The Indian Journal of Pediatrics

, Volume 86, Issue 8, pp 740–745 | Cite as

Management of Latent Tuberculosis Infection in Children from Developing Countries

  • Agam Jain
  • Rakesh LodhaEmail author
Review Article


Tuberculosis (TB), once widely prevalent throughout the world, experienced falling incidence rates in early twentieth century in developed nations, even before the introduction of anti-TB drugs, attributed to improved hygiene and living conditions. Active TB may develop following fresh infection or activation of latent tuberculosis infection (LTBI). LTBI is a state of persistent bacterial viability, however, the host stays asymptomatic and there is no evidence of clinically active tuberculosis. Therefore, treatment of all LTBI is considered as one of the ways to control tuberculosis. Diagnosis of LTBI relies on presence of immune-reactivity to TB antigen and commonly used tests include tuberculin skin test and interferon gamma release assay (IGRA). At present there is no diagnostic test that can identify an individual with LTBI who will progress to develop active disease or remain asymptomatic. Therefore, it is unclear whom to treat. In the current scenario, treatment for LTBI is restricted to high risk groups which include under-5 y contacts of adults with pulmonary TB. Various regimens for treatment of LTBI are evolving and consist of isoniazid (INH) alone for 6–9 mo or combination of INH and rifampicin for 3–4 mo or once a week combination of rifapentin and INH for 3 mo. There is a need for research to identify LTBI, risk factors for progression of LTBI to active disease and a shorter regimen for treatment.


Interferon gamma assay INH prophylaxis IPT Rifapentin Tuberculin skin test 


Authors’ Contributions

AJ: Performed literature search and wrote manuscript; RL: Planned the literature search and was involved in manuscript writing. RL will act as guarantor for this paper.

Compliance with Ethical Standards

Conflict of Interest


Source of Funding



  1. 1.
    Getahun H, Matteelli A, Chaisson RE, Raviglione M. Latent Mycobacterium tuberculosis infection. N Engl J Med. 2015;372:2127–35.CrossRefPubMedGoogle Scholar
  2. 2.
    Russell DG. Mycobacterium tuberculosis and the intimate discourse of a chronic infection. Immunol Rev. 2011;240:252–68.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Pai M, Behr MA, Dowdy D, et al. Tuberculosis. Nat Rev Dis Primers. 2016;2:16076.CrossRefPubMedGoogle Scholar
  4. 4.
    Dodd PJ, Gardiner E, Coghlan R, Seddon JA. Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study. Lancet Glob Health. 2014;2:e453–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Houben RMGJ, Dodd PJ. The global burden of latent tuberculosis infection: a re-estimation using mathematical modelling. PLoS Med. 2016;13:e1002152.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    van Leth F, van der Werf MJ, Borgdorff MW. Prevalence of tuberculous infection and incidence of tuberculosis, a re-assessment of the Styblo rule. Bull World Health Org. 2008;86:20–6.CrossRefPubMedGoogle Scholar
  7. 7.
    WHO | WHO End TB Strategy [Internet]. WHO. Available at: Accessed 9 Sept 2018.
  8. 8.
    Getahun H, Kittikraisak W, Heilig CM, et al. Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies. PLoS Med [Internet]. 2011;8:18. Available at: Accessed 9 Sept 2018.
  9. 9.
    Nienhaus A, Ringshausen FC, Costa JT, Schablon A, Tripodi D. IFN-γ release assay versus tuberculin skin test for monitoring TB infection in healthcare workers. Expert Rev Anti-Infect Ther. 2013;11:37–48.CrossRefPubMedGoogle Scholar
  10. 10.
    Farhat M, Greenaway C, Pai M, Menzies D. False-positive tuberculin skin tests: what is the absolute effect of BCG and non-tuberculous mycobacteria? Int J Tuberc Lung Dis. 2006;10:1192–204.PubMedGoogle Scholar
  11. 11.
    Lockman S, Tappero JW, Kenyon TA, Rumisha D, Huebner RE, Binkin NJ. Tuberculin reactivity in a pediatric population with high BCG vaccination coverage. Int J Tuberc Lung Dis. 1999;3:23–30.PubMedGoogle Scholar
  12. 12.
    Dorman SE, Belknap R, Graviss EA, et al. Interferon-γ release assays and tuberculin skin testing for diagnosis of latent tuberculosis infection in healthcare workers in the United States. Am J Respir Crit Care Med. 2014;189:77–87.PubMedGoogle Scholar
  13. 13.
    WHO | Latent TB Infection : Updated and consolidated Guidelines for Programmatic Management [Internet]. WHO. Available at: Accessed 9 Sept 2018.
  14. 14.
    Akolo C, Adetifa I, Shepperd S, Volmink J. Treatment of latent tuberculosis infection in HIV infected persons. Cochrane Database Syst Rev. 2010;1:CD000171.Google Scholar
  15. 15.
    Zunza M, Gray DM, Young T, Cotton M, Zar HJ. Isoniazid for preventing tuberculosis in HIV-infected children. Cochrane Database Syst Rev. 2017;8:CD006418.PubMedGoogle Scholar
  16. 16.
    Badje A, Moh R, Gabillard D, et al. Effect of isoniazid preventive therapy on risk of death in west African, HIV-infected adults with high CD4 cell counts: long-term follow-up of the Temprano ANRS 12136 trial. Lancet Glob Health. 2017;5:e1080–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Comstock GW, Livesay VT, Woolpert SF. The prognosis of a positive tuberculin reaction in childhood and adolescence. Am J Epidemiol. 1974;99:131–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Zeidberg LD, Dillon A, Gass RS. Risk of developing tuberculosis among children of tuberculous parents. Am Rev Tuberc Pulm Dis. 1954;70:1009–19.CrossRefGoogle Scholar
  19. 19.
    Fox GJ, Barry SE, Britton WJ, Marks GB. Contact investigation for tuberculosis: a systematic review and meta-analysis. Eur Respir J. 2013;41:140–56.CrossRefPubMedGoogle Scholar
  20. 20.
    Morrison J, Pai M, Hopewell PC. Tuberculosis and latent tuberculosis infection in close contacts of people with pulmonary tuberculosis in low-income and middle-income countries: a systematic review and meta-analysis. Lancet Infect Dis. 2008;8:359–68.CrossRefPubMedGoogle Scholar
  21. 21.
    Diallo T, Adjobimey M, Ruslami R, et al. Safety and side effects of rifampin versus isoniazid in children. New Engl J Med. 2018;379:454–63.CrossRefPubMedGoogle Scholar
  22. 22.
    Zenner D, Beer N, Harris RJ, Lipman MC, Stagg HR, van der Werf MJ. Treatment of latent tuberculosis infection: an updated network meta-analysis. Ann Intern Med. 2017;167:248–55.CrossRefPubMedGoogle Scholar
  23. 23.
    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.CrossRefPubMedGoogle Scholar
  24. 24.
    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;169:247–55.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Balcells ME, Thomas SL, Godfrey-Faussett P, Grant AD. Isoniazid preventive therapy and risk for resistant tuberculosis. Emerg Infect Dis. 2006;12:744–51.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    den Boon S, Matteelli A, Getahun H. Rifampicin resistance after treatment for latent tuberculous infection: a systematic review and meta-analysis. Int J Tuberc Lung Dis. 2016;20:1065–71.CrossRefGoogle Scholar
  27. 27.
    Prajapati S, Upadhyay K, Mukherjee A, et al. High prevalence of primary drug resistance in children with intrathoracic tuberculosis in India. Paediatr Int Child Health. 2016;36:214–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Behr MA, Edelstein PH, Ramakrishnan L. Revisiting the timetable of tuberculosis. BMJ. 2018;362:k2738.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Dr. K C Chaudhuri Foundation 2019

Authors and Affiliations

  1. 1.Department of PediatricsAIIMSNew DelhiIndia

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