Skip to main navigation menu Skip to main content Skip to site footer
##common.pageHeaderLogo.altText##

Review article: Biomedical intelligence

Vol. 144 No. 3738 (2014)

Novel concepts in the epidemiology, diagnosis and prevention of childhood tuberculosis

  • Nicole Ritz
  • Nigel Curtis
DOI
https://doi.org/10.4414/smw.2014.14000
Cite this as:
Swiss Med Wkly. 2014;144:w14000
Published
07.09.2014

Summary

Tuberculosis (TB) is one of the oldest diseases known to mankind, yet it is the second leading cause of death from an infection worldwide today. In the absence of epidemiological data, TB in children was not considered significant and research efforts did not prioritise this group. More recently, there has been renewed interest in childhood TB, leading to improved understanding of the fundamental differences between children and adults in relation to both TB infection and disease. Children with TB infection have a high risk of rapid progression to disease which leads to challenges in diagnosis but also offers the opportunity to investigate biomarkers for infection, progression and protection. This review discusses the most relevant advances in the understanding of epidemiology, diagnosis and prevention of children with TB. It also highlights challenges and research priorities in childhood TB, which include better diagnostic tests, accurate correlates of protection and an improved vaccine.

References

  1. Comas I, Coscolla M, Luo T, Borrell S, Holt KE, Kato-Maeda M, et al. Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans. Nat Genet. 2013;45(10):1176–82.
  2. World Health Organization. TB report. 2012 [cited 2013 14 Aug]; Available from: http://www.who.int/tb/publications/global_report/en/.
  3. Reichman LB. The U-shaped curve of concern. Am Rev Respir Dis. 1991;144(4):741–2.
  4. World Health Organization, Global Tuberculosis Report 2012, 2013.
  5. Sandgren A, Hollo V, Quinten C, Manissero D. Childhood tuberculosis in the European Union/European Economic Area, 2000 to 2009. Euro Surveill. 2011;16(12).
  6. Oesch Nemeth, G., Nemeth J, Altpeter E, Ritz N. Epidemiology of childhood tuberculosis in Switzerland between 1996 and 2011. Eur J of Pediatr. 2013; in press.
  7. Nendaz M, Perrier A. Diagnostic errors and flaws in clinical reasoning: mechanisms and prevention in practice. Swiss Med Wkly. 2012;142:w13706.
  8. Gengenbacher M, Kaufmann SH. Mycobacterium tuberculosis: success through dormancy. FEMS Microbiol Rev. 2012;36(3):514–32.
  9. Lawn SD, Wood R, Wilkinson RJ. Changing concepts of “latent tuberculosis infection” in patients living with HIV infection. Clin Dev Immunol. 2011. 2011.
  10. Young DB, Gideon HP, Wilkinson RJ. Eliminating latent tuberculosis. Trends Microbiol. 2009;17(5):183–8.
  11. Barry CE, 3rd, Boshoff HI, Dartois V, Dick T, Ehrt S, Flynn J, et al. The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat Rev Microbiol. 2009;7(12):845–55.
  12. Marais BJ, Gie RP, Hesseling AC, Schaaf HS, Lombard C, Enarson DA, et al. A refined symptom-based approach to diagnose pulmonary tuberculosis in children. Pediatrics. 2006;118(5):e1350–9.
  13. Hatherill M, Hanslo M, Hawkridge T, Little F, Workman L, Mahomed H, et al. Structured approaches for the screening and diagnosis of childhood tuberculosis in a high prevalence region of South Africa. Bull World Health Organ. 2010;88(4):312–20.
  14. Nejat S, Buxbaum C, Eriksson M, Pergert M, Bennet R. Pediatric tuberculosis in Stockholm: a mirror to the world. Pediatr Infect Dis J. 2012;31(3):224–7.
  15. Dodd LE, Wilkinson RJ. Diagnosis of paediatric tuberculosis: the culture conundrum. Lancet Infect Dis. 2013;13(1):3–4.
  16. Sarrazin H, Wilkinson KA, Andersson J, Rangaka MX, Radler L, van Veen K, et al. Association between tuberculin skin test reactivity, the memory CD4 cell subset, and circulating FoxP3–expressing cells in HIV-infected persons. J Infect Dis. 2009;199(5):702–10.
  17. Ritz N, Connell TG, Paxton GA, Buttery JP, Curtis N, Ranganathan SC. A three-way comparison of tuberculin skin testing, QuantiFERON-TB gold and T-SPOT.TB in children. PLoS ONE. 2008;3(7):e2624.
  18. Connell T, Tebruegge M, Ritz N, Curtis N. Interferon-gamma release assays for the diagnosis of tuberculosis. Pediatr Infect Dis J. 2009;28(8):758–9.
  19. Sun L, Xiao J, Miao Q, Feng WX, Wu XR, Yin QQ, et al. Interferon gamma release assay in diagnosis of pediatric tuberculosis: a meta-analysis. FEMS Immunol Med Microbiol. 2011;63(2):165–73.
  20. Walzl G, Ronacher K, Hanekom W, Scriba TJ, Zumla A. Immunological biomarkers of tuberculosis. Nat Rev Immunol. 2011;11(5):343–54.
  21. Chegou NN, Heyckendorf J, Walzl G, Lange C, Ruhwald M. Beyond the IFN-gamma horizon: Biomarkers for immunodiagnosis of infection with M. tuberculosis. Eur Respir J. 2013.
  22. Lighter J, Rigaud M, Huie M, Peng CH, Pollack H. Chemokine IP-10: an adjunct marker for latent tuberculosis infection in children. Int J Tuberc Lung Dis. 2009;13(6):731–6.
  23. Whittaker E, Gordon A, Kampmann B. Is IP-10 a better biomarker for active and latent tuberculosis in children than IFNgamma? PLoS One, 2008. 3(12): p. e3901.
  24. Ruhwald M, Petersen J, Kofoed K, Nakaoka H, Cuevas LE, Lawson L, et al. Improving T-cell assays for the diagnosis of latent TB infection: potential of a diagnostic test based on IP-10. PLoS One. 2008;3(8):e2858.
  25. Diel R, Loddenkemper R, Nienhaus A. Evidence-based comparison of commercial interferon-gamma release assays for detecting active TB: a metaanalysis. Chest. 2010;137(4):952–68.
  26. Machingaidze S, Wiysonge CS, Gonzalez-Angulo Y, Hatherill M, Moyo S, Hanekom W, 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(8):694–700.
  27. Mazurek GH, Jereb J, Vernon A, LoBue P, Goldberg S, Castro K. Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection – United States, 2010. MMWR Recomm Rep. 2010;59(RR-5):1–25.
  28. Lungenliga Schweiz, Handbuch Tuberkulose, 2011, Lungenliga Schweiz und Bundesamt für Gesundheit.
  29. National Institute for Health and Clinical Excellence Tuberculosis:Clinical diagnosis and management of tuberculosis, and measures for its prevention and control. 2011.
  30. Denkinger CM, Dheda K, Pai M. Guidelines on interferon-gamma release assays for tuberculosis infection: concordance, discordance or confusion? Clin Microbiol Infect. 2011;17(6):806–14.
  31. Connell TG, Tebruegge M, Ritz N, Bryant PA, Leslie D, Curtis N. Indeterminate interferon-gamma release assay results in children. Pediatr Infect Dis J. 2010;29(3):285–6.
  32. Thomas TA, Mondal D, Noor Z, Liu L, Alam M, Haque R, et al. Malnutrition and helminth infection affect performance of an interferon gamma-release assay. Pediatrics. 2010;126(6):e1522–9.
  33. Debord C, De Lauzanne A, Gourgouillon N, Guerin-El Khourouj V, Pedron B, Gaudelus J, et al. Interferon-gamma release assay performance for diagnosing tuberculosis disease in 0– to 5–year-old children. Pediatr Infect Dis J. 2011;30(11):995–7.
  34. World Health Organization Roadmap for childhood tuberculosis towards zero deaths. 2013.
  35. Trunz BB, Fine P, Dye C. Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness. Lancet. 2006;367(9517):1173–80.
  36. Hesseling AC, Marais BJ, Gie RP, Schaaf HS, Fine PE, Godfrey-Faussett P, et al. The risk of disseminated Bacille Calmette-Guerin (BCG) disease in HIV-infected children. Vaccine. 2007;25(1):14–8.
  37. Ritz N, Curtis N. Mapping the global use of different BCG vaccine strains. Tuberculosis (Edinb). 2009;89(4):248–51.
  38. Ritz N, Hanekom WA, Robins-Browne R, Britton WJ, Curtis N. Influence of BCG vaccine strain on the immune response and protection against tuberculosis. FEMS Microbiol Rev. 2008;32(5):821–41.
  39. Ritz N, Dutta B, Donath S, Casalaz D, Connell TG, Tebruegge M, et al. The influence of bacille Calmette-Guerin vaccine strain on the immune response against tuberculosis: a randomized trial. Am J Respir Crit Care Med. 2012;185(2):213–22.
  40. Favorov M, Ali M, Tursunbayeva A, Aitmagambetova I, Kilgore P, Ismailov S, et al. Comparative tuberculosis (TB) prevention effectiveness in children of Bacillus Calmette-Guerin (BCG) vaccines from different sources, Kazakhstan. PLoS ONE. 2012;7(3):e32567.
  41. Ritz N, Tebruegge M, Connell TG, Sievers A, Robins-Browne R, Curtis N. Susceptibility of Mycobacterium bovis BCG vaccine strains to antituberculous antibiotics. Antimicrob Agents Chemother. 2009;53(1):316–8.
  42. Dierig A, Tebruegge M, Krivec U, Heininger U, Ritz N. Current status of Bacille Calmette-Guérin (BCG) immunisation in Europe – a ptbnet survey, 2014: Abstract submitted: Annual meeting of the European Society for Paediatric Infectious Diseases.
  43. Flanagan KL, van Crevel R, Curtis N, Shann F, Levy O. Heterologous (“nonspecific”) and sex-differential effects of vaccines: epidemiology, clinical trials, and emerging immunologic mechanisms. Clin Infect Dis. 2013;57(2):283–9.
  44. Ritz N, CasalazD, Hanekom WA, Britton WJ, Dutta B, Donath S, et al. Reply: Bacille Calmette-Guerin vaccine: innate immunity and nonspecific effects. Am J Respir Crit Care Med. 2013;187(7):779–80.
  45. Gan C, Mostafid H, Khan MS, Lewis DJ. BCG immunotherapy for bladder cancer – the effects of substrain differences. Nat Rev Urol. 2013;10(10):580–8.
  46. Ritz N, Mui M, Balloch A, Curtis N. Non-specific effect of Bacille Calmette-Guerin vaccine on the immune response to routine immunisations. Vaccine. 2013;31(30):3098–103.
  47. Ota, M.O., J. Vekemans, S.E. Schlegel-Haueter, K. Fielding, M. Sanneh, M. Kidd, et al. Influence of Mycobacterium bovis bacillus Calmette-Guerin on antibody and cytokine responses to human neonatal vaccination. J Immunol. 2002;168(2):919–25.
  48. Roth A, Garly ML, Jensen H, Nielsen J, Aaby P. Bacillus Calmette-Guerin vaccination and infant mortality. Expert Rev Vaccines. 2006;5(2):277–93.
  49. Shann F. The non-specific effects of vaccines. Arch Dis Child. 2010;95(9):662–7.
  50. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998;393(6685):537–44.
  51. Behr MA, Wilson MA, Gill WP, Salamon H, Schoolnik GK, Rane S, et al. Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science. 1999;284(5419):1520–3.
  52. Tameris MD, Hatherill M, Landry BS, Scriba TJ, Snowden MA, Lockhart S, et al. Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial. Lancet. 2013.
  53. Lalvani A, Sridhar S, von Reyn CF. Tuberculosis vaccines: time to reset the paradigm? Thorax. 2013;68(12):1092–4.
  54. Bishai W, Sullivan Z, Bloom BR, Andersen P. Bettering BCG: a tough task for a TB vaccine? Nat Med. 2013;19(4):410–1.
  55. Kagina BM, Abel B, Scriba TJ, Hughes EJ, Keyser A, Soares A, et al. Specific T Cell Frequency and Cytokine Expression Profile do not Correlate with Protection against Tuberculosis, Following BCG Vaccination of Newborns. Am J Respir Crit Care Med. 2010;182(8):1073–9.
  56. Ritz N, Strach M, Yau C, Dutta B, Tebruegge M, Connell TG, et al. A comparative analysis of polyfunctional T cells and secreted cytokines induced by Bacille Calmette-Guerin immunisation in children and adults. PLoS ONE. 2012;7(7):e37535.
  57. Zufferey C, Germano S, Dutta B, Curtis N, Ritz N. The Contribution of Non-Conventional T Cells and NK Cells in the Mycobacterial-Specific IFNgamma Response in Bacille Calmette-Guerin (BCG)-Immunized Infants. PLoS ONE. 2013;8(10):e77334.
  58. Andersen P, Munk ME, Pollock JM, Doherty TM. Specific immune-based diagnosis of tuberculosis. Lancet. 2000;356(9235):1099–104.

Most read articles by the same author(s)