Latent tuberculosis infection in children
- Lisa V Adams, MD
Lisa V Adams, MD
- Associate Professor
- Geisel School of Medicine at Dartmouth
- Jeffrey R Starke, MD
Jeffrey R Starke, MD
- Professor of Pediatrics
- Baylor College of Medicine
- Section Editors
- C Fordham von Reyn, MD
C Fordham von Reyn, MD
- Section Editor — Tuberculosis
- Section Editor — Nontuberculous Mycobacterial Infections
- Professor of Medicine
- Geisel School of Medicine at Dartmouth
- Morven S Edwards, MD
Morven S Edwards, MD
- Section Editor — Pediatric Infectious Diseases
- Professor of Pediatrics
- Baylor College of Medicine
Identification and treatment of children with latent tuberculosis infection (LTBI) has become an important component of tuberculosis (TB) control efforts in low incidence countries, such as the United States. The goals of TB screening programs are case finding and treatment of TB disease, prevention of development of disease, and decreased transmission.
Most children with LTBI have been infected recently (especially those younger than age five years). Children and adolescents are at higher risk for progression to TB disease (with potential for disseminated disease) than adults . Most cases of progression to TB disease occur within 2 to 12 months of initial infection . (See "Natural history, microbiology, and pathogenesis of tuberculosis".)
Issues related to diagnosis and treatment of LTBI in children will be reviewed here. Issues related to treatment of TB disease in children are discussed in detail separately. (See "Tuberculosis disease in children".)
Whom to test — In countries with low incidence and sufficient resources (such as the United States), testing for latent tuberculosis infection (LTBI) in children should be targeted to specific groups at risk for LTBI and/or progression to tuberculosis (TB) disease [3,4]. Only children who would benefit from treatment should be tested, so a decision to test presupposes a decision to treat if the test is positive.
In general, testing for LTBI is warranted to identify individuals who are at risk of new infection and to identify individuals at increased risk of reactivation due to associated conditions (form 1) [5,6]. Among children, the major risk factor for TB is contact with patients who have TB disease, either due to household exposure or residence in a region where TB is endemic (table 1). A child with a positive tuberculin skin test (TST) should prompt testing of the other siblings in the household. A questionnaire developed by the Pediatric Tuberculosis Collaborative Group can be used to screen children in a variety of clinical settings (form 1) . Additional risks include reactivation due to immunosuppressive conditions or medications. Children who will be receiving significant immunosuppressive therapy (particularly immunobiologic modulating agents) should be tested for LTBI before starting therapy .
- Targeted tuberculin testing and treatment of latent tuberculosis infection. American Thoracic Society. MMWR Recomm Rep 2000; 49:1.
- Cruz AT, Starke JR. Clinical manifestations of tuberculosis in children. Paediatr Respir Rev 2007; 8:107.
- Pediatric Tuberculosis Collaborative Group. Targeted tuberculin skin testing and treatment of latent tuberculosis infection in children and adolescents. Pediatrics 2004; 114:1175.
- Cruz AT, Starke JR, Lobato MN. Old and new approaches to diagnosing and treating latent tuberculosis in children in low-incidence countries. Curr Opin Pediatr 2014; 26:106.
- Wallis RS, Broder MS, Wong JY, et al. Granulomatous infectious diseases associated with tumor necrosis factor antagonists. Clin Infect Dis 2004; 38:1261.
- Bahçeciler NN, Nuhoglu Y, Nursoy MA, et al. Inhaled corticosteroid therapy is safe in tuberculin-positive asthmatic children. Pediatr Infect Dis J 2000; 19:215.
- Starke JR, Committee On Infectious Diseases. Interferon-γ release assays for diagnosis of tuberculosis infection and disease in children. Pediatrics 2014; 134:e1763.
- American Academy of Pediatrics. Tuberculosis. In: Red Book: 2012 Report of the Committee on Infectious Diseases, 29th ed, Pickering LK (Ed), American Academy of Pediatrics, Elk Grove Village, IL 2012.
- World Health Organization. Guidance for national tuberculosis programmes on the management of tuberculosis in children, Second edition. Geneva, Switzerland 2014. WHO/HTM/TB/2014.03
- Driver CR, Valway SE, Cantwell MF, Onorato IM. Tuberculin skin test screening in schoolchildren in the United States. Pediatrics 1996; 98:97.
- World Health Organization. Guidance for national tuberculosis programmes on the management of tuberculosis in children. Geneva, World Health Organization, 2006. WHO/HTM/TB/2006.371 and WHO/FCH/CAH/2006.7 http://whqlibdoc.who.int/hq/2006/WHO_HTM_TB_2006.371_eng.pdf (Accessed on February 11, 2013).
- World Health Organization. Treatment of Tuberculosis Guidelines, 4th edition. Geneva, World Health Organization, 2010. WHO/HTM/TB/2009.420 http://whqlibdoc.who.int/publications/2010/9789241547833_eng.pdf (Accessed on February 11, 2013).
- Saiman L, Aronson J, Zhou J, et al. Prevalence of infectious diseases among internationally adopted children. Pediatrics 2001; 108:608.
- Menzies D. Interpretation of repeated tuberculin tests. Boosting, conversion, and reversion. Am J Respir Crit Care Med 1999; 159:15.
- A World Atlas of BCG Vaccination Policies and Practices http://www.bcgatlas.org/ (Accessed on April 01, 2009).
- Mandalakas AM, Kirchner HL, Iverson S, et al. Predictors of Mycobacterium tuberculosis infection in international adoptees. Pediatrics 2007; 120:e610.
- Jacobs S, Warman A, Richardson R, et al. The tuberculin skin test is unreliable in school children BCG-vaccinated in infancy and at low risk of tuberculosis infection. Pediatr Infect Dis J 2011; 30:754.
- Starke JR. Interferon-gamma release assays for diagnosis of tuberculosis infection in children. Pediatr Infect Dis J 2006; 25:941.
- Detjen AK, Keil T, Roll S, et al. Interferon-gamma release assays improve the diagnosis of tuberculosis and nontuberculous mycobacterial disease in children in a country with a low incidence of tuberculosis. Clin Infect Dis 2007; 45:322.
- Lighter J, Rigaud M, Eduardo R, et al. Latent tuberculosis diagnosis in children by using the QuantiFERON-TB Gold In-Tube test. Pediatrics 2009; 123:30.
- Connell TG, Curtis N, Ranganathan SC, Buttery JP. Performance of a whole blood interferon gamma assay for detecting latent infection with Mycobacterium tuberculosis in children. Thorax 2006; 61:616.
- Nicol MP, Davies MA, Wood K, et al. Comparison of T-SPOT.TB assay and tuberculin skin test for the evaluation of young children at high risk for tuberculosis in a community setting. Pediatrics 2009; 123:38.
- Mandalakas AM, Detjen AK, Hesseling AC, et al. Interferon-gamma release assays and childhood tuberculosis: systematic review and meta-analysis. Int J Tuberc Lung Dis 2011; 15:1018.
- Machingaidze S, Wiysonge CS, Gonzalez-Angulo Y, et al. The utility of an interferon gamma release assay for diagnosis of latent tuberculosis infection and disease in children: a systematic review and meta-analysis. Pediatr Infect Dis J 2011; 30:694.
- Critselis E, Amanatidou V, Syridou G, et al. The effect of age on whole blood interferon-gamma release assay response among children investigated for latent tuberculosis infection. J Pediatr 2012; 161:632.
- Starke JR. Interferon-γ release assays for the diagnosis of tuberculosis infection in children. J Pediatr 2012; 161:581.
- Chiappini E, Bonsignori F, Mazzantini R, et al. Interferon-gamma release assay sensitivity in children younger than 5 years is insufficient to replace the use of tuberculin skin test in western countries. Pediatr Infect Dis J 2014; 33:1291.
- Debord C, De Lauzanne A, Gourgouillon N, et al. Interferon-gamma release assay performance for diagnosing tuberculosis disease in 0- to 5-year-old children. Pediatr Infect Dis J 2011; 30:995.
- Moyo S, Isaacs F, Gelderbloem S, et al. Tuberculin skin test and QuantiFERON® assay in young children investigated for tuberculosis in South Africa. Int J Tuberc Lung Dis 2011; 15:1176.
- Howley MM, Painter JA, Katz DJ, et al. Evaluation of QuantiFERON-TB gold in-tube and tuberculin skin tests among immigrant children being screened for latent tuberculosis infection. Pediatr Infect Dis J 2015; 34:35.
- Machingaidze S, Verver S, Mulenga H, et al. Predictive value of recent QuantiFERON conversion for tuberculosis disease in adolescents. Am J Respir Crit Care Med 2012; 186:1051.
- Comstock GW. How much isoniazid is needed for prevention of tuberculosis among immunocompetent adults? Int J Tuberc Lung Dis 1999; 3:847.
- Cruz AT, Starke JR. Increasing adherence for latent tuberculosis infection therapy with health department-administered therapy. Pediatr Infect Dis J 2012; 31:193.
- Lobato MN, Jereb JA, Starke JR. Unintended consequences: mandatory tuberculin skin testing and severe isoniazid hepatotoxicity. Pediatrics 2008; 121:e1732.
- Sterling TR, Villarino ME, Borisov AS, et al. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med 2011; 365:2155.
- Villarino ME, Scott NA, Weis SE, et al. Treatment for preventing tuberculosis in children and adolescents: a randomized clinical trial of a 3-month, 12-dose regimen of a combination of rifapentine and isoniazid. JAMA Pediatr 2015; 169:247.
- Villarino E, Scott N, Weis S, et al. Tolerability among children of three months of once-weekly rifapentine + INH (3HP) vs. 9 months of daily INH (9H) for treatment of latent tuberculosis infection: The PREVENT TB Study (TBTC Study 26/ACTG 5259), Abstract presented at IDSA’s IDWeek Annual meeting, San Diego, California, October 17–21, 2012.
- Centers for Disease Control and Prevention (CDC). Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat latent Mycobacterium tuberculosis infection. MMWR Morb Mortal Wkly Rep 2011; 60:1650.
- Finnell SM, Christenson JC, Downs SM. Latent tuberculosis infection in children: a call for revised treatment guidelines. Pediatrics 2009; 123:816.
- Whom to test
- - Case contacts (TST 5 mm cutoff)
- - Foreign-born (TST 10 mm cutoff)
- How to test
- - Tuberculin skin test
- - Interferon-gamma release assays
- RULING OUT TUBERCULOSIS DISEASE
- Isoniazid and rifapentine
- SUBSEQUENT MANAGEMENT
- SUMMARY AND RECOMMENDATIONS