What is the recommended treatment for individuals with high-risk exposure to tuberculosis (TB)?

Treatment for High-Risk TB Exposure

Individuals with high-risk exposure to tuberculosis should receive preventive treatment regardless of age, tuberculin skin test results, or history of previous TB preventive treatment, with the preferred regimen being 9 months of daily isoniazid or 3-4 months of rifampin-based therapy. 1, 2

Immediate Evaluation After Exposure

• All exposed individuals should be evaluated for active TB disease as soon as possible (ideally within 7 days) after learning of exposure to an infectious TB patient. 1
• Active TB disease must be ruled out before initiating preventive therapy through clinical evaluation, chest radiography, and symptom assessment. 1, 2
• HIV-infected persons should receive a tuberculin skin test (TST) regardless of any previous TST results. 1

Priority Groups for Preventive Treatment

The following groups warrant immediate preventive treatment after excluding active TB disease:

• HIV-infected contacts should receive TB preventive treatment regardless of TST results, age, or history of previous treatment. 1, 2
• Children under 5 years of age who are close contacts of infectious TB cases. 1, 2
• Persons with TST reaction ≥5 mm who have not previously received treatment for M. tuberculosis infection. 1
• Contacts with documented TST conversion from negative to positive. 1

Recommended Preventive Therapy Regimens

For Drug-Susceptible TB Exposure

Standard regimens for contacts of drug-susceptible TB:

• 9 months of daily isoniazid (10 mg/kg, maximum 300 mg daily) is the preferred regimen for HIV-infected adults. 1, 2
• 12 months of daily isoniazid is recommended for HIV-infected children. 1, 2
• 4 months of daily rifampin is an acceptable alternative for contacts who cannot tolerate isoniazid. 1, 2
• 3 months of weekly isoniazid plus rifapentine (3HP) is emerging as an option for persons >2 years, though not yet widely available. 3

For Drug-Resistant TB Exposure

Preventive therapy must be tailored based on the resistance pattern of the index case:

• For isoniazid-resistant, rifampin-susceptible TB: 4 months of daily rifampin is recommended. 1, 2
• For multidrug-resistant TB (MDR-TB): Consultation with a TB expert is mandatory, as no regimen has been fully validated. 1, 2
• Contacts diagnosed with MDR-TB infection should be monitored for 2 years after exposure. 1

Window-Period Prophylaxis

For highly vulnerable contacts with negative initial TST, window-period prophylaxis should be initiated while awaiting repeat testing:

• HIV-infected persons, organ transplant recipients, and those on TNF-α antagonists should receive prophylactic treatment even with negative TST results if exposure was significant. 1
• Consider frequency, duration, and intensity of exposure (brief exposure to highly contagious TB in confined space warrants same concern as extended exposure to less contagious patients). 1
• Corroborative evidence of transmission from the index patient (substantial fraction of contacts with positive TST results) supports treatment decision. 1

Special Population Considerations

HIV-Infected Individuals

• 9-month daily isoniazid regimen is the standard for HIV-infected adults. 1, 2
• For HIV-infected adults on protease inhibitors or NNRTIs, rifampin-containing regimens are contraindicated; rifabutin may be substituted. 1
• Rifabutin is contraindicated with ritonavir, hard-gel saquinavir, and delavirdine. 1
• Primary prophylaxis for TST-negative, HIV-infected persons with ongoing unavoidable high-risk exposure (prisons, jails, homeless shelters with high TB prevalence) should be considered. 1

Pregnant Women

• Isoniazid is the prophylactic agent of choice for pregnant women after excluding active TB. 2
• Providers may choose to initiate prophylaxis after the first trimester due to theoretical teratogenicity concerns, though treatment should not be delayed if risk is high. 1, 2

Implementation and Monitoring

Directly Observed Preventive Therapy (DOPT)

DOPT should be prioritized for the following high-risk groups:

• Contacts aged <5 years. 1
• HIV-infected or otherwise substantially immunocompromised contacts. 1
• Contacts with TST conversion from negative to positive. 1
• Contacts with social or behavioral impediments to adherence (alcohol addiction, chronic mental illness, injection drug use, unstable housing, unemployment). 1
• All patients on twice-weekly dosing regimens should receive DOPT. 1

Monthly Monitoring Requirements

• All persons undergoing preventive treatment should receive monthly clinical evaluation for adherence and medication side effects. 1
• Check for signs or symptoms of active TB disease (cough, fever, night sweats, weight loss) at each visit. 1
• Baseline hepatic function tests (AST, ALT, bilirubin) should be obtained for patients with risk factors for hepatotoxicity (hepatitis B or C, alcohol abuse, HIV infection). 1
• Routine hepatic function monitoring during treatment is not necessary unless baseline abnormalities exist or symptoms develop. 1

Common Pitfalls and How to Avoid Them

Critical errors to prevent:

• Failing to rule out active TB before starting preventive therapy can lead to inadequate treatment and development of drug resistance. Obtain chest radiography and assess for symptoms in all contacts before initiating prophylaxis. 1, 2
• Using rifampin-containing regimens in patients on protease inhibitors or NNRTIs causes dangerous drug interactions. Verify all medications before prescribing; substitute rifabutin when necessary. 1
• Discontinuing preventive therapy prematurely after interruptions >2 months without medical re-evaluation for active TB disease. Always perform clinical examination and consider chest radiography before restarting therapy. 1
• Failing to provide DOT for high-risk contacts leads to poor completion rates. The national objective is 85% treatment completion, but operational studies show this is not being achieved without DOT. 1
• Not consulting TB experts for MDR-TB contacts results in inappropriate regimen selection. These regimens are poorly tolerated and lack full efficacy data; expert guidance is essential. 1

Treatment Completion Goals

• The national health objective is to achieve 85% treatment completion rate for infected contacts who start treatment. 1
• Incentives (food coupons, toys for children) and enablers (transportation vouchers) should be provided to improve adherence. 1
• Education regarding TB, its treatment, and signs of adverse drug effects should be part of each patient encounter. 1