1887

Journal of Medical Microbiology logo

Volume 68, Issue 9

Editor's Choice Application of transdermal patches with new skin test reagents for detection of latent tuberculosis Free

Abstract

Current intradermal tuberculin skin tests for latent tuberculosis infection (LTBI) based on purified protein derivative (PPD) have poor specificity.

Developing a better skin test antigen as well as a simple skin patch test may improve and facilitate diagnostic performance.

Defined recombinant antigens that were unique to (MTB), including two potential latency-associated antigens (ESAT-6 and Rv2653c) and five DosR-encoded latency proteins (Rv1996, Rv2031c, Rv2032, DevR and Rv3716c), were used as diagnostic skin test reagents in comparison with a standard PPD. The performance of the skin tests based on the detection of delayed-type hypersensitivity (DTH) reaction in guinea pigs sensitized to MTB and bacille Calmette–Guérin (BCG) vaccine was evaluated.

The latency antigens Rv1996, Rv2031c, Rv2032 and Rv2653c and the ESAT-6 protein elicited less reactive DTH skin responses in MTB-sensitized guinea pigs than those resulting from PPD, but elicited no response in BCG-vaccinated guinea pigs. The remaining two latency antigens (DevR and Rv3716c) elicited DTH responses in both groups of animals, as did PPD. The reactivity of PPD in BCG-vaccinated guinea pigs was greater than that of any of the selected skin test reagents. Using stronger concentrations of selected skin test reagents in the patch test led to increased DTH responses that were comparable to those elicited by PPD in guinea pigs sensitized with MTB.

Transdermal application of defined purified antigens might be a promising method for LTBI screening.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): delayed-type hypersensitivity , latency-associated antigens , latent tuberculosis infection and skin patch test
© 2019 The Authors
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001037
2019-09-01
2024-04-27
Loading full text...

Full text loading...

/deliver/fulltext/jmm/68/9/1314.html?itemId=/content/journal/jmm/10.1099/jmm.0.001037&mimeType=html&fmt=ahah

References

  1. World Health Organization 2019; The End TB Strategy [Internet]. https://www.who.int/tb/strategy/en/ cited 28 May 2019
  2. Menzies RI. Tuberculin skin testing. In Reichman LB, Hershfield ES. (editors) Tuberculosis: A Comprehensive International Approach NY: Marcel Dekker; 2000 pp 279–322
     [Google Scholar]
  3. Harboe M. Antigens of PPD, old tuberculin, and autoclaved Mycobacterium bovis BCG studied by crossed immunoelectrophoresis. Am Rev Respir Dis 1981; 124:80–87 [View Article]
     [Google Scholar]
  4. van Pinxteren LAH, Ravn P, Agger EM, Pollock J, Andersen P. Diagnosis of tuberculosis based on the two specific antigens ESAT-6 and CFP10. Clinical and Vaccine Immunology 2000; 7:155–160 [View Article]
     [Google Scholar]
  5. Moradi J, Mosavari N, Ebrahimi M, Arefpajohi R, Tebianian M. Evaluation of Mycobacterium tuberculosis early secreted antigenic target 6 recombinant protein as a diagnostic marker in skin test. Osong Public Health Res Perspect 2015; 6:34–38 [View Article]
     [Google Scholar]
  6. 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; 149:177–184 [View Article]
     [Google Scholar]
  7. World Health Organization Interferon-gamma release assays IGRAs Geneva, Switzerland: WHO; 2011
     [Google Scholar]
  8. Leistikow RL, Morton RA, Bartek IL, Frimpong I, Wagner K et al. The Mycobacterium tuberculosis DosR regulon assists in metabolic homeostasis and enables rapid recovery from nonrespiring dormancy. J Bacteriol 2010; 192:1662–1670 [View Article]
     [Google Scholar]
  9. Guinn KM, Hickey MJ, Mathur SK, Zakel KL, Grotzke JE et al. Individual RD1-region genes are required for export of ESAT-6/CFP-10 and for virulence of Mycobacterium tuberculosis . Mol Microbiol 2004; 51:359–370 [View Article]
     [Google Scholar]
  10. Roupie V, Romano M, Zhang L, Korf H, Lin MY et al. Immunogenicity of eight dormancy regulon-encoded proteins of Mycobacterium tuberculosis in DNA-vaccinated and tuberculosis-infected mice. Infect Immun 2007; 75:941–949 [View Article]
     [Google Scholar]
  11. Leyten EMS, Lin MY, Franken KLMC, Friggen AH, Prins C et al. Human T-cell responses to 25 novel antigens encoded by genes of the dormancy regulon of Mycobacterium tuberculosis . Microbes Infect 2006; 8:2052–2060 [View Article]
     [Google Scholar]
  12. Geluk A, Lin MY, van Meijgaarden KE, Leyten EMS, Franken KLMC et al. T-Cell recognition of the HspX protein of Mycobacterium tuberculosis correlates with latent M. tuberculosis infection but not with M. bovis BCG vaccination. Infect Immun 2007; 75:2914–2921 [View Article]
     [Google Scholar]
  13. Saini DK, Malhotra V, Dey D, Pant N, Das TK et al. DevR-DevS is a bona fide two-component system of Mycobacterium tuberculosis that is hypoxia-responsive in the absence of the DNA-binding domain of DevR. Microbiology 2004; 150:865–875 [View Article]
     [Google Scholar]
  14. Prabhavathi M, Pathakumari B, Raja A. IFN-γ/TNF-α ratio in response to immuno proteomically identified human T-cell antigens of Mycobacterium tuberculosis - The most suitable surrogate biomarker for latent TB infection. J Infect 2015; 71:238–249 [View Article]
     [Google Scholar]
  15. Aagaard C, Brock I, Olsen A, Ottenhoff THM, Weldingh K et al. Mapping immune reactivity toward Rv2653 and Rv2654: two novel low-molecular-mass antigens found specifically in the Mycobacterium tuberculosis complex. J Infect Dis 2004; 189:812–819 [View Article]
     [Google Scholar]
  16. Sambrook J, Russell DW. Molecular Cloning: A Laboratory Manual, third edition New York: Cold Spring Harbor Laboratory Press; 2001
     [Google Scholar]
  17. Haga S, Yamaguchi R, Nagai S, Matsuo K, Yamazaki A et al. Delayed-type hypersensitivity to a recombinant mycobacterial antigen, MPB64, in guinea pigs sensitized to Mycobacterium tuberculosis or Mycobacterium bovis BCG. J Leukoc Biol 1995; 57:221–225 [View Article]
     [Google Scholar]
  18. Malaghini M, Thomaz-Soccol V, Probst CM, Krieger MA, Preti H et al. Recombinant antigen production for assays of intradermoreaction for diagnosis and surveillance of tuberculosis. J Biotechnol 2011; 156:56–58 [View Article]
     [Google Scholar]
  19. Arend SM, Franken WPJ, Aggerbeck H, Prins C, van Dissel JT 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; 88:249–261 [View Article]
     [Google Scholar]
  20. Vollmer H, Goldberger EW. A new tuberculin patch test. Arch Pediatr Adolesc Med 1937; 54:1019 and [View Article]
     [Google Scholar]
  21. Nakamura RM, Velmonte MA, Kawajiri K, Ang CF, Frias RA et al. Mpb64 mycobacterial antigen: a new skin-test reagent through patch method for rapid diagnosis of active tuberculosis. Int J Tuberc Lung Dis 1998; 2:541–546
     [Google Scholar]
  22. Nakamura RM, Einck L, Velmonte MA, Kawajiri K, Ang CF et al. Detection of active tuberculosis by an MPB-64 transdermal patch: a field study. Scand J Infect Dis 2001; 33:405–407
     [Google Scholar]
  23. Davidow A, Kanaujia GV, Shi L, Kaviar J, Guo X et al. Antibody profiles characteristic of Mycobacterium tuberculosis infection state. Infect Immun 2005; 73:6846–6851 [View Article]
     [Google Scholar]
  24. Sartain MJ, Slayden RA, Singh KK, Laal S, Belisle JT. Disease state differentiation and identification of tuberculosis biomarkers via native antigen array profiling. Mol Cell Proteomics 2006; 5:2102–2113 [View Article]
     [Google Scholar]
  25. Pai M, Minion J, Steingart K, Ramsay A. New and improved tuberculosis diagnostics: evidence, policy, practice, and impact. Curr Opin Plum Med 2010; 16:271–284
     [Google Scholar]
  26. Court D. A comparative study of the tuberculin patch test and the intracutaneous Mantoux test in children. British Med J 1939; 22:824–825
     [Google Scholar]
  27. Lin MY, Geluk A, Smith SG, Stewart AL, Friggen AH et al. Lack of immune responses to Mycobacterium tuberculosis DosR regulon proteins following Mycobacterium bovis BCG vaccination. Infect Immun 2007; 75:3523–3530 [View Article]
     [Google Scholar]
  28. Flores Valdez MA, Schoolnik GK. DosR-regulon genes induction in Mycobacterium bovis BCG under aerobic conditions. Tuberculosis 2010; 90:197–200 [View Article]
     [Google Scholar]
  29. Boon C, Dick T. Mycobacterium bovis BCG response regulator essential for hypoxic dormancy. J Bacteriol 2002; 184:6760–6767 [View Article]
     [Google Scholar]
  30. Pasche-Koo F, Hauser C. How to better understand the angry back syndrome. Dermatology 1992; 184:237–240 [View Article]
     [Google Scholar]
  31. Elhay MJ, Oettinger T, Anderson P. Delayed-type hypersensitivity responses to ESAT-6 and MPT64 from Mycobacterium tuberculosis in the guinea pig. Infect Immune 1998; 66:3454–3456
     [Google Scholar]
  32. Lyashchenko K, Manca C, Colangeli R, Heijbel A, Williams A et al. Use of Mycobacterium tuberculosis complex-specific antigen cocktails for a skin test specific for tuberculosis. Infect Immune 1998; 66:3606–3610
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001037
Loading
Application of transdermal patches with new skin test reagents for detection of latent tuberculosis
J. Med. Microbiol. 68, 1314 (2019); https://doi.org/10.1099/jmm.0.001037
/content/journal/jmm/10.1099/jmm.0.001037
/content/journal/jmm/10.1099/jmm.0.001037
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error