Article Figures & Data
Tables
Active Latent Estimated numbers, 2012 Global2,4 8.6 million people per year; 1.3 million deaths per year 2 billion people United States7,9,10 9,945 tuberculosis cases (rate of 3.2 cases per 100,000 people) 10 to 15 million people Clinical presentation4,5 Usually symptomatic Asymptomatic Depends on primary disease, but usually includes persistent cough (>2 weeks); fever; night sweats; unexplained weight loss; fatigue; dyspnea; hemoptysis; chest pain; pleuritic pain Chest radiograph4,11 Usually abnormal radiographic imaging Normal radiographic imaging Depends on primary disease, but usually includes the following: If primary (recent) infection: middle or lower lobe infiltrates, ipsilateral hilar adenopathy, or cavitation
If secondary (reactivation) infection: upper lobe infiltrates or cavitation
If healed (previous) infection: hilar or upper lobe dense pulmonary nodules, with or without visible calcification
- Table 2. Key Differences Between Tuberculin Skin Test (TST) and Interferon-γ Release Assay (IGRA) as Diagnostic Measures for Latent Tuberculosis Infection
Characteristics TST IGRA Protocol23,30 After the 0.1-mL intradermal injection of PPD of Mycobacterium antigens into the patient, the area is measured between 48 to 72 hours for size of induration After taking a 3- to 5-mL sample of peripheral blood mononuclear cells from the patient, the response of IFN-γ production by T-lymphocytes upon stimulation with specific Mycobacterium tuberculosis antigens (CFP-10, ESAT-6, TB7.7) is measured within 24 hours Estimated sensitivity21,32 75% to 90% (reduced in immunocompromised patients) 78% to 92% Estimated specificity21,32 70% to 95% (reduced in BCG-vaccinated and NTM infections) 93% to 98% Advantages23,33 No laboratory procedures or costs May be more cost-effective Requires one visit Objectivity in test interpretation Disadvantages32 Requires follow-up visit (48 to 72 hours later) Requires laboratory procedures High subjectivity in test interpretation Should not be used in children <2 years of age because of limited data in children between 2 and 4 years of age BCG, Bacillus Calmette-Guérin; IFN, interferon; NTM, nontuberculous mycobacteria; PPD, purified protein derivative.
Medication Duration Dose Frequency Total Doses (n) Isoniazid 9 months Adults: 5 mg/kg Daily 270 Children: 10–20 mg/kg* Maximum dose: 300 mg Adults: 15 mg/kg Twice weekly by DOT 76 Children: 20–40 mg/kg* Maximum dose: 900 mg 6 months Adult: 5 mg/kg Daily 180 Children: Not recommended Maximum dose: 300 mg Adults: 15 mg/kg Twice weekly by DOT 52 Children: Not recommended Maximum dose: 900 mg Isoniazid and rifapentine 3 months Adults and children >12 years: Once weekly by DOT 12 INH†: 15 mg/kg rounded up to nearest 50 or 100 mg; 900 mg maximum RPT†: 10.0–14.0 kg: 300 mg
14.1–25.0 kg: 450 mg
25.1–32.0 kg: 600 mg
32.1–49.9 kg: 750 mg
≥50 kg: 900 mg maximum
Rifampin 4 months Adult: 10 mg/kg‡ Daily 120 Maximum dose: 600 mg ↵* The American Academy of Pediatrics recommended INH dosage.
↵† INH is formulated as 100- and 300-mg tablets. RPT is formulated as 150-mg tablets in blister packs that should be kept sealed until use.
↵‡ In the United States, the recommended latent tuberculosis infection treatment in children is a 9-month INH regimen. For latent tuberculosis infection treatment in infants, children, and adolescents when INH cannot be tolerated or the child has had contact with a patient infected with an INH-resistant but rifamycin-susceptible organism, the American Academy of Pediatrics recommends a 6-month daily rifampin dosage (180 dosages) of 10 to 20 mg/kg.
DOT, directly observed therapy; INH, isoniazid; RPT, rifapentine.
- Table 4. Key Diagnostic and Treatment Recommendations for Practice According to the Strength of Recommendations Taxonomy71
Clinical Recommendation Strength of Recommendation* References Sequential 2-step tuberculin skin tests should be performed in people who require baseline evaluations and have initial negative test results. C 21 Tuberculin skin tests are preferred over interferon-γ release assays as the diagnostic tool in children <5 years old. B 45 Interferon-γ release assays should be administered in adults, including BCG-vaccinated individuals or people with immunocompromising conditions. A 37, 38, 44 Interferon-γ release assays should be administered in hard-to-reach groups for prompt identification and management of LTBI. A 42, 45 Baseline laboratory values of hepatic enzyme levels should be performed in patients with HIV or underlying liver disease or in pregnant or postpartum women, in whom abnormal results should be evaluated routinely during LTBI therapy. B 58 Daily regimen of isoniazid for a duration of 9 months is the medication of choice for LTBI in adults and children. A 58 Equivalent therapeutic outcomes of a 12-dose regimen of isoniazid and rifapentine for a duration of 3 months, when compared with the daily regimen of isoniazid for a duration of 9 months, have demonstrated increased compliance. A 69, 70 ↵* Strength of recommendations: A = consistent and good quality patient-oriented evidence; B = inconsistent or limited quality patient-oriented evidence; C = consensus, usual practice, opinion, disease-oriented evidence, and case series for studies of diagnosis, treatment, prevention, or screening.
BCG, bacillus Calmette-Guérin; HIV, human immunodeficiency virus; LTBI, latent tuberculosis infection.
- Table 5. Take-Home Points on Specific Population Groups to Test for Latent Tuberculosis Infections (LTBIs)
Categories Population Groups Description High risk of exposure or infection with Mycobacterium tuberculosis10,12,58 Close contact Children, adolescents, or adults with close contact with high-risk adults Congregated living conditions Employees or residents of long-term care facilities, correctional facilities, homeless shelters Foreign born People who moved from countries with a high burden of TB to the United States (<5 years) High risk of LTBI progression to TB disease10,12,58 History of TB People acquiring latent TB infection within the previous 2 years or people with previous untreated/ineffective treatment of active TB with no sign of active TB at the time of starting latent TB treatment Age Children <4 years Substance use People who inject illicit drugs Immunosuppression People with poor nutrition status; previous surgical interventions (e.g., gastrointestinal surgical procedures); immunosuppressive medications (e.g., tumor necrosis factor-α antagonists, chronic corticosteroid use); immunocompromising conditions (e.g., HIV, chronic renal failure, diabetes mellitus, cancer) HIV, human immunodeficiency virus; TB, tuberculosis.
