Skip to main content

Advertisement

Log in

Latent Tuberculosis in Children: Diagnosis and Management

  • Symposium on Pediatric Tuberculosis
  • Published:
The Indian Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Control of tuberculosis in children often escapes attention because of the paucibacillary nature of the illness. However, they contribute much of the morbidity, mortality and future reservoir of the disease which reiterates the importance of risk-factor based screening for latent infection and appropriate treatment. We review the modalities and importance of diagnosis and treatment of latent tuberculosis infection in children. At this time, the role for interferon-gamma release assays in low-income, high-burden settings is rather limited but further research in the coming years might clear their role in children. An important emerging area of research is the development of an improved skin test for TB that uses specific mycobacterial antigens rather than tuberculin, thus is more feasible and useful in resource limited settings.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Amberson JB. The significance of latent forms of tuberculosis. N Engl J Med. 1938;219:572–6.

    Article  Google Scholar 

  2. Pediatric Tuberculosis Collaborative Group. Targeted tuberculin skin testing and treatment of latent tuberculosis infection in children and adolescents. Pediatrics. 2004;114:1175–201.

    Article  Google Scholar 

  3. Centers for Disease Control and Prevention. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care facilities. MMWR Recomm Rep. 1994;43:1–132.

    Google Scholar 

  4. Chugh S. Paediatric tuberculosis and DOTS strategy under RNTCP. J Indian Med Assoc. 2008;106:799–802.

    PubMed  Google Scholar 

  5. Working Group on Tuberculosis, Indian Academy Of Pediatrics (IAP). Consensus statement on childhood tuberculosis. Indian Pediatr. 2010;47:41–55.

    Article  Google Scholar 

  6. Marais BJ, Gie RP, Schaaf HS, Beyers N, Donald PR, Starke JR. Childhood pulmonary tuberculosis: old wisdom and new challenges. Am J Respir Crit Care Med. 2006;173:1078–90.

    Article  PubMed  Google Scholar 

  7. 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;61:616–20.

    Article  PubMed  CAS  Google Scholar 

  8. Dogra S, Narang P, Mendiratta DK, et al. Comparison of a whole blood interferon-gamma assay with tuberculin skin testing for the detection of tuberculosis infection in hospitalized children in rural India. J Infect. 2007;54:267–76.

    Article  PubMed  Google Scholar 

  9. Marais BJ, Pai M. New approaches and emerging technologies in the diagnosis of childhood tuberculosis. Paediatr Respir Rev. 2007;8:124–33.

    Article  PubMed  Google Scholar 

  10. Joint Statement of the American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC). Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000;161:S221–47.

    Google Scholar 

  11. Enarson DA. Use of the tuberculin skin test in children. Paediatr Respir Rev. 2004;5:S135–7.

    Article  PubMed  Google Scholar 

  12. 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;149:177–84.

    PubMed  Google Scholar 

  13. Lighter J, Rigaud M, Eduardo R, Peng CH, Pollack H. Latent tuberculosis diagnosis in children by using the QuantiFERON-TB Gold In-Tube test. Pediatrics. 2009;123:30–7.

    Article  PubMed  Google Scholar 

  14. Liebeschuetz S, Bamber S, Ewer K, et al. Diagnosis of tuberculosis in South African children with a T-cell-based assay: a prospective cohort study. Lancet. 2004;364:2196–203.

    Article  PubMed  CAS  Google Scholar 

  15. 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;45:322–8.

    Article  PubMed  CAS  Google Scholar 

  16. Zellweger JP. Latent tuberculosis: which test in which situation? Swiss Med Wkly. 2008;138:31–7.

    PubMed  Google Scholar 

  17. Ciaschetti A, Franchi A, Richeldi L, et al. Screening of latent tuberculosis infection in health care workers by QuantiFERON-TB and tuberculin skin test. G Ital Med Lav Ergon. 2007;29:406–7.

    PubMed  CAS  Google Scholar 

  18. Bakir M, Millington KA, Soysal A, et al. Prognostic value of a T cell-based, interferon-gamma biomarker in children with tuberculosis contact. Ann Intern Med. 2008;149:777–87.

    PubMed  Google Scholar 

  19. Diel R, Loddenkemper R, Meywald-Walter K, Gottschalk R, Nienhaus A. Comparative performance of tuberculin skin test, QuantiFERON-TB-Gold In Tube assay, and T-Spot.TB test in contact investigations for tuberculosis. Chest. 2009;135:1010–8.

    Article  PubMed  Google Scholar 

  20. Nakaoka H, Lawson L, Squire SB, et al. Risk for tuberculosis among children. Emerg Infect Dis. 2006;12:1383–8.

    PubMed  Google Scholar 

  21. Ewer K, Deeks J, Alvarez L, et al. Comparison of T-cell-based assay with tuberculin skin test for diagnosis of Mycobacterium tuberculosis infection in a school tuberculosis outbreak. Lancet. 2003;361:1168–73.

    Article  PubMed  Google Scholar 

  22. Hill PC, Brookes RH, Fox A, et al. Large-scale evaluation of enzyme-linked immunospot assay and skin test for diagnosis of Mycobacterium tuberculosis infection against a gradient of exposure in The Gambia. Clin Infect Dis. 2004;38:966–73.

    Article  PubMed  CAS  Google Scholar 

  23. Hill PC, Brookes RH, Adetifa IM, et al. Comparison of enzyme-linked immunospot assay and tuberculin skin test in healthy children exposed to Mycobacterium tuberculosis. Pediatrics. 2006;117:1542–8.

    Article  PubMed  Google Scholar 

  24. 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;123:38–43.

    Article  PubMed  Google Scholar 

  25. Pai M, O’Brien R. Tuberculosis diagnostics trials: do they lack methodological rigor? Expert Rev Mol Diagn. 2006;6:509–14.

    Article  PubMed  Google Scholar 

  26. Ranganathan S, Connell T, Curtis N. Interferon-gamma release assays in children–no better than tuberculin skin testing? J Infect. 2007;54:412–3.

    Article  PubMed  Google Scholar 

  27. Naseer A, Naqvi S, Kampmann B. Evidence for boosting Mycobacterium tuberculosis-specific IFN-gamma responses at 6 weeks following tuberculin skin testing. Eur Respir J. 2007;29:1282–3.

    Article  PubMed  CAS  Google Scholar 

  28. Bergamini BM, Losi M, Vaienti F, et al. Performance of commercial blood tests for the diagnosis of latent tuberculosis infection in children and adolescents. Pediatrics. 2009;123:419–24.

    Article  Google Scholar 

  29. Arend SM, Franken WP, Aggerbeck H, et al. Double-blind randomized Phase I study comparing rdESAT-6 to tuberculin as skin test reagent in the diagnosis of tuberculosis infection. Tuberculosis. 2008;88:249–61.

    Article  PubMed  CAS  Google Scholar 

  30. Nelson LJ, Jereb JA, Castro KG. New guidelines about latent tuberculosis infection in children and adolescents: a welcome advancement. Pediatrics. 2004;114:1084–6.

    Article  PubMed  Google Scholar 

  31. American Thoracic Society. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR Recomm Rep. 2000;49:1–51.

    Google Scholar 

  32. Mount FW, Ferebee SH. Preventive effects of isoniazid in the treatment of primary tuberculosis in children. N Engl J Med. 1961;265:713–21.

    Article  PubMed  CAS  Google Scholar 

  33. Comstock GW, Hammes LM, Pio A. Isoniazid prophylaxis in Alaskan Boarding schools. A comparison of two doses. Am Rev Respir Dis. 1969;100:773–9.

    PubMed  CAS  Google Scholar 

  34. Ferebee SH. Controlled chemoprophylaxis trials in tuberculosis. A general review. Bibl Tuberc. 1970;26:28–106.

    PubMed  CAS  Google Scholar 

  35. Stein MT, Liang D. Clinical hepatotoxicity of isoniazid in children. Pediatrics. 1979;64:499–505.

    PubMed  CAS  Google Scholar 

  36. O’Brien RJ, Long MW, Cross FS, Lyle MA, Snider Jr DE. Hepatotoxicity from isoniazid and rifampin among children treated for tuberculosis. Pediatrics. 1983;72:491–9.

    PubMed  Google Scholar 

  37. Finnell SM, Christenson JC, Downs SM. Latent tuberculosis infection in children: a call for revised treatment guidelines. Pediatrics. 2009;123:816–22.

    Article  PubMed  Google Scholar 

  38. Villarino ME, Ridzon R, Weismuller PC, et al. Rifampin preventive therapy for tuberculosis infection: experience with 157 adolescents. Am J Respir Crit Care Med. 1997;155:1735–8.

    PubMed  CAS  Google Scholar 

  39. Ormerod LP. Rifampicin and isoniazid prophylactic chemotherapy for tuberculosis. Arch Dis Child. 1998;78:169–71.

    Article  PubMed  CAS  Google Scholar 

  40. Nakajo MM, Rao M, Steiner P. Incidence of hepatotoxicity in children receiving isoniazid chemoprophylaxis. Pediatr Infect Dis J. 1989;8:649–50.

    PubMed  CAS  Google Scholar 

  41. Joint Tuberculosis Committee of the British Thoracic Society. Chemotherapy and management of tuberculosis in the United Kingdom: recommendations 1998. Thorax. 1998;53:536–48.

    Article  Google Scholar 

  42. Spyridis NP, Spyridis PG, Gelesme A, et al. The effectiveness of a 9 month regimen of isoniazid alone versus 3- and 4-month regimens of isoniazid plus rifampin for treatment of latent tuberculosis infection in children: results of an 11-year randomized study. Clin Infect Dis. 2007;45:715–22.

    Article  PubMed  CAS  Google Scholar 

  43. Magdorf K, Arizzi-Rusche AF, Geiter LJ, O’Brien RJ, Wahn U. Compliance and tolerance of new antitubercular short-term chemopreventive regimens in childhood–a pilot project. Pneumologie. 1994;48:761–4.

    PubMed  CAS  Google Scholar 

  44. Prevention CDC. Update: Adverse event data and Revised American Thoracic Society/CDC recommendations against the use of rifampin and pyrazinamide for treatment of latent tuberculosis infection—United States, 2003.

  45. Indian Academy of Pediatrics. Treatment of childhood tuberculosis: Consensus Statement of IAP Working Group. Indian Pediatr. 1997;34:1093–6.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Arushi Gahlot Saini.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Singh, M., Saini, A.G., Anil, N. et al. Latent Tuberculosis in Children: Diagnosis and Management. Indian J Pediatr 78, 464–468 (2011). https://doi.org/10.1007/s12098-010-0295-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12098-010-0295-7

Keywords

Navigation