TB Infection Transmission Timeline and Treatment
When TB Infection Can Spread After Exposure
TB infection becomes detectable 8-10 weeks after exposure, which represents the critical "window period" for developing a measurable immune response on tuberculin skin testing or interferon-gamma release assays. 1
The Window Period Explained
- The immune system requires 8-10 weeks after Mycobacterium tuberculosis exposure to mount a detectable response that can be identified through testing. 1
- During this 8-10 week window, an exposed person may be infected but test negative because the immune response has not yet developed sufficiently for detection. 1
- Two-step testing is mandatory: an immediate test when exposure is identified, followed by repeat testing 8-10 weeks post-exposure if the initial test is negative. 1
Critical Clinical Pitfall to Avoid
Never assume a negative test during the first 8 weeks post-exposure rules out infection—this is the most critical error in TB contact management. 1 The person may be infected but simply hasn't developed a detectable immune response yet.
Immediate Management of High-Risk Contacts
Who Needs Window-Period Prophylaxis
Children under 5 years must begin treatment for presumptive infection (window prophylaxis) immediately after excluding active disease, even with negative initial testing. 1 This is because young children are highly vulnerable to severe disseminated TB and TB meningitis. 1
Additional high-risk groups requiring immediate prophylactic treatment after active disease is excluded include:
- HIV-infected contacts 1
- Immunocompromised contacts (organ transplant recipients, those on TNF-α antagonists) 1
- Infants and toddlers aged <3 years (especially critical) 2
The Two-Test Protocol
- First test: Perform immediately when exposure is identified to establish baseline status. 1
- Second test: Repeat 8-10 weeks after the last exposure for all contacts with initial negative results. 1
- If the second test is positive, this indicates infection occurred during the exposure period and warrants full treatment for latent TB infection. 1, 3
- If the second test remains negative in children <5 years who received window prophylaxis, treatment may be stopped. 2
Treatment of Latent TB Infection (LTBI)
Preferred First-Line Regimens
The CDC strongly recommends a 4-month daily regimen of rifampin as the preferred treatment for latent TB infection, with moderate quality evidence. 3 This regimen offers:
- Shorter duration than isoniazid-based regimens
- Better completion rates 3
- Fewer drug interactions than combination regimens 3
Alternative preferred option: 3-month once-weekly isoniazid plus rifapentine (strongly recommended with moderate quality evidence), which may be considered if daily medication is challenging. 3 This regimen should be given as directly observed therapy. 3
Additional Treatment Options
- 9 months of daily isoniazid: Provides better efficacy than 6-month regimens but has lower completion rates. 3 This is the traditional standard. 2
- 6 months of daily isoniazid: Strongly recommended with moderate quality evidence in HIV-negative patients, less effective than longer courses but may be better tolerated. 3
- 3 months of daily isoniazid plus rifampin: Conditionally recommended with very low quality evidence in HIV-negative patients. 3
Special Population Considerations
For HIV-infected persons or those with radiographic evidence of prior TB, 9 months rather than 6 months of isoniazid is recommended. 2
For pregnant, HIV-negative women: Isoniazid given daily or twice weekly for 9 or 6 months is recommended. 2 For women at risk for progression (especially HIV-infected or recently infected), initiation should not be delayed based on pregnancy alone, even during the first trimester. 2
For children and adolescents: Isoniazid given either daily or twice weekly for 9 months is the recommended regimen. 2
For contacts of isoniazid-resistant, rifampin-susceptible TB: Rifampin and pyrazinamide given daily for 2 months is recommended; for those with pyrazinamide intolerance, rifampin given daily for 4 months is recommended. 2
For contacts of multidrug-resistant TB: Pyrazinamide and ethambutol or pyrazinamide and a quinolone (levofloxacin or ofloxacin) for 6-12 months are recommended. 2 Immunocompetent contacts may be observed or treated for at least 6 months; immunocompromised contacts should be treated for 12 months. 2
Pre-Treatment Evaluation
Before starting treatment, active TB must be ruled out through:
- History and physical examination focusing on TB symptoms (productive cough, fever, night sweats, weight loss, hemoptysis) 4
- Chest radiography to identify cavitary lesions, infiltrates, or other abnormalities 4
- When indicated, bacteriologic studies including sputum for acid-fast bacilli smear and culture 4
- Baseline liver function tests for high-risk patients 2, 4
Who Needs Baseline Laboratory Testing
Baseline hepatic measurements (AST/ALT and bilirubin) are indicated for: 2
- Patients with HIV infection
- Pregnant women
- Women in the immediate postpartum period (within 3 months of delivery)
- Patients whose initial evaluation suggests a liver disorder
- History of liver disease or regular alcohol use 4
Monitoring During Treatment
Clinical Monitoring Schedule
For patients receiving isoniazid alone or rifampin alone: At least monthly evaluations. 2
For patients receiving rifampin and pyrazinamide: Evaluations at 2,4, and 8 weeks. 2
Each evaluation should include:
- Questioning about side effects 2
- Brief physical assessment checking for signs of hepatitis 2
- Patient education about side effects with instructions to stop treatment and promptly seek medical evaluation when they occur 2
When to Stop Treatment
Discontinue isoniazid immediately if:
- Aminotransferases exceed 5 times the upper limit of normal in asymptomatic patients 4
- Aminotransferases exceed 3 times the upper limit of normal with symptoms 4
Critical Caveats
Do not delay prophylactic treatment in high-risk contacts (especially young children) while waiting for the 8-10 week repeat test. 1 The risk of progression to severe disease outweighs the inconvenience of potentially unnecessary treatment.
Never confuse treatment regimens for latent TB infection with those for active TB disease. 3 Active TB requires multi-drug therapy to prevent resistance; LTBI can be treated with single or dual-drug regimens.
Ensure that active TB has been ruled out before starting treatment for latent TB infection. 3 Adding a single drug to unrecognized active disease may lead to drug resistance. 3
Directly observed therapy should be considered for all LTBI patients to ensure completion, particularly with the once-weekly rifapentine/isoniazid regimen. 3