> Table of Contents > TUBERCULOSIS, LATENT (LTBI)
TUBERCULOSIS, LATENT (LTBI)
Kay A. Bauman, MD, MPH
image BASICS
DESCRIPTION
  • Latent tuberculosis infection (LTBI) is an asymptomatic, noninfectious condition that follows exposure to an active case of tuberculosis. It is usually detected by a positive skin test (i.e., purified protein derivative [PPD]), positive interferon-&ggr; release assay (IGRA) test. In LTBI, acid-fast bacilli smear and culture are negative, and chest x-ray (CXR) does not suggest active TB.
  • Tuberculosis (TB) is a common infection transmitted by inhaling airborne bacilli from a person with active TB. The bacilli multiply in the alveoli and are carried by macrophages, lymphatics, and blood to distant sites (e.g., lung, pleura, brain, kidney, bone).
  • Active TB occurs in 5-10% of infected individuals not receiving preventive therapy. Chance of active TB increases with immunosuppression and is highest for all individuals within 2 years of infection; 85% of the cases are pulmonary, which spreads person-to-person via an aerosol route.
  • The majority (66% in 2014) of active TB cases in the United States occur in foreign-born persons. Most are as the result of reactivation of LTBI (1). Active TB cases continue to decline but at a slower rate than in previous years.
  • LTBI treatment is a key component of the TB elimination strategy of the United States.
EPIDEMIOLOGY
  • High-risk groups include immigrants from Asia, Latin America, Africa, and the Pacific basin; homeless persons; persons with a history of drug use or history of incarceration; HIV-infected individuals; and health care workers.
  • Also at high risk are those who are newly exposed (particularly children). In 2014, there were 9,412 new cases of TB in the United States (1).
  • In 2014, Asians had the highest active TB case rate of all groups, 28.5 times the rate in whites. The rate of TB in Hispanics and in non-Hispanic blacks is 8 times higher than for whites (1).
  • Of active TB cases in 2013 in ethnic minorities, 95% of Asian cases, 75% of Hispanic cases, 40% of black cases, and 23% of white cases were foreign-born (1). This highlights the need to screen foreign-born persons for latent TB and treat those with positive screening tests.
  • In 2014, 55.3% of foreign-born persons with TB came from five countries: Mexico (20.6%), Philippines (12.1%), Vietnam (8.1%), India (7.7%), and China (6.8%) (1).
  • In 2014, 6% of active TB cases in the United States were in HIV-positive individuals, 5% were homeless, 4% were incarcerated, and 2% in long-term care facilities (1).
Prevalence
  • 4% of the U.S. population has LTBI.
  • 1/3 of the world's population is estimated to harbor latent TB.
  • Predominant gender: male > female
ETIOLOGY AND PATHOPHYSIOLOGY
Mycobacterium tuberculosis, Mycobacterium bovis, and Mycobacterium africanum
RISK FACTORS
  • HIV infection, immunosuppression
  • Immigrants (from Asia, Africa, Latin America, Pacific Islands, or area with high rate of TB), including migrant workers
  • Close contact with infected individual
  • Institutionalization (e.g., prison, nursing home)
  • Use of illicit drugs
  • Lower socioeconomic status or homeless
  • Health care workers
  • Chronic medical disease such as diabetes mellitus (DM), end-stage renal disease, cancer, or silicosis; organ transplant (immunosuppression)
  • Persons with fibrotic changes on CXR consistent with previous TB infection (2)
  • Recent TB skin test (TST) converters (2)
  • Laboratory personnel working with mycobacteria
GENERAL PREVENTION
Screen for LTBI and treat individuals with positive tests.
COMMONLY ASSOCIATED CONDITIONS
  • HIV infection (see “Initial Tests (lab, imaging)”)
  • Immunosuppression
image DIAGNOSIS
PHYSICAL EXAM
No active signs of infection on exam in patients with LTBI
DIFFERENTIAL DIAGNOSIS
Fungal infections; atypical mycobacteria or Nocardia
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • None routinely recommended
  • In higher risk patients: liver profile, hepatitis C virus (HCV), and hepatitis B virus (HBV) screening
  • HIV test recommended to assess risk for active TB in men who have sex with men or persons with a history of IV drug use
  • CXR to rule out active TB
  • CT scan of the chest has good sensitivity (rarely needed).
Diagnostic Procedures/Other
  • Tuberculin Skin Test (TST): PPD: 5 U (0.1 mL) intermediate-strength intradermal volar forearm. Measure induration at 48 to 72 hours:
    • Positive if induration is
      • >5 mm and patient has HIV infection (or suspected) (2), is immunosuppressed, had recent close TB contact, or has clinical evidence of active or old disease on CXR
      • > 10 mm and patient age <4 years or has other risk factors noted earlier
      • > 15 mm and patient age >4 years and has no risk factors (2)
    • Negative if induration <5 mm on initial test and, if indicated, on second test
    • Use the two-step test (administer a second intradermal test 1 to 3 weeks after initial test; measure and interpret as usual) if patient has had no recent PPD and is age >55 years or is a nursing home resident, prison inmate, or health care worker.
    • Preferred for children <5 years.
  • The interferon gamma release assays (IGRA) QuantiFERON-TB and QuantiFERON-TB GOLD; T-SPOT measure the release of interferon by sensitized lymphocytes when exposed to antigens of M. tuberculosis. It is unaffected by prior BCG vaccination, requires only one visit, and has improved sensitivity and specificity but is costly (3).
  • Special considerations
    • Steroids: false-negative skin test
    • Measles vaccine: May suppress tuberculin activity; simultaneous PPD and measles vaccine recommended; if not simultaneous, defer PPD 4 to 6 weeks after measles vaccine.
    • The multiple-puncture tine test is not recommended.
    • Do not use history of BCG vaccination to ignore a positive PPD in adults and forego treatment.
    • Disorders that may alter results and give a falsenegative skin test:
      • Recent viral infection
      • New (< 10 weeks) infection
      • Severe malnutrition; HIV; anergy
      • Age <6 months
      • Overwhelming TB
image TREATMENT
GENERAL MEASURES
  • Must exclude active TB
  • Treatment for LTBI is crucial to control and eliminate TB disease in the United States. LTBI treatment decreases the risk of active TB in those treated and decreases risks of potential spread to others (2).
  • Treat LTBI at any age if patient has HIV, has had close TB contact, is a recent converter (<2 years), is an IV drug user, has an abnormal CXR, has a high-risk medical condition, or is in another highrisk group.
  • Directly observed therapy (DOT) is recommended if patient adherence is not assured
    • Use isoniazid (INH) (for 9 months).
    • Acceptable alternative: INH for 6 months
    • Use INH 900 mg and rifapentine 900 mg weekly for 12 weeks.
  • P.1071

  • Treat LTBI during pregnancy if patient has recent infection or is HIV positive (use INH with pyridoxine, and monitor liver enzymes); otherwise, treatment may be postponed until after delivery (2).
  • Consult with public health or ID for HIV infection and suspected INH resistance (2).
  • Note: Because of severe side effects associated with rifampin and pyrazinamide, these medications are less often recommended for LTBI treatment (2).
  • Exclusions: cirrhosis, active hepatitis, history of excessive alcohol consumption (2)
MEDICATION
  • INH alone
    • INH-scored tablets: 100 mg, 300 mg, or syrup 10 mg/mL
      • Daily: adult 300 mg; pediatric 10 to 15 mg/kg (maximum 300 mg)
      • Twice weekly: adult 900 mg; pediatric 20 to 30 mg/kg (maximum 900 mg)
      • Treatment for 9 months; typical completion rates of ≤60%
      • Precautions
        • Follow liver function if the patient has history of alcoholism, HBV, HCV, or other liver dysfunction or new signs of liver injury.
        • INH: Peripheral neuritis and hypersensitivity are possible. Consider pyridoxine.
        • INH: An idiosyncratic drug reaction that results in INH-associated severe liver injury was reported by the CDC in 17 patients from 2004 to 2008. Monitoring patients on treatment is recommended, looking for symptoms of liver injury (4).
  • INH and rifapentine
    • Patients >12 years: rifapentine, a rifampin-like drug can be used to treat LTBI. 900 mg weekly (if patient >50 kg) and INH, 15 to 25 mg/kg weekly (rounded to nearest 50 or 100 mg; 900 mg max) for 12 weeks given as direct observation therapy. This new and shorter treatment has increased rates of completion compared with 9 months of INH (82% compared with 69% in one trial), slightly more adverse effects (4.9% vs. 3.7%), and is more costly.
      • Contraindications to INH/rifapentine: HIV patients receiving antiretroviral therapy, pregnancy. Rifapentine may cause hyperuricemia and hematuria (5).
  • Alternative: rifampin alone
    • Adults 600 mg/day for 4 months; children 10 to 20 mg/kg/day for 6 months (max 600 mg/day). Fewer data exist for efficacy of this regimen but can be considered for contacts of INH-resistant TB or patient with INH contraindications. In one study, the 4-month course increased compliance from 62.6% with INH to 71.6% with rifampin (6).
ADDITIONAL THERAPIES
Pediatric Considerations
  • Follow public health recommendations for assessing and treating newborn with mother/household contact with infection or disease.
  • If mother or household contact has LTBI, skin test all household contacts, and treat any with positive PPD.
  • If contact has abnormal CXR, separate infant until infectious status is known; if not contagious, monitor infant PPD (7).
  • If mother has disease and is possibly contagious, evaluate infant for congenital TB and test for HIV; separate newborn until mother is noninfectious (7).
  • Treat suspected congenital TB.
  • If no congenital disease, start INH and repeat PPD after 3 to 4 months. If positive, reassess infant and finish 9 months of INH. If PPD is negative and source is noninfectious, stop INH and monitor infant (7).
  • BCG vaccine, live-attenuated M. bovis: used more commonly in developing countries in children to prevent complications of TB
INPATIENT CONSIDERATIONS
Geriatric Considerations
  • Before entering a chronic care facility, patients should have a PPD using two-step protocols.
  • INH side effects are more pronounced.
Discharge Criteria
  • Activity, as tolerated
  • No isolation required.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • During preventive therapy for LTBI: initial monthly visits to assess adherence to regimen and to monitor for hepatitis and neuropathy; if stable, can monitor less frequently
  • If patient remains asymptomatic, repeat of CXR is not needed.
  • Check liver enzymes if patient is symptomatic, is HIV positive, has chronic liver disease, uses alcohol, or is pregnant or postpartum, and modify drugs, if needed.
DIET
Regular. Consider pyridoxine, 10 to 50 mg/day.
PROGNOSIS
  • Generally, there are few complications and treatment is effective if medications are taken as prescribed.
  • Retreatment is not necessary.
REFERENCES
1. Scott C, Kirkling HL, Jeffries C, et al. Tuberculosis trends—United States, 2014. MMWR Morb Mortal Wkly Rep. 2015;64(10):265-269.
2. Jensen PA, Lambert LA, Iademarco MF, et al. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR Recomm Rep. 2005;54(RR-17):1-141.
3. Campos-Outcalt D. When, and when not, to use the interferon-gamma TB test. J Fam Pract. 2005;54(10):873-875.
4. Centers for Disease Control and Prevention. Severe isoniazid-associated liver injuries among persons being treated for latent tuberculosis infection— United States, 2004-2008. MMWR Morb Mortal Wkly Rep. 2010;59(8):224-229.
5. Centers for Disease Control and Prevention. Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat latent Mycobacterium tuberculosis infection. MMWR Morb Mortal Wkly Rep. 2011;60(48):1650-1653.
6. Page KR, Sifakis F, Montes de Oca R, et al. Improved adherence and less toxicity with rifampin vs isoniazid for treatment of latent tuberculosis: a retrospective study. Arch Intern Med. 2006;166(17):1863-1870.
7. American Academy of Pediatrics. Red Book: 2003 Report of the Committee on Infectious Diseases. 26th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2003.
Additional Reading
&NA;
  • Latent Tuberculosis Infections: A guide for primary health care providers. http://www.cdc.gov/tb/publications/ltbi/treatment.htm. Accessed 2015.
  • Young DB, Gideon HP, Wilkinson RJ. Eliminating latent tuberculosis. Trends Microbiol. 2009;17(5): 183-188.
See Also
&NA;
Tuberculosis; Tuberculosis, Miliary
Codes
&NA;
ICD10
R76.11 Nonspecific reaction to skin test w/o active tuberculosis
Clinical Pearls
&NA;
  • An estimated 4% of the U.S. population have LTBI. Treatment of LTBI is crucial to control and eliminate TB disease in the United States.
  • Test household contacts of PPD-positive patients.
  • History of BCG vaccination, especially >10 years before PPD testing, should not be considered as the cause of a positive PPD. The interferon-&ggr; blood test is unaffected by prior BCG vaccination.
  • Treat all HIV-positive patients with LTBI with a prophylactic regimen.
  • Screen foreign-born persons for latent TB, and treat those who are positive.