased efforts to detect and treat latent TB infection in high-risk populations.
Important Safety Information for PRIFTIN® (rifapentine)
Priftin is contraindicated in patients with a history of hypersensitivity to rifamycins.
Elevations of liver transaminases may occur in patients receiving Priftin. Patients should be monitored for symptoms of liver injury. Patients with abnormal liver function tests and/or liver disease or patients initiating treatment for active pulmonary tuberculosis should only be given Priftin in cases of necessity and under strict medical supervision. Discontinue Priftin if evidence of liver injury occurs.
Hypersensitivity reactions may occur in patients receiving Priftin. Signs and symptoms of these reactions may include hypotension, urticaria, angioedema, acute bronchospasm, conjunctivitis, thrombocytopenia, neutropenia or flu-like syndrome. There have been reports of anaphylaxis. Monitor patients for signs and/or symptoms of hypersensitivity reactions. If these symptoms occur, administer supportive measures and discontinue Priftin.
Severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome have been reported in association with the use of rifapentine (Priftin) treatment regimens in patients with active and latent tuberculosis. Discontinue Priftin at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Higher relapse rates may occur in patients with cavitary pulmonary lesions and/or positive sputum cultures after the initial phase of active tuberculosis treatment and in patients with evidence of bilateral pulmonary disease. Monitor for signs and symptoms of relapse in these patients.
Rifapentine is an inducer of Cytochrome P450 enzymes. Concomitant use of rifapentine with other drugs metabolized by these enzymes, such as protease inhibitors, certain reverse transcriptase inhibitors, and hormonal contraception may cause a significant decrease in plasma concentrations and loss of therapeutic effect of these drugs. Dosage adjustment of the drugs may be necessary.
Priftin may produce a red-orange discoloration of body tissues and/or fluids and may permanently stain contact lenses or dentures red-orange.
Clostridioides difficile-associated diarrhea (CDAD) has been reported with the use of nearly all systemic antibacterial agents, including Priftin, with severity ranging from mild diarrhea to fatal colitis. CDAD must be considered in all patients who present with diarrhea following antibacterial use. If CDAD is suspected or confirmed, discontinue antibacterial use not directed against C. difficile if possible and institute appropriate treatment measures.
Avoid the use of Priftin in patients with porphyria.
In Priftin studies, the most common adverse reactions with the regimen for active pulmonary tuberculosis (≥3%) are anemia, lymphopenia, hemoptyis, neutropenia, cough, thrombocytosis, increased sweating, increased ALT, increased AST, back pain, rash, anorexia, arthralgia, increased blood urea, and headache. The most common adverse reaction (≥3%) with the regimen for latent tuberculosis infection is hypersensitivity reaction.
Active Pulmonary Tuberculosis
Priftin® (rifapentine) is indicated in adults and children 12 years and older for the treatment of active pulmonary tuberculosis caused by Mycobacterium tuberculosis. Priftin must always be used in combination with one or more antituberculosis drugs to which the isolate is susceptible.
Limitations of Use:
- Do not use Priftin monotherapy in either the initial or the continuation phases of active antituberculous treatment.
- Priftin should not be used once-weekly in the continuation phase regimen in combination with isoniazid (INH) in HIV-infected patients with active pulmonary tuberculosis because of a higher rate of failure and/or relapse with rifampin-resistant organisms.
- Priftin has not been studied as part of the initial phase treatment regimen in HIV-infected patients with active pulmonary tuberculosis.
Latent Tuberculosis Infection
Priftin is indicated in adults and children 2 years and older for the treatment of latent tuberculosis infection caused by Mycobacterium tuberculosis in patients at high risk of progression to tuberculosis disease (including those in close contact with active tuberculosis patients, recent conversion to a positive tuberculin skin test, HIV-infected patients, or those with pulmonary fibrosis on radiograph).
Limitations of Use:
- Active tuberculosis disease should be ruled out before initiating treatment for latent tuberculosis infection.
- Priftin must always be used in combination with INH as a 12-week once-weekly regimen for the treatment of latent tuberculosis infection. Priftin in combination with INH is not recommended for Individuals presumed to be exposed to rifamycin- or - INH resistant M. tuberculosis.