Tuberculosis disease 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; 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
Formal policies and control efforts addressing tuberculosis (TB) in children have been limited, in part due to lack of a standardized case definition and difficulties associated with establishing a definitive diagnosis . However, since diagnostic and treatment tools for TB in children have begun to improve significantly, TB in children has received increasing attention by researchers, clinicians, and policy makers.
Issues related to TB disease in children will be reviewed here. Issues related to diagnosis and treatment of latent TB infection in children are discussed in detail separately. (See "Latent tuberculosis infection in children".)
Global epidemiology — Estimating the global burden of tuberculosis (TB) disease in children is challenging due to the lack of a standard case definition, the difficulty in establishing a definitive diagnosis, the frequency of extrapulmonary disease in young children, and the relatively low public health priority given to TB in children relative to adults .
The World Health Organization (WHO) publishes global TB data including new and relapse cases by age. In its 2014 report, the WHO estimates that, of the nine million incident cases of TB in 2013, approximately 550,000 occurred among children under age 15 . Additionally, it estimated that there were 80,000 pediatric deaths due to TB (among HIV-uninfected children). Approximately 75 percent of these cases occurred in the 22 highest TB-burden countries (table 1) . In many developing countries, children compose more than one-half of the population, suggesting that the reported cases of childhood TB are likely underestimated.
Children under age five represent an important demographic group for understanding TB epidemiology, since TB frequently progresses rapidly from latent infection to disease, and severe disease manifestations, such as miliary TB and meningitis, are more common in this age group. Therefore, these children serve as sentinel cases, indicating recent and/or ongoing transmission in the community.
- Starke JR. New concepts in childhood tuberculosis. Curr Opin Pediatr 2007; 19:306.
- Nelson LJ, Wells CD. Global epidemiology of childhood tuberculosis. Int J Tuberc Lung Dis 2004; 8:636.
- World Health Organization. Global Tuberculosis Report 2014. http://www.who.int/tb/publications/global_report/en/ (Accessed on July 07, 2015).
- Marais BJ, Gie RP, Schaaf HS, et al. The clinical epidemiology of childhood pulmonary tuberculosis: a critical review of literature from the pre-chemotherapy era. Int J Tuberc Lung Dis 2004; 8:278.
- Jenkins HE, Tolman AW, Yuen CM, et al. Incidence of multidrug-resistant tuberculosis disease in children: systematic review and global estimates. Lancet 2014; 383:1572.
- Centers for Disease Control and Prevention. Tuberculosis: Slide Set - Epidemiology of Pediatric Tuberculosis in the United States, 1993-2012. http://www.cdc.gov/tb/publications/slidesets/pediatrictb/d_link_text.htm (Accessed on July 20, 2015).
- Winston CA, Menzies HJ. Pediatric and adolescent tuberculosis in the United States, 2008-2010. Pediatrics 2012; 130:e1425.
- Centers for Disease Control and Prevention (CDC). Trends in tuberculosis--United States, 2010. MMWR Morb Mortal Wkly Rep 2011; 60:333.
- Cruz AT, Starke JR. Clinical manifestations of tuberculosis in children. Paediatr Respir Rev 2007; 8:107.
- Perez-Velez CM, Marais BJ. Tuberculosis in children. N Engl J Med 2012; 367:348.
- Stop TB Partnership Childhood TB Subgroup World Health Organization. Guidance for National Tuberculosis Programmes on the management of tuberculosis in children. Chapter 1: introduction and diagnosis of tuberculosis in children. Int J Tuberc Lung Dis 2006; 10:1091.
- Schaaf HS, Beyers N, Gie RP, et al. Respiratory tuberculosis in childhood: the diagnostic value of clinical features and special investigations. Pediatr Infect Dis J 1995; 14:189.
- Mulenga H, Tameris MD, Luabeya KK, et al. The Role of Clinical Symptoms in the Diagnosis of Intrathoracic Tuberculosis in Young Children. Pediatr Infect Dis J 2015; 34:1157.
- Mandalakas AM, Starke JR. Current concepts of childhood tuberculosis. Semin Pediatr Infect Dis 2005; 16:93.
- World Health Organization, Childhood TB Subgroup. Guidance for national tuberculosis programmes on the management of tuberculosis in children, Geneva. WHO/HTM/ TB/2006.371WHO/FCH/CAH/2006.7.
- Starke JR. Tuberculosis in childhood and pregnancy. In: Tuberculosis: current concepts and treatment, 2nd ed, Friedman LN (Ed), CRC Press, Boca Raton 2000.
- Hageman J, Shulman S, Schreiber M, et al. Congenital tuberculosis: critical reappraisal of clinical findings and diagnostic procedures. Pediatrics 1980; 66:980.
- Manji KP, Msemo G, Tamim B, Thomas E. Tuberculosis (presumed congenital) in a neonatal unit in Dar-es-Salaam, Tanzania. J Trop Pediatr 2001; 47:153.
- Laibl VR, Sheffield JS. Tuberculosis in pregnancy. Clin Perinatol 2005; 32:739.
- Cruz AT, Hwang KM, Birnbaum GD, Starke JR. Adolescents with tuberculosis: a review of 145 cases. Pediatr Infect Dis J 2013; 32:937.
- American Academy of Pediatrics. Tuberculosis. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.805.
- Pereira L. Tuberculosis: role of etiologic diagnosis and tuberculin skin test. Pediatr Pulmonol Suppl 2004; 26:240.
- Drobac PC, Shin SS, Huamani P, et al. Risk factors for in-hospital mortality among children with tuberculosis: the 25-year experience in Peru. Pediatrics 2012; 130:e373.
- Targeted tuberculin testing and treatment of latent tuberculosis infection. American Thoracic Society. MMWR Recomm Rep 2000; 49:1.
- Hatherill M, Hawkridge T, Zar HJ, et al. Induced sputum or gastric lavage for community-based diagnosis of childhood pulmonary tuberculosis? Arch Dis Child 2009; 94:195.
- Steiner P, Rao M, Victoria MS, et al. Persistently negative tuberculin reactions: their presence among children with culture positive for Mycobacterium tuberculosis (tuberculin-negative tuberculosis). Am J Dis Child 1980; 134:747.
- van den Bos F, Terken M, Ypma L, et al. Tuberculous meningitis and miliary tuberculosis in young children. Trop Med Int Health 2004; 9:309.
- van der Weert EM, Hartgers NM, Schaaf HS, et al. Comparison of diagnostic criteria of tuberculous meningitis in human immunodeficiency virus-infected and uninfected children. Pediatr Infect Dis J 2006; 25:65.
- Ge L, Ma JC, Han M, et al. Interferon-γ release assay for the diagnosis of latent Mycobacterium tuberculosis infection in children younger than 5 years: a meta-analysis. Clin Pediatr (Phila) 2014; 53:1255.
- Menzies D, Pai M, Comstock G. Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research. Ann Intern Med 2007; 146:340.
- Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med 2008; 149:177.
- 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.
- Mazurek GH, Jereb J, Lobue P, et al. Guidelines for using the QuantiFERON-TB Gold test for detecting Mycobacterium tuberculosis infection, United States. MMWR Recomm Rep 2005; 54:49.
- Starke J. Use of the new TB test in children should be limited. AAP News 2006; 27:14.
- Gie RP, Beyers N, Schaaf HS, Goussard P. The challenge of diagnosing tuberculosis in children: a perspective from a high incidence area. Paediatr Respir Rev 2004; 5 Suppl A:S147.
- Gwee A, Pantazidou A, Ritz N, et al. To x-ray or not to x-ray? Screening asymptomatic children for pulmonary TB: a retrospective audit. Arch Dis Child 2013; 98:401.
- Marais BJ, Gie RP, Hesseling AC, et al. Radiographic signs and symptoms in children treated for tuberculosis: possible implications for symptom-based screening in resource-limited settings. Pediatr Infect Dis J 2006; 25:237.
- Lighter J, Rigaud M. Diagnosing childhood tuberculosis: traditional and innovative modalities. Curr Probl Pediatr Adolesc Health Care 2009; 39:61.
- Centers for Disease Control and Prevention (CDC). Updated guidelines for the use of nucleic acid amplification tests in the diagnosis of tuberculosis. MMWR Morb Mortal Wkly Rep 2009; 58:7.
- Zar HJ, Hanslo D, Apolles P, et al. Induced sputum versus gastric lavage for microbiological confirmation of pulmonary tuberculosis in infants and young children: a prospective study. Lancet 2005; 365:130.
- Marais BJ, Gie RP, Schaaf HS, et al. Childhood pulmonary tuberculosis: old wisdom and new challenges. Am J Respir Crit Care Med 2006; 173:1078.
- Lobato MN, Loeffler AM, Furst K, et al. Detection of Mycobacterium tuberculosis in gastric aspirates collected from children: hospitalization is not necessary. Pediatrics 1998; 102:E40.
- Mukherjee A, Singh S, Lodha R, et al. Ambulatory gastric lavages provide better yields of Mycobacterium tuberculosis than induced sputum in children with intrathoracic tuberculosis. Pediatr Infect Dis J 2013; 32:1313.
- Cruz AT, Revell PA, Starke JR. Gastric Aspirate Yield For Children With Suspected Pulmonary Tuberculosis. J Pediatric Infect Dis Soc 2013; 2:171.
- Starke JR. Pediatric tuberculosis: time for a new approach. Tuberculosis (Edinb) 2003; 83:208.
- Owens S, Abdel-Rahman IE, Balyejusa S, et al. Nasopharyngeal aspiration for diagnosis of pulmonary tuberculosis. Arch Dis Child 2007; 92:693.
- Nicol MP, Workman L, Isaacs W, et al. Accuracy of the Xpert MTB/RIF test for the diagnosis of pulmonary tuberculosis in children admitted to hospital in Cape Town, South Africa: a descriptive study. Lancet Infect Dis 2011; 11:819.
- Smith MS, Williams DE, Worley SD. Potential uses of combined halogen disinfectants in poultry processing. Poult Sci 1990; 69:1590.
- Marcy O, Ung V, Goyet S, et al. Performance of Xpert MTB/RIF and Alternative Specimen Collection Methods for the Diagnosis of Tuberculosis in HIV-Infected Children. Clin Infect Dis 2016; 62:1161.
- Tebruegge M, Ritz N, Curtis N, Shingadia D. Diagnostic Tests for Childhood Tuberculosis: Past Imperfect, Present Tense and Future Perfect? Pediatr Infect Dis J 2015; 34:1014.
- Bates M, O'Grady J, Maeurer M, et al. Assessment of the Xpert MTB/RIF assay for diagnosis of tuberculosis with gastric lavage aspirates in children in sub-Saharan Africa: a prospective descriptive study. Lancet Infect Dis 2013; 13:36.
- Zar HJ, Workman L, Isaacs W, et al. Rapid molecular diagnosis of pulmonary tuberculosis in children using nasopharyngeal specimens. Clin Infect Dis 2012; 55:1088.
- Held M, Laubscher M, Mears S, et al. Diagnostic Accuracy of the Xpert MTB/RIF Assay for Extrapulmonary Tuberculosis in Children With Musculoskeletal Infections. Pediatr Infect Dis J 2016; 35:1165.
- Solomons RS, Visser DH, Friedrich SO, et al. Improved diagnosis of childhood tuberculous meningitis using more than one nucleic acid amplification test. Int J Tuberc Lung Dis 2015; 19:74.
- Perez-Velez CM. Pediatric tuberculosis: new guidelines and recommendations. Curr Opin Pediatr 2012; 24:319.
- 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
- Seddon JA, Furin JJ, Gale M, et al. Caring for children with drug-resistant tuberculosis: practice-based recommendations. Am J Respir Crit Care Med 2012; 186:953.
- World Health Organization. The use of molecular line probe assays for the detection of resistance to second-line antituberculosis drugs: Policy guidance. WHO, Geneva 2016. http://www.who.int/tb/WHOPolicyStatementSLLPA.pdf?ua=1 (Accessed on May 23, 2016).
- Anderson ST, Kaforou M, Brent AJ, et al. Diagnosis of childhood tuberculosis and host RNA expression in Africa. N Engl J Med 2014; 370:1712.
- Donald PR, Maher D, Maritz JS, Qazi S. Ethambutol dosage for the treatment of children: literature review and recommendations. Int J Tuberc Lung Dis 2006; 10:1318.
- Cruz AT, Starke JR. Treatment of tuberculosis in children. Expert Rev Anti Infect Ther 2008; 6:939.
- Török ME, Yen NT, Chau TT, et al. Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)--associated tuberculous meningitis. Clin Infect Dis 2011; 52:1374.
- Thampi N, Stephens D, Rea E, Kitai I. Unexplained deterioration during antituberculous therapy in children and adolescents: clinical presentation and risk factors. Pediatr Infect Dis J 2012; 31:129.
- Olive C, Mouchet F, Toppet V, et al. Paradoxical reaction during tuberculosis treatment in immunocompetent children: clinical spectrum and risk factors. Pediatr Infect Dis J 2013; 32:446.
- World Health Organization. WHO treatment guidelines for drug-resistant tuberculosis: 2016 update. WHO, Geneva 2016. http://www.who.int/tb/MDRTBguidelines2016.pdf?ua=1 (Accessed on May 17, 2016).
- Centers for Disease Control and Prevention. Provisional CDC guidelines for the use and safety monitoring of bedaquiline fumarate (Sirturo) for the treatment of multidrug-resistant tuberculosis. MMWR Recomm Rep 2013; 62:1.
- Seddon JA, Hesseling AC, Godfrey-Faussett P, Schaaf HS. High treatment success in children treated for multidrug-resistant tuberculosis: an observational cohort study. Thorax 2014; 69:458.
- Drobac PC, Mukherjee JS, Joseph JK, et al. Community-based therapy for children with multidrug-resistant tuberculosis. Pediatrics 2006; 117:2022.
- Chiang SS, Starke JR, Miller AC, et al. Baseline Predictors of Treatment Outcomes in Children With Multidrug-Resistant Tuberculosis: A Retrospective Cohort Study. Clin Infect Dis 2016; 63:1063.
- Ettehad D, Schaaf HS, Seddon JA, et al. Treatment outcomes for children with multidrug-resistant tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis 2012; 12:449.
- Global epidemiology
- United States epidemiology
- CLINICAL MANIFESTATIONS
- Pulmonary tuberculosis
- Extrapulmonary tuberculosis
- Perinatal infection
- Adolescent infection
- Screening tests
- - Tuberculin skin test
- - Interferon-gamma release assays
- - Chest radiography
- - Computed tomography scan
- Laboratory studies
- - Acid-fast bacilli smear and culture
- Gastric aspirate
- Other specimens
- - Xpert MTB/RIF and other rapid tests
- Drug resistance
- Investigational diagnostic methods
- Susceptible disease
- Drug-resistant TB
- SUMMARY AND RECOMMENDATIONS