Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 25, Number 4—April 2019

Cost-effectiveness of Latent Tuberculosis Infection Screening before Immigration to Low-Incidence Countries

Jonathon R. Campbell, James C. Johnston, Victoria J. Cook, Mohsen Sadatsafavi, R. Kevin Elwood, and Fawziah MarraComments to Author 
Author affiliations: University of British Columbia, Vancouver, British Columbia, Canada (J.R. Campbell, J.C. Johnston, V.J. Cook, M. Sadatsafavi, R.K. Elwood, F. Marra); British Columbia Centre for Disease Control, Vancouver (J.C. Johnston, V.J. Cook, R.K. Elwood)

Main Article

Table 2

Model parameter estimates and values used for sensitivity analyses of intervention strategies for screening and treatment of latent TB infection in immigrants*

Parameter Estimate Range evaluated in PSA PSA distribution References
Screening parameters
TST sensitivity 0.782 0.69–0.87 Beta(43,12) (19)
TST specificity, no BCG 0.974 0.963–0.982 Beta(770,21) (20,21)
TST specificity, BCG 0.602 0.561–0.642 Beta(239,158) (20,21)
IGRA sensitivity 0.889 0.688–0.993 Beta(8,1) (19)
IGRA specificity 0.957 0.946–0.968 Beta(900,40) (20,21)
IGRA indeterminate† 0.06 0.05–0.07 Beta(83,1286) (21)
Complete TST‡ 1 Fixed Fixed
Complete medical evaluation§

Population characteristics¶
LTBI prevalence
Very high incidence 0.3162 0.2686–0.3880 Varied with reactivation rate (12,1517)
High incidence 0.2016 0.1706–0.2464 Varied with reactivation rate (12,1517)
Moderate incidence 0.0902 0.0763–0.1102 Varied with reactivation rate (12,1517)
Low incidence 0.0159 0.0135–0.0195 Varied with reactivation rate (12,1517)
Abnormal chest radiograph results or previous TB
Very high incidence 0.039 Fixed Fixed (15)
High incidence 0.028 Fixed Fixed (15)
Moderate incidence 0.029 Fixed Fixed (15)
Low incidence 0.008 Fixed Fixed (15)
Adherence to postarrival follow-up#
Treatment parameters
Initiate** 0.938 0.907–0.964 Beta(180.83,11.95) (5)
Complete, INH 0.616 0.561–0.670 Beta(131.66,82.07) (5)
Complete, RIF 0.814 0.745–0.876 Beta(76.85,17.56) (5)
Adverse event, INH 0.049 0.044–0.055 Beta(249,4789) (24,25)
Adverse event, RIF 0.021 0.018–0.025 Beta(109,4877) (24,25)
Adverse event hospitalization 0.01 0.0005–0.03 Beta(1,99) (25)
Death, INH 0.00000988 0–0.00002 Beta(2,202495) (26)
LTBI risk reduction, INH 0.90 0.78–0.95 Normal(−2.3,0.5)†† (27)
LTBI risk reduction, RIF 0.90 0.63–0.97 Normal(−2.3,0.8)†† (28,24)
Partial risk reduction, INH 0.346 0.267–0.490 Combination of normal distributions††, ‡‡ Expert opinion, (25)
Partial risk reduction, RIF 0.30 0.17–0.40 Normal(−0.35,0.1)†† Expert opinion, (24,28)
Adverse event duration
7 d
Expert opinion, (25)
TB parameters
Death from TB 0.0476 0.0391–0.0566 Beta(76,1523) (3)
Reactivation rate 0.0011 0.0009–0.0013 Beta(90.92,82545.55) (1517)
Abnormal CXR risk change 3.9 3.0–4.9 Normal(1.36,0.15)†† (29)
Extended therapy 0.124 0.029–0.264 Beta(2.366,16.713) Expert opinion, (30)
Relapse rate 0.0359 0.0197–0.0654 Normal(−3.327,0.365)†† (30)
Hospitalization duration
17 d
Expert opinion, (30)
Model parameters
BCG vaccination, <30 cases 0.605 0.60–0.61 Beta(45137,29502) (12,13)
BCG vaccination, ≥30 cases 0.998 0.997–0.999 Beta(185381,384) (12,13)
BCG vaccination uptake 0.837 Fixed Fixed (14)
Discount rate 0.03 Fixed Fixed (23)
Time horizon 25 y Fixed Fixed NA

*AE, adverse event; BCG, bacillus Calmette-Guérin; IGRA, interferon-gamma release assay; INH, isoniazid; LTBI, latent tuberculosis infection; NA, not available; PSA, probabilistic sensitivity analysis; RIF, rifampin; TST, tuberculin skin test; TB, tuberculosis.
†Treated as a negative result if it occurred; was equally likely to occur in those with and without LTBI.
‡Without being mandatory, this value is 63.5% (imputed from 43.4% completing screening when 68.4% adhere with a follow-up appointment) (5).
§Without being mandatory, this value is 78% (imputed from 43.7 of 56 individuals completing medical evaluation) (5).
¶Very high incidence, >200 cases/100,000; high incidence, >100 and <200 cases/100,000; moderate incidence, >30 and <100 cases/100,000; low incidence, <30 cases/100,000.
#From a meta-analysis (22); see also Appendix (
**This model assumes all who report postarrival due to a positive preimmigration LTBI diagnostic test are offered treatment. Exploratory analysis adjusts this assumption so that only the number who would complete TST screening begin treatment.
††Results from this distribution are exponentiated.
‡‡Formula: 0.33 × (Normal(−1.168,0.228)) + 0.374 × (Normal(−0.381,0.169)) + 0.293 × 1.

Main Article

  1. World Health Organization. Framework towards tuberculosis elimination in low-incidence countries. Geneva: The Organization; 2014 [cited 2018 Mar 7].
  2. Pareek  M, Greenaway  C, Noori  T, Munoz  J, Zenner  D. The impact of migration on tuberculosis epidemiology and control in high-income countries: a review. BMC Med. 2016;14:48. DOIPubMedGoogle Scholar
  3. Public Health Agency of Canada. Canadian tuberculosis standards, 7th ed. Ottawa (ON): Government of Canada; 2014 [cited 2018 Mar 7].
  4. Taylor  Z, Nolan  CM, Blumberg  HM; American Thoracic Society; Centers for Disease Control and Prevention; Infectious Diseases Society of America. Controlling tuberculosis in the United States. Recommendations from the American Thoracic Society, CDC, and the Infectious Diseases Society of America. MMWR Recomm Rep. 2005;54(RR-12):181.PubMedGoogle Scholar
  5. Alsdurf  H, Hill  PC, Matteelli  A, Getahun  H, Menzies  D. The cascade of care in diagnosis and treatment of latent tuberculosis infection: a systematic review and meta-analysis. Lancet Infect Dis. 2016;16:126978. DOIPubMedGoogle Scholar
  6. Campbell  J, Marra  F, Cook  V, Johnston  J. Screening immigrants for latent tuberculosis: do we have the resources? CMAJ. 2014;186:2467. DOIPubMedGoogle Scholar
  7. Campbell  JR, Sasitharan  T, Marra  F. A systematic review of studies evaluating the cost utility of screening high-risk populations for latent tuberculosis infection. Appl Health Econ Health Policy. 2015;13:32540. DOIPubMedGoogle Scholar
  8. Pareek  M, Baussano  I, Abubakar  I, Dye  C, Lalvani  A. Evaluation of immigrant tuberculosis screening in industrialized countries. Emerg Infect Dis. 2012;18:14229. DOIPubMedGoogle Scholar
  9. Institute of Medicine (US) Committee on the Elimination of Tuberculosis in the United States. Ending neglect: the elimination of tuberculosis in the United States. Geiter L, editor. Washington (DC): National Academies Press; 2000.
  10. Coker  R, van Weezenbeek  KL. Mandatory screening and treatment of immigrants for latent tuberculosis in the USA: just restraint? Lancet Infect Dis. 2001;1:2706. DOIPubMedGoogle Scholar
  11. Karnon  J, Stahl  J, Brennan  A, Caro  JJ, Mar  J, Möller  J; ISPOR-SMDM Modeling Good Research Practices Task Force. Modeling using discrete event simulation: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force—4. Value Health. 2012;15:8217. DOIPubMedGoogle Scholar
  12. Statistics Canada. Report on the demographic situation in Canada: permanent and temporary immigration to Canada from 2012 to 2014. Ottawa (ON): Government of Canada; 2016 [cited 2018 Mar 7].
  13. Badar  S, Araújo  T, Zwerling  A, Pai  M. BCG world atlas. 2nd edition. 2017 [cited 2018 Mar 7].
  14. World Health Organization. UNICEF. WHO-UNICEF estimates of BCG coverage. Geneva: World Health Organization; 2017 [cited 2018 Mar 7].
  15. Khan  K, Hirji  MM, Miniota  J, Hu  W, Wang  J, Gardam  M, et al. Domestic impact of tuberculosis screening among new immigrants to Ontario, Canada. CMAJ. 2015;187:E47381. DOIPubMedGoogle Scholar
  16. Campbell  JR, Chen  W, Johnston  J, Cook  V, Elwood  K, Krot  J, et al. Latent tuberculosis infection screening in immigrants to low-incidence countries: a meta-analysis. Mol Diagn Ther. 2015;19:10717. DOIPubMedGoogle Scholar
  17. Shea  KM, Kammerer  JS, Winston  CA, Navin  TR, Horsburgh  CR Jr. Estimated rate of reactivation of latent tuberculosis infection in the United States, overall and by population subgroup. Am J Epidemiol. 2014;179:21625. DOIPubMedGoogle Scholar
  18. Walter  ND, Painter  J, Parker  M, Lowenthal  P, Flood  J, Fu  Y, et al.; Tuberculosis Epidemiologic Studies Consortium. Persistent latent tuberculosis reactivation risk in United States immigrants. Am J Respir Crit Care Med. 2014;189:8895.PubMedGoogle Scholar
  19. Campbell  JR, Krot  J, Elwood  K, Cook  V, Marra  F. A systematic review on TST and IGRA tests used for diagnosis of LTBI in immigrants. Mol Diagn Ther. 2015;19:924. DOIPubMedGoogle Scholar
  20. 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;146:34054. DOIPubMedGoogle Scholar
  21. 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;149:17784. DOIPubMedGoogle Scholar
  22. Chan  IHY, Kaushik  N, Dobler  CC. Post-migration follow-up of migrants identified to be at increased risk of developing tuberculosis at pre-migration screening: a systematic review and meta-analysis. Lancet Infect Dis. 2017;17:7709. DOIPubMedGoogle Scholar
  23. Sanders  GD, Neumann  PJ, Basu  A, Brock  DW, Feeny  D, Krahn  M, et al. Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses. JAMA. 2016;316:1093103. DOIPubMedGoogle Scholar
  24. Menzies  D, Adjobimey  M, Ruslami  R, Trajman  A, Sow  O, Kim  H, et al. Four months of rifampin or nine months of isoniazid for latent tuberculosis in adults. N Engl J Med. 2018;379:44053. DOIPubMedGoogle Scholar
  25. Campbell  JR, Johnston  JC, Sadatsafavi  M, Cook  VJ, Elwood  RK, Marra  F. Cost-effectiveness of post-landing latent tuberculosis infection control strategies in new migrants to Canada. PLoS One. 2017;12:e0186778. DOIPubMedGoogle Scholar
  26. Salpeter  SR. Fatal isoniazid-induced hepatitis. Its risk during chemoprophylaxis. West J Med. 1993;159:5604.PubMedGoogle Scholar
  27. International Union Against Tuberculosis Committee on Prophylaxis. Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. Bull World Health Organ. 1982;60:55564.PubMedGoogle 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;170:8325. DOIPubMedGoogle Scholar
  29. Aldridge  RW, Zenner  D, White  PJ, Williamson  EJ, Muzyamba  MC, Dhavan  P, et al. Tuberculosis in migrants moving from high-incidence to low-incidence countries: a population-based cohort study of 519 955 migrants screened before entry to England, Wales, and Northern Ireland. Lancet. 2016;388:25108. DOIPubMedGoogle Scholar
  30. Holland  DP, Sanders  GD, Hamilton  CD, Stout  JE. Costs and cost-effectiveness of four treatment regimens for latent tuberculosis infection. Am J Respir Crit Care Med. 2009;179:105560. DOIPubMedGoogle Scholar
  31. Jasmer  RM, Bozeman  L, Schwartzman  K, Cave  MD, Saukkonen  JJ, Metchock  B, et al.; Tuberculosis Trials Consortium. Recurrent tuberculosis in the United States and Canada: relapse or reinfection? Am J Respir Crit Care Med. 2004;170:13606. DOIPubMedGoogle Scholar
  32. Statistics Canada. Life tables, Canada, provinces, and territories. 2016 [cited 2018 Mar 7].
  33. Marra  F, Marra  CA, Sadatsafavi  M, Morán-Mendoza  O, Cook  V, Elwood  RK, et al. Cost-effectiveness of a new interferon-based blood assay, QuantiFERON-TB Gold, in screening tuberculosis contacts. Int J Tuberc Lung Dis. 2008;12:141424.PubMedGoogle Scholar
  34. Menzies  D, Lewis  M, Oxlade  O. Costs for tuberculosis care in Canada. Can J Public Health. 2008;99:3916.PubMedGoogle Scholar
  35. Statistics Canada. Consumer price index, annual average, not seasonally adjusted. 2019 [cited 2018 Mar 7].
  36. Tan  MC, Marra  CA, Sadatsafavi  M, Marra  F, Morán-Mendoza  O, Moadebi  S, et al. Cost-effectiveness of LTBI treatment for TB contacts in British Columbia. Value Health. 2008;11:84252. DOIPubMedGoogle Scholar
  37. Fassbender  K, Fainsinger  RL, Carson  M, Finegan  BA. Cost trajectories at the end of life: the Canadian experience. J Pain Symptom Manage. 2009;38:7580. DOIPubMedGoogle Scholar
  38. Bauer  M, Ahmed  S, Benedetti  A, Greenaway  C, Lalli  M, Leavens  A, et al. The impact of tuberculosis on health utility: a longitudinal cohort study. Qual Life Res. 2015;24:133749. DOIPubMedGoogle Scholar
  39. Tagmouti  S, Slater  M, Benedetti  A, Kik  SV, Banaei  N, Cattamanchi  A, et al. Reproducibility of interferon gamma (IFN-γ) release Assays. A systematic review. Ann Am Thorac Soc. 2014;11:126776. DOIPubMedGoogle Scholar
  40. Pouchot  J, Grasland  A, Collet  C, Coste  J, Esdaile  JM, Vinceneux  P. Reliability of tuberculin skin test measurement. Ann Intern Med. 1997;126:2104. DOIPubMedGoogle Scholar
  41. Douglas  P, Posey  DL, Zenner  D, Robson  J, Abubakar  I, Giovinazzo  G. Capacity strengthening through pre-migration tuberculosis screening programmes: IRHWG experiences. Int J Tuberc Lung Dis. 2017;21:73745. DOIPubMedGoogle Scholar
  42. Schwartzman  K, Menzies  D. Tuberculosis screening of immigrants to low-prevalence countries. A cost-effectiveness analysis. Am J Respir Crit Care Med. 2000;161:7809. DOIPubMedGoogle Scholar
  43. Schwartzman  K, Oxlade  O, Barr  RG, Grimard  F, Acosta  I, Baez  J, et al. Domestic returns from investment in the control of tuberculosis in other countries. N Engl J Med. 2005;353:100820. DOIPubMedGoogle Scholar
  44. Sterling  TR, Villarino  ME, Borisov  AS, Shang  N, Gordin  F, Bliven-Sizemore  E, et al.; TB Trials Consortium PREVENT TB Study Team. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med. 2011;365:215566. DOIPubMedGoogle Scholar
  45. Byford  S, Raftery  J. Perspectives in economic evaluation. BMJ. 1998;316:152930. DOIPubMedGoogle Scholar
  46. Comstock  GW. Frost revisited: the modern epidemiology of tuberculosis. Am J Epidemiol. 1975;101:36382. DOIPubMedGoogle Scholar

Main Article

Page created: March 17, 2019
Page updated: March 17, 2019
Page reviewed: March 17, 2019
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.