What are the criteria for tuberculosis (TB) preventive treatment?

Criteria for TB Preventive Treatment

TB preventive treatment should be offered to individuals with documented latent TB infection (positive tuberculin skin test or interferon-gamma release assay) who have specific risk factors for progression to active disease, with the decision based on three key factors: likelihood of true M. tuberculosis infection, risk of progression to active TB, and risk of treatment-related hepatotoxicity. 1

Primary Eligibility Criteria

High-Priority Candidates (Treat Regardless of Age)

Individuals with positive tuberculin skin tests should receive preventive therapy if they have any of the following risk factors 1:

• Recent tuberculin skin test converters (≥10 mm increase within 2 years for those <35 years; ≥15 mm increase for those ≥35 years) 2
• Close contacts of persons with active infectious TB (≥5 mm induration), including tuberculin-negative children/adolescents who should receive therapy until repeat testing 12 weeks after exposure 2
• HIV infection or AIDS (≥5 mm induration) - this is the highest priority group given the substantially elevated risk of progression 1, 2
• Medical conditions increasing TB risk (≥10 mm induration): silicosis, diabetes mellitus, chronic corticosteroid therapy, immunosuppressive therapy, hematologic malignancies (leukemia, Hodgkin's disease), end-stage renal disease, chronic malnutrition, intestinal bypass surgery, gastrectomy, chronic peptic ulcer disease, or oropharyngeal/upper GI carcinomas 2
• Intravenous drug users who are HIV-seronegative (≥10 mm induration) 2
• Abnormal chest radiographs showing fibrotic lesions consistent with old healed TB (≥5 mm induration) 2

Age-Based Criteria for Lower-Risk Individuals

For those under age 35 without the above risk factors, preventive therapy should be considered if they belong to high-incidence groups and have ≥10 mm induration 2:

• Foreign-born persons from high-prevalence countries who never received BCG vaccine 2
• Medically underserved low-income populations, particularly high-risk racial/ethnic minorities (Blacks, Hispanics, Native Americans) 2
• Residents of long-term care facilities (correctional institutions, nursing homes, mental institutions) 2
• Children under 4 years old with ≥10 mm induration 2

For individuals under age 35 with none of the above risk factors but ≥15 mm tuberculin reaction, preventive therapy is appropriate 2.

For individuals over age 35, the risk of isoniazid-associated hepatotoxicity must be carefully weighed against TB risk; treatment is recommended only when additional risk factors (listed above) are present 2.

Special Population Considerations

HIV-Infected Individuals

• Preventive therapy may be considered even for tuberculin-negative HIV-infected persons who belong to groups with high TB prevalence 2
• Treatment duration should be 12 months minimum for HIV-infected patients 2
• For HIV-infected patients on protease inhibitors or NNRTIs, rifampin-containing regimens are contraindicated; rifabutin may be substituted, though rifabutin is contraindicated with ritonavir, hard-gel saquinavir, and delavirdine 1

Pregnant Women

• Preventive therapy can generally be delayed until after delivery due to increased risk of INH-associated hepatitis during the peripartum period 1
• However, for pregnant women with recent infection or high-risk conditions (especially HIV infection), INH preventive therapy should begin immediately when infection is documented 1
• The 9-month isoniazid regimen is the only recommended option for pregnant women 3

Children

• All infants and children younger than 4 years with ≥10 mm skin test are candidates 2
• The American Academy of Pediatrics recommends a 12-month isoniazid regimen for HIV-infected children 3
• Standard duration is 9 months for other children 1

Anergic Patients

Preventive therapy should be considered for anergic persons who are known contacts of infectious TB patients and for those from populations with very high TB prevalence (>10%) 1

Critical Exclusions

Active TB disease must be ruled out before initiating preventive therapy - this is the most critical contraindication 3. Evaluation should include:

• Clinical assessment for TB symptoms 1
• Chest radiography to exclude active disease 2
• Sputum examination if pulmonary TB is suspected 1

Preferred Treatment Regimens (Based on Most Recent Evidence)

The 3-month once-weekly isoniazid plus rifapentine regimen or 4-month daily rifampin are now preferred over traditional 6-9 months of isoniazid monotherapy due to superior completion rates and safety profiles 3:

• 3 months of once-weekly isoniazid plus rifapentine has equivalent effectiveness to 9 months of isoniazid with higher completion rates and less hepatotoxicity in HIV-negative persons 3, 4
• 4 months of daily rifampin is non-inferior to 9 months of isoniazid with significantly better completion (15.1 percentage point difference) and lower rates of grade 3-5 adverse events 5, 3

Alternative Regimens

When shorter regimens cannot be used 3:

• 6 months of daily isoniazid is strongly recommended for HIV-negative adults and children
• 6 months of daily isoniazid is conditionally recommended for HIV-positive adults and children
• For patients intolerant to isoniazid or pyrazinamide, 4 months of daily rifampin is suitable

Special Circumstances

For patients with silicosis or fibrotic pulmonary lesions consistent with healed TB: 12 months of isoniazid OR 4 months of isoniazid plus rifampin 1, 2

For those likely infected with MDR-TB: alternative multidrug preventive therapy regimens should be considered 1

Monitoring Requirements

Baseline Assessment

Baseline laboratory testing is not routinely indicated for all patients but is required for 3:

• Patients with abnormal liver tests or pre-existing liver disease
• HIV-infected individuals
• Pregnant women
• Heavy alcohol users
• History of liver injury

During Treatment

• Monthly clinical evaluation is mandatory for all patients to assess adherence and medication side effects 1, 3
• For persons over age 35, obtain transaminase measurement before initiation and then monthly until completion 1
• Additional risk factors for hepatitis requiring closer monitoring: daily alcohol use, chronic liver disease 1

Treatment Completion Criteria

Completion is based on total doses administered, not duration alone 1, 3:

• Daily isoniazid: at least 270 doses over 9 months (up to 12 months if interruptions occur) 1, 3
• Twice-weekly isoniazid: at least 76 doses over 9 months (up to 12 months if interruptions) 1
• Daily rifamycin plus pyrazinamide: at least 60 doses over 2 months (up to 3 months if interruptions) 1

Interrupted Therapy

When therapy is restored after interruption of ≥2 months, a medical examination to rule out TB disease is indicated before resuming treatment 1

Common Pitfalls and Caveats

• Do not use single-drug preventive therapy if active TB cannot be excluded - this risks creating drug resistance 2
• Do not combine rifampin with protease inhibitors or NNRTIs - significant drug interactions contraindicate this combination 1
• Do not routinely screen low-risk populations - the U.S. Preventive Services Task Force recommends testing only individuals at increased risk 6
• Do not assume completion based on time alone - verify total doses administered 1, 3
• Be vigilant for TB development even during preventive treatment - symptoms warrant immediate evaluation 7