Does a patient with no symptoms and a negative Quantiferon (Interferon-Gamma Release Assay) test require treatment for latent tuberculosis (TB) infection after recent close contact with active pulmonary tuberculosis?

From the Guidelines

No, a patient with no symptoms and a negative Quantiferon test generally does not require treatment for latent tuberculosis infection after recent close contact with active pulmonary TB. This recommendation is based on the guidelines provided by the World Health Organization, as stated in the European Respiratory Journal study 1, which suggests that either interferon-gamma release assays (IGRA) or Mantoux tuberculin skin test (TST) should be used to test for latent tuberculosis infection (LTBI) in individuals who have been in close contact with pulmonary TB cases. However, some key considerations must be taken into account:

• The timing of the exposure: If the exposure was very recent (within 8-10 weeks), the test may need to be repeated after the "window period" because the immune response may not have developed sufficiently for detection 1.
• Patient risk factors: For immunocompromised individuals or children under 5, prophylactic treatment might still be considered despite negative results due to their higher risk of progression to active disease.
• The infectiousness of the index case: This can influence the decision to treat or monitor closely. If treatment were indicated, options would include:
• Isoniazid (INH) 300mg daily for 6-9 months
• Rifampin 600mg daily for 4 months
• The combination of INH 900mg plus rifapentine 900mg weekly for 12 weeks, as recommended by the guidelines 1. Close clinical monitoring for TB symptoms remains important regardless of the initial test result, and individuals should be asked about symptoms of TB before being tested for LTBI, with chest radiography considered if efforts are intended for active TB case finding 1.

From the FDA Drug Label

1.2 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) Active tuberculosis disease should be ruled out before initiating treatment for latent tuberculosis infection.

The patient had a recent close contact with active pulmonary tuberculosis and has no symptoms, but the Quantiferon test came back negative.

• The FDA drug label does not explicitly state what to do in the case of a negative Quantiferon test after close contact with active pulmonary tuberculosis.
• However, it does indicate that PRIFTIN is used for the treatment of latent tuberculosis infection in patients at high risk of progression to tuberculosis disease, including those in close contact with active tuberculosis patients.
• Since the patient has no symptoms and the Quantiferon test is negative, treatment for latent tuberculosis infection may not be necessary.
• But, according to the label, active tuberculosis disease should be ruled out before initiating treatment for latent tuberculosis infection.
• Therefore, further evaluation is needed to determine if the patient requires treatment for latent tuberculosis infection 2.

From the Research

Latent Tuberculosis Infection Treatment

• A patient with no symptoms and a negative Quantiferon test result after recent close contact with active pulmonary tuberculosis may not require treatment for latent tuberculosis (TB) infection, as the Quantiferon test is used to diagnose latent TB infection 3.
• However, it is essential to consider the context of the exposure and the individual's risk factors, as the Quantiferon test may not always be accurate in detecting latent TB infection, especially in certain populations or after recent exposure 4.
• The Centers for Disease Control and Prevention (CDC) recommend treating individuals with latent TB infection to prevent the development of active TB disease, especially if they have been in close contact with someone with active TB 5, 6, 7.

Quantiferon Test Results

• A negative Quantiferon test result does not necessarily rule out the possibility of latent TB infection, as the test may have false-negative results, especially in individuals with weakened immune systems or recent exposure to TB 3, 4.
• The Quantiferon test measures the immune response to TB antigens, and a negative result may indicate that the individual has not been infected with TB or that their immune system is not responding to the antigens 3.

Treatment Options

• The treatment of latent TB infection typically involves a course of antibiotics, such as isoniazid, to kill the dormant TB bacteria in the body 5, 6, 7.
• The duration and type of treatment depend on the individual's risk factors, medical history, and the results of their diagnostic tests 5, 6, 7.
• In some cases, a shorter course of treatment, such as a 3-month regimen of weekly rifapentine plus isoniazid, may be recommended for individuals with latent TB infection 6, 7.