What is the recommended treatment for latent tuberculosis (TB) infection after exposure to TB?

Treatment for Latent Tuberculosis Infection After TB Exposure

All contacts of persons with active TB should be treated for latent tuberculosis infection (LTBI) after excluding active disease, regardless of tuberculin skin test (TST) or interferon-gamma release assay (IGRA) results, particularly for high-risk individuals including children under 5 years and immunocompromised persons. 1, 2

Immediate Assessment Required

Before initiating LTBI treatment, the following steps are mandatory:

• Obtain a chest radiograph (posterior-anterior view) to exclude active pulmonary TB disease 1, 2
• Assess for TB symptoms including persistent cough, weight loss, night sweats, hemoptysis, fever, or anorexia 1, 2
• Report the exposure to local public health authorities immediately for contact investigation 2

Recommended Treatment Regimens for Drug-Susceptible TB Exposure

The following regimens are recommended based on current guidelines:

First-Line Options:

• 9 months of daily isoniazid (5 mg/kg, maximum 300 mg daily) - the most extensively studied regimen 3, 1, 4
• 3-4 months of daily isoniazid plus rifampin (isoniazid 5 mg/kg max 300 mg + rifampin 10 mg/kg max 600 mg) - shorter duration with similar efficacy 3, 1, 4
• 12 weeks of once-weekly rifapentine plus isoniazid (rifapentine dose based on weight, isoniazid 15 mg/kg max 900 mg for adults ≥12 years; isoniazid 25 mg/kg max 900 mg for children 2-11 years) as directly observed therapy 4, 5
• 4 months of rifampin alone for patients with pyrazinamide intolerance 3, 4

Alternative Regimen:

• 6 months of daily isoniazid as an alternative to the 9-month regimen 2, 4

Special Populations Requiring Immediate Treatment

Children Under 5 Years:

• Treat immediately after excluding active TB, even if initial TST/IGRA is negative (window prophylaxis) 3
• Repeat TST/IGRA 8-12 weeks after last exposure 3
• If repeat test is positive, complete full LTBI treatment course 3
• If repeat test remains negative, discontinue treatment 3

Immunocompromised Persons (Including HIV-Infected):

• Treat for full LTBI course even if repeat testing remains negative after excluding active disease 3
• HIV infection increases TB reactivation risk substantially; TST reaction ≥5 mm is considered positive 1
• Extend treatment to at least 9 months for HIV co-infected patients 4
• Baseline and ongoing laboratory monitoring is mandatory 1
• Consider drug interactions with antiretroviral therapy, particularly with rifampin-containing regimens 1

Baseline Laboratory Testing

Testing requirements vary by risk factors:

• Obtain baseline AST/ALT and bilirubin for patients with: 3, 1

  • HIV infection
  • History of chronic liver disease (hepatitis B/C, alcoholic hepatitis, cirrhosis)
  • Regular alcohol use
  • Pregnancy or within 3 months postpartum
  • Concurrent use of other hepatotoxic medications

• Baseline testing not routinely required for otherwise healthy adults without risk factors 3, 1

Monitoring During Treatment

Clinical Monitoring:

• Schedule monthly visits to assess adherence and monitor for adverse effects 1, 2
• Educate patients about hepatotoxicity symptoms: nausea, vomiting, abdominal pain, dark urine, jaundice 2
• Add pyridoxine (vitamin B6, 25-50 mg daily) to prevent peripheral neuropathy when using isoniazid 2

Laboratory Monitoring:

• Routine monthly laboratory monitoring not required for patients with normal baseline tests and no risk factors 1
• Perform liver function tests if symptoms of hepatotoxicity develop 3, 1
• Withhold isoniazid if transaminase levels exceed 3 times upper limit of normal with symptoms, or 5 times upper limit without symptoms 3

Treatment for Isoniazid-Resistant TB Exposure

When the source case has confirmed or probable isoniazid-resistant, rifampin-susceptible TB:

• 2 months of rifampin plus pyrazinamide is recommended 3
• 4 months of rifampin alone for patients with pyrazinamide intolerance 3
• Rifabutin can substitute for rifampin when rifampin cannot be used 3
• This is particularly important for vulnerable contacts (e.g., HIV-infected persons) 3

Treatment for Multidrug-Resistant TB (MDR-TB) Exposure

For exposure to TB resistant to both isoniazid and rifampin:

• Pyrazinamide plus ethambutol OR pyrazinamide plus fluoroquinolone (levofloxacin or ofloxacin) for 6-12 months, if organisms are susceptible to these agents 3
• Immunocompetent contacts: may be observed without treatment or treated for at least 6 months 3
• Immunocompromised contacts: should be treated for 12 months 3
• All persons with suspected MDR-TB infection should be followed for at least 2 years, regardless of treatment 3
• Expert consultation should be sought for all MDR-TB exposures 3

Critical Timing Considerations

When Source Case Has Active TB Not Yet on Treatment:

• Anti-TNF therapy should be delayed for at least 3 weeks after starting LTBI chemotherapy in patients with latent TB and active IBD, except in cases of greater clinical urgency with specialist advice 3
• The spouse with active TB should be started on appropriate multidrug treatment as soon as possible to reduce ongoing transmission risk 2

Common Pitfalls to Avoid

• Do not wait for TST/IGRA results before treating high-risk contacts (children <5 years, immunocompromised) - treat immediately after excluding active disease 3
• TST may be false negative in patients on corticosteroids >1 month or immunomodulators >3 months; cannot be adequately interpreted unless these are discontinued 3
• Consider booster TST 1-2 weeks after initial negative test in patients on immunomodulators, as this diagnoses 8-14% additional cases 3
• Any TST ≥5 mm should be considered positive for latent TB in contact investigations 3
• IGRAs are preferred in BCG-vaccinated individuals as they have better specificity 3, 6, 7
• Active hepatitis and end-stage liver disease are relative contraindications to isoniazid or pyrazinamide 3