Tijdschrift voor Kindergeneeskunde

, Volume 74, Issue 1, pp 30–36 | Cite as

De diagnostiek en behandeling van latente tuberculose-infectie in kinderen

  • N A. H. van Hest
  • R. van Altena
  • S. M. Arend
  • H. W. M. Baars
  • J. H. van Loenhout-Rooyackers
  • N. G. Hartwig
Tuberculose in Nederland


More often than active tuberculosis disease children have latent tuberculosis infection (ltbi), which can occur after contact with a patient suffering from smear-positive pulmonary tuberculosis, usually an adult household member. In young children the infection is almost always recently acquired. Compared to adults, infected children, especially children with an immune disorder, have an increased risk of progression to active tuberculosis disease, and will more frequently develop severe manifestations of tuberculosis, such as tuberculous meningitis or miliary tuberculosis. Treatment of ltbi considerably reduces the risk of progression to active disease. Most infected children are identified during contact investigations or immigration screening and treated by the Department of Tuberculosis Control of the Municipal Health Service. The tuberculin skin test is not always a reliable method to diagnose ltbi, particularly in children with a previous bcg vaccination or in children with a reduced immune response. Recently developed interferon-? tests may contribute to improved diagnosis of ltbi in the future. On account of the publication of new guidelines for diagnosis and treatment of ltbi in children in the United States as well as in the Netherlands, the policies and developments in the Netherlands are discussed.


Vaker dan de actieve ziekte tuberculose krijgen kinderen een latente tuberculose-infectie (ltbi), die optreedt na contact met een patiënt met open tuberculose, gewoonlijk een volwassen familielid. Bij jonge kinderen is de infectie vrijwel altijd recent. In vergelijking met volwassenen hebben geïnfecteerde kinderen, zeker die met een immuunstoornis, een verhoogd risico op het ontwikkelen van de ziekte tuberculose, en worden vaker ernstige vormen van tuberculose gezien zoals meningitis tuberculosa of miliaire tuberculose. Behandeling van ltbi reduceert de kans op progressie naar de actieve ziekte sterk. Meestal worden geïnfecteerde kinderen gevonden tijdens een contactonderzoek of bij een immigratiescreening en behandeld door de afdeling Tuberculosebestrijding van de ggd. De mantouxtest is niet altijd betrouwbaar om een ltbi vast te stellen, zeker niet bij kinderen die met bcg zijn gevaccineerd of bij kinderen met een verzwakte cellulaire afweer. Onlangs ontwikkelde interferon-?-tests kunnen in de toekomst helpen de diagnostiek van ltbi te verbeteren. Naar aanleiding van het verschijnen van de nieuwe Amerikaanse richtlijnen voor de diagnostiek en behandeling van ltbi bij kinderen en de nieuwe Nederlandse richtlijn behandeling ltbi worden beleid en ontwikkelingen in Nederland besproken.


  1. KNCV Tuberculosefonds. Index tuberculosis 2001–2002. Den Haag: KNCV Tuberculosefonds, 2005.Google Scholar
  2. Geuns HA van, Meijer J, Styblo K. Results of contact examination in Rotterdam, 1967–1969. Bull Int Union Tuberc 1975;50:107-21.PubMedGoogle Scholar
  3. Smith KC. Tuberculosis in children. Curr Probl Pediatr 2001;31:5-30.CrossRefGoogle Scholar
  4. Pediatric Tuberculosis Collaborative Group. Targeted tuberculin skin testing and treatment of latent tuberculosis infection in children and adolescents. Pediatrics 2004;114;1175-201.CrossRefGoogle Scholar
  5. Miller FJW, Scale ME, Taylor NM. Tuberculosis in children. Boston: Little, Brown, 1963.Google Scholar
  6. Altena R van. Tuberculosebehandeling nieuwe stijl. In: Jongste JC de, Groot R de, Verduin CM, red. Behandelingsstrategieën bij kinderen met luchtweginfecties. Houten: Bohn Stafleu Van Loghum, 1999.Google Scholar
  7. American Thoracic Society. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:S221-47.CrossRefGoogle Scholar
  8. Commissie voor Praktische Tuberculosebestrijding. De tuberculine huidtest. Den Haag: KNCV Tuberculosefonds, 2001.Google Scholar
  9. Verver S. Epidemiology of tuberculosis among immigrants in the Netherlands and in a high incidence area in South Africa [Thesis]. Amsterdam: Universiteit van Amsterdam, 2004.Google Scholar
  10. Andersen P, Munk ME, Pollock JM, et al. Specific immune-based diagnosis of tuberculosis. Lancet 2000;356:1099-104.CrossRefGoogle Scholar
  11. Arend, SM. Cellular immune responses to mycobacteria: towards specific immunodiagnosis and protection [Thesis]. Leiden: Leids Universitair Medisch Centrum, 2002.Google Scholar
  12. Mori T, Sakatani M, Yamagishi F, et al. Specific detection of tuberculosis infection: an interferon-gamma-based assay using new antigens. Am J Respir Crit Care Med 2004;170:59-64.CrossRefGoogle Scholar
  13. Brock I, Weldingh K, Leyten EM, et al. Specific T-cell epitopes for immunoassay-based diagnosis of Mycobacterium tuberculosis infection. J Clin Microbiol 2004;42:2379-87.CrossRefGoogle Scholar
  14. Barnes PF. Diagnosing latent tuberculosis infection: turning glitter to gold. Am J Respir Crit Care Med 2004;170:5-6.CrossRefGoogle Scholar
  15. Lalvani A, Pathan AA, Durkan H, et al. Enhanced contact tracing and spatial tracking of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells. Lancet 2001;357:2017-21.CrossRefGoogle Scholar
  16. 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.CrossRefGoogle Scholar
  17. Chapman AL, Munkanta M, Wilkinson KA, et al. Rapid detection of active and latent tuberculosis infection in HIV-positive individuals by enumeration of Mycobacterium tuberculosis-specific T cells. AIDS 2002;16:2285-93.CrossRefGoogle Scholar
  18. 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.CrossRefGoogle Scholar
  19. Centers for Disease Control and Prevention. Guidelines for using the QuantiFERON-TB test for diagnosing latent Mycobacterium tuberculosis infection. MMWR Recomm Rep 2003;52(RR-II):15-8.Google Scholar
  20. Joint Tuberculosis Committee of the British Thoracic Society. Chemotherapy and management of tuberculosis in the United Kingdom: recommendations 1998. Thorax 1998;53:536-48.CrossRefGoogle Scholar
  21. Centers for Disease Control and Prevention. 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. MMWR Morb Mortal Wkly Rep 2003;52:735-9.Google Scholar
  22. Comstock GW. How much isoniazid is needed for prevention of tuberculosis among immunocompetent adults? Int J Tuberc Lung Dis 1999;3:847-50.PubMedGoogle Scholar
  23. International Union against Tuberculosis Committee on Prophylaxis. Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five year of follow-up in the IUAT trial. Bull World Health Organ 1982;60:555-64.PubMedCentralGoogle Scholar
  24. Comstock GW, Hammes LM, Pio A. Isoniazid prophylaxis in Alaskan boarding schools: a comparison of two doses. Am Rev Resp Dis 1969;100:773-9.PubMedGoogle Scholar
  25. Mount FW, Ferrebee SH. Preventive effects of isoniazid in the treatment of primary tuberculosis in children. N Engl J Med 1961;265:713-21.CrossRefGoogle Scholar
  26. Ena J, Valls V. Short-course therapy with rifampin plus isoniazid, compared with standard therapy with isoniazid, for latent tuberculosis infection: A meta-analysis. Clin Infect Dis 2005;40:670-6.CrossRefGoogle Scholar
  27. Ormerod LP. Rifampicin and isoniazid prophylactic chemotherapy for tuberculosis. Arch Dis Child 1998;78:169-71.CrossRefGoogle Scholar
  28. Reichman LB, Lardizabal A, Hayden CH. Considering the role of four months of rifampin in the treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2004;170:832-5.CrossRefGoogle Scholar
  29. Menzies D, Dion MJ, Rabinovitch B, et al. Treatment completion and costs of a randomized trial of rifampin for 4 months versus isoniazid for 9 months. Am J Respir Crit Care Med 2004:15;170:445-9.CrossRefGoogle Scholar
  30. Villarino ME, Ridzon R, Weismuller PC, et al. Rifampicine preventive therapy for tuberculosis infection: experience with 157 adolescents. Am J Resp Crit Care Med 1997;155:1735-8.CrossRefGoogle Scholar
  31. Kopanoff DE, Snider DE, Caras GJ. Isoniazid-related hepatitis: a United States Public Health Service Cooperative Surveillance Study. Am Rev Respir Dis 1978;117:991-1001.PubMedGoogle Scholar
  32. Starke JR, Correa AG. Management of mycobacterial infection and disease in children. Pediatr Infect Dis J 1995;14:455-70.CrossRefGoogle Scholar
  33. Ormerod LP. Reduced incidence of tuberculosis by prophylactic chemotherapy in subjects showing strong reactions to tuberculin testing. Arch Dis Child 1987;62:1005-8.CrossRefGoogle Scholar
  34. Jasmer RM, Saukkonen JJ, Blumberg HM, et al. Short-course rifampin and pyrazinamide compared with isoniazid for latent tuberculosis infection: a multicenter clinical trial. Ann Intern Med 2002;137:640-7.CrossRefGoogle Scholar
  35. Hest R van, Baars H, Kik S, et al. Hepatotoxicity of rifampin-pyrazinamide and isoniazid preventive therapy and tuberculosis treatment. Clin Infect Dis 2004;39:488-96.CrossRefGoogle Scholar
  36. Magdorf K, Arizzi-Rusche AF, Geiter LJ, et al. Compliance and tolerance of new antitubercular short-term chemopreventive regimens in childhood-a pilot project [in German]. Pneumologie 1994;48:761-4.PubMedGoogle Scholar
  37. American Academy of Paediatrics. Tuberculosis. In: Red Book: Report of the Committee on Infectious Diseases, 25th ed. Elk Groove Village: American Academy of Paediatrics, 2000.Google Scholar
  38. Centers for Disease Control and Prevention. Management of persons exposed to multi-drug tuberculosis. MMWR Morb Mort Wkly Rep 1992;41(RR-II):61-71.Google Scholar
  39. Passanante MR, Gallagher CT, Reichman LB. Preventive therapy for contacts of multi-drug resistant tuberculosis. Chest 1994;106:431-4.CrossRefGoogle Scholar
  40. Trebucq A. Should ethambutol be recommended for routine treatment of tuberculosis in children? A review of the literature. Int J Tuberc Lung Dis 1997;1:12-5.PubMedGoogle Scholar

Copyright information

© Bohn Stafleu van Loghum 2006

Authors and Affiliations

  • N A. H. van Hest
    • 1
  • R. van Altena
    • 1
  • S. M. Arend
    • 1
  • H. W. M. Baars
    • 1
  • J. H. van Loenhout-Rooyackers
    • 1
  • N. G. Hartwig
    • 1
  1. 1.

Personalised recommendations