Skip to main content

Diagnosis and Epidemiology of Diphtheria

  • Protocol

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 15))

Abstract

Prior to the late 1980s diphtheria was regarded in many countries as one of “those rare and forgotten” diseases associated with the preimmunization era of the 1940s. Despite the success of many immunization programs, there is still much to be learned about this disease that has made a dramatic “return” in the 1990s, particularly to countries of the former Soviet Union (1) Since 1989, there has been a rapidly expanding epidemic of the disease in these countries, and thus has severe implications even for developed countries that have successfully controlled the disease for several decades (2). Diphtheria is also endemic in other countries of the world (3). The increase m international travel, migration from Eastern Europe, and also the emergence of “new strams” of the causative organism, Corynebacterlum diphtheria, causing disease have emphasized the importance of both clinical and laboratory-awareness. In addition, current immunization programs within each country should be reviewed, particularly for adults, to ensure that population immunity is adequate to prevent the re-emergence of epidemic disease in the Western world.

This is a preview of subscription content, log in via an institution.

Buying options

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Galazka, A and Robertson, S. E (1995) Resurgence of diphtheria. Eur J Epidemiol 11, 95–105

    Article  PubMed  CAS  Google Scholar 

  2. Hardy, I R B, Dittmann, S, and Sutter, R W (1996) Current situation and control strategies for resurgence of diphtheria in newly Independent states of the former Soviet Union Lancet 347, 1739–1744

    Article  PubMed  CAS  Google Scholar 

  3. Efstratiou, A and George, R C. (1996) Microbiology and epidemiology of diptheria Rev Med Microbiol 7, 31–42

    Google Scholar 

  4. MacGregor, R. R (1995) Corynebacterium diphtheriae, in Principles and Pratice of lnfictious Disease (4th ed) (Mandell, G L, Bennet, J E, and Dolin, R, eds.), Churchill Livingstone, New York, pp 1865–1872

    Google Scholar 

  5. Harnisch, J P., Tronca, E, Nolan, C M, Turck, M, and Holmes, K K (1989) Diphtheria among alcoholic urban adults. A decade of experience in Seattle Ann Intern Med 111, 71–82

    PubMed  CAS  Google Scholar 

  6. Begg, N. (1994) Manual for the management and control of diphtheria in the European Region. Copenhagen: The Expanded Programme on Immunization in the European Region of WHO. ICP/EPI038(B).

    Google Scholar 

  7. Galazka, A. and Robertson, S E (1995) Diphtheria. changing patterns in the developed world and the industrialized world Eur J Epidemiol 11, 107–117

    Article  PubMed  CAS  Google Scholar 

  8. Efstratiou, A George, R C. and Begg, N T. (1993)Non-toxigenicCorynebacterium diphtheriae in England Lancet 341, 1592,1593

    Article  Google Scholar 

  9. Pappenheimer, A. M (1984) The diphtheria bacillus and Its toxin a model system J Hyg Camb 93, 397–404

    Article  PubMed  CAS  Google Scholar 

  10. Salyers, A. A and Whitt, D D. (1994) Whitt, D D., eds.), American Society for Microbiology, Washington DC., pp 113–1

    Google Scholar 

  11. World Health Organization Regional Office for Europe Communicable Disease Report, number 13, October 1996 Diphtheria update.

    Google Scholar 

  12. De Zoysa, A, Efstratiou, A., George, R C, Vuopio-Varkila, J, Jahkola, M and Rikushin, Y. (1993) Diphtheria and travel Lancet 342, 446.

    Article  PubMed  Google Scholar 

  13. Efstratiou, A. (1995) Corynebacterium diphtheriae: molecular epidemiology and characterisation studies on epidemic and sporadic isolates Microecol Ther 25, 63–71

    Google Scholar 

  14. Colman, G, Weaver E., and Efstratiou, A (1992) Screening tests for pathogenic corynebacteria J Clin Pathol. 45, 46–48.

    Article  PubMed  CAS  Google Scholar 

  15. Efstratiou, A. and Maple, P A C. (1994) Manual for the laboratory diagnosis of diphtheria. Copenhagen: The Expanded Programme on Immunization in the European Region of WHO ICP/EP1038 (C)

    Google Scholar 

  16. Engler, K. H, Glushkevich, T., Mazurova, I. K, George, R C, and Efstratiou, A. (1997) A modified Elek test for the detection of toxigenic corynebacteria. J Clin Microbiol. 35, 495–498.

    PubMed  CAS  Google Scholar 

  17. Mikhailovich, V. M., Melmkov, M G., Mazurova, I K, Wachsmuth, I. K., Wenger, J D, Wharton, M, Nakao, H, and Popovic, T (1995) Application of PCR for detection of toxigenic Corynebacterium diphtheriae strains isolated during the Russian diphtheria epidemic, 1990 through 1994. J Clin Microbiol 33, 3061–3063

    PubMed  CAS  Google Scholar 

  18. Lucchim, G. M, Gruner, E., and Altwegg, M (1992) Rapid detection of diphtheria toxin by the polymerase chain reaction. Med Microbiol. Lett 1, 276–283.

    Google Scholar 

  19. Pallen, M. J, Hay, A. J., Puckey, L. H., and Efstratiou, A (1994) Polymerase chain reaction for screening chinical isolates of corynebacteria for the production of diphtheria toxin. J Clin. Pathol 47, 353–356.

    Article  PubMed  CAS  Google Scholar 

  20. Pallen, M J. (1991) Rapid screening for toxigenic Corynebacterium diphtheriae by the polymerase chain reaction.J Clin. Pathol 44, 1025,1026

    Article  PubMed  CAS  Google Scholar 

  21. Aravena-Roman, M, Bowman, R, and O’Neill, G. (1995) Polymerase chain reaction for the detection of toxigenic Corynebacterium diphtheriae. Pathology 27, 71–73

    CAS  Google Scholar 

  22. Hauser, D, Popoff, M R, KiredJian, M, Boquet, P., and Bimet, F. (1993) Polymerase chain reaction assay for diagnosis of potentially toxmogenic Corynebacterium diphtheriae strains: correlation with ADP-ribosylation activity assay J Clin Microbiol 31, 2720–2723.

    PubMed  CAS  Google Scholar 

  23. Groman, N., Cianciotto, N., BjOrn, M., and Rabin, M. (1983) Detection and expression of DNA homologous to the tox gene in non-toxigenic isolates of Corynebacterium diphtheriae. Infect Immun 42, 48–56

    PubMed  CAS  Google Scholar 

  24. Nakao, H., Pruckler, J M, Mazurova, I. K., Narvskala, O. V., Glushkevrch, T., MariJevski, V. F, Kravetz, A. N., Fields, B. S, Wachsmuth I K, and Popovic, T (1996) Heterogeneity of diphtheria toxin gene, [ittox, and its regulatory element, [itdtx]R, in Corynebacterium diphtheriae strains causing epidemic diphtheria in Russia and Ukraine. J.Clin Microbiol 34, 171l–1716.

    Google Scholar 

  25. Maslow, J. N., Mulligen, M. E., and Arbelt, R D. (1993) Molecular epidemiology: applications of contemporary techniques to the typing of microorganisms. Clin Infect. Dis 17, 153–164

    PubMed  CAS  Google Scholar 

  26. Anderson, J. S., Cooper, K. E., Happold, F. C., and McLeod, J W. (1933) Incidence and correlation with clinical severity of gravis, mitis and intermediate types of diphtheria bacillus in a series of 500 cases at Leeds J Pathol Bacteriol 36, 169–182

    Article  Google Scholar 

  27. Ewing, J.O. (1933) The serological grouping of the starch fermenting strains of C. diphtheriae J. Pathol. Bacteriol. 37, 345–351.

    Article  CAS  Google Scholar 

  28. Hewitt, L. F (1947) Serological typing of C diphtheriae Brit J Exp Pathol 28, 338–346

    CAS  Google Scholar 

  29. Robinson, D. T and Peeney, A A.P (1936) Serological types amongst gravis strains of C diphtheriae and their distribution. J Pathol Bacteriol. 43, 403–415.

    Article  Google Scholar 

  30. Wong, S. C and T’ung, T (1940) Further studies on type specific protein of Corynebacterium diphtheriae Proc Sot Exp Biol med 43, 749–754

    CAS  Google Scholar 

  31. Thibaut, J. and Fredericq, P (1956) Actions antibiotiques reciproques chez C diphtheriae. CR Seances Soc Biol Ses Fil 150, 1513–1514

    Google Scholar 

  32. Meitert, E and Bica-Popii, V (1972) Etude des relations antigeniques entre les phages anti-Corynebacterium hofmanm, Arch Roum. Pathol Exp Microbiol 31, 475

    PubMed  CAS  Google Scholar 

  33. Zamiri, I., McEntegart, M., and Saragea, A. (1972) Diphtheria in Iran J Hyg Camb 70, 619–625

    Article  PubMed  CAS  Google Scholar 

  34. Toshach, S, Valentine, A, and Sigurdson, S. (1977) Bacteriophage typing of Corynebacterium diphtheriae J Infect Dis. 136, 655-6

    Google Scholar 

  35. Gibson, L. F and Colman, G (1973) Diphthencin types, bacteriophage types and serotypes of Corynebacterium diphtheriae in Australia J Hyg Camb 71, 679–689

    Article  PubMed  CAS  Google Scholar 

  36. Gillies, R. R (1964) Cohcine production as an epidemiological marker of Shigella sonnet J Hyg 62, 1

    Article  CAS  Google Scholar 

  37. Saragea, A and Maximescu, P (1964) Schema provisoire de lysotypie pour Corynebacterium diphtheriae Arch Roum. Pathol Exp Microbiol 23, 817–838

    CAS  Google Scholar 

  38. Saragea, A., Maximescu, P., and Meitert, E. (1979) Corynebacterium diphtheriae Microbiological methods used in clinical and epidemiological investigations, in Methods in Microbiology, (Bergan, T. and Norris, J. R, eds ), Academic, New York,pp 61–176

    Google Scholar 

  39. Pappenheimer, A. M. and Murphy, J R. (1983) Studies on the molecular epidemiology of diphtheria Lancet 2, 923,924

    Google Scholar 

  40. Rappuoli, R, Perugmi, M., and Ratti, G (1987) DNA element of Corynebacterium diphtheriae with properties of an insertion sequence and usefulness for epidemiological studies J Bacteriol 169, 308–312

    PubMed  CAS  Google Scholar 

  41. Coyle, M B, Groman, N. B., Russell, J. Q, Harmsch, J. P, Rabin, M., and Holmes, K. K. (1989) The molecular epidemiology of three biotypes of Corynebacterium diphtheriae in the Seattle outbreak, 1972-1982. J. Infect Dis. 159, 670–679

    PubMed  CAS  Google Scholar 

  42. Greenfield, L., Bjorn, M J, Horn, G., Fond, D., Buck, G A., Collier, R J, and Kaplan, D. A (1983) Nucleotide sequence of the structural gene for diphtheria toxin carried by corynephage β. Proc Natl Acad. Set USA 80, 6853–6857.

    Article  CAS  Google Scholar 

  43. Ratti, G., Rappuoli, R, and Giannini, G (1983) The complete nucleotide sequence for the gene coding for diphtheria toxin in the corynephage ω (tox +) genome Nucleic Acids Res 11, 6589.

    Article  PubMed  CAS  Google Scholar 

  44. Rappouli, R. and Gross, R. (1990) Att sites, tox gene and insertion elements as tools for the diagnoses and molecular epidemiology of Corynebacterium diphtheriae, in Gene Probes for Bacteria (Macario, AJ.L. and Conway de Macario, E., eds), Academic, San Diego,CA, pp 205–231

    Google Scholar 

  45. Buck, G. and Groman, N B. (1981) Genetic elements novel for Corynebacterium diphtheriae. Specialised transducing elements and transposons. J. Bacteriol 148, 143–152.

    PubMed  CAS  Google Scholar 

  46. Michel, J. L., Rappuolt, R., Murphy, J. R, and Papenheimer, A M Jr. (1982) Restriction endonuclease map of the non-toxigenic corynephage (γ and its relationship to the toxrgenic corynephage PC. J Virol. 42, 510–518.

    PubMed  CAS  Google Scholar 

  47. Rappuoli, R., Perugini, M., and Falsen, E. (1988) Molecular epidemiology of the 1984-1986 outbreak of diphtheria in Sweden. N Engl J Med 318, 12–14.

    Article  PubMed  CAS  Google Scholar 

  48. Rappuoli, R., Machel, J L, and Murphy, J R. 1983. Integration of corynephages β-tox-ω-tox-and β-tox-into two attachment sites on the Coryneb acterium diphtheriae chromosome. J Bacteriol 153, 1202–1210

    Google Scholar 

  49. Cianciotto, N., Rappuoli, R, and Groman, N (1986) Detection of homology to the beta bacteriophage integration site in a wide variety of Corynebacterium spp J Bacteriol 168, 103–108

    PubMed  CAS  Google Scholar 

  50. Rappuoli, R and Ratti, G (1984) Physical map of the chromosomal region of C diphtheriae containing corynephage attachment sites att B1 and attB2 J Bacteriol 158, 325–330

    PubMed  CAS  Google Scholar 

  51. Efstratiou, A, Tiley, S M, Sangrador, A, Greenacre, E., Cookson, B D, Chen, S C A, Mallon, R, and Gilbert, G L (1993) Multiple clones of Corynebacterium diphtheriae causing invasive disease. Clin Infect Dis 17, 136.

    PubMed  CAS  Google Scholar 

  52. De Zoysa, A, Efstratiou, A, George, R C., Jahkola, M, Vuopio-Varkila, J., Deshevoi, S, Tseneva, G, and Rikushin, Y. (1995) Molecular epidemiology of Corynebacterium diphtheriae from north-western Russia and surrounding countries studied by using ribotyping and pulsed-field gel electrophoresis J Clin Microbiol 33, 1080–1083

    PubMed  CAS  Google Scholar 

  53. Popovic, T., Kombarova, S Y, Reeves, M. W., Nakao, H, Mazurova, I K, Wharton, M, Wachsmuth, I. K., and Wenger, J. D (1996) Molecular epidemiology of diphtheria in Russia, 1984-1994. J Infect Dis 174, 1064–1072.

    PubMed  CAS  Google Scholar 

  54. Arbeit, R. D., Arther, R D, Dunn, C, Kim, C, Selander, R K, and Goldstein, R (1990) Resolutton of recent evolutionary divergence among Escherichia coli from related lineages; the application of pulsed field electrophoresis to molecular epidemiology J Infect Dis 161, 230–235.

    PubMed  CAS  Google Scholar 

  55. Mulligan, M. E and Arbeit R D. (1991) Epidemiologic and clinical utility of typing systems for differentiating among strains of methicillin-resistant Staphylococcus aureus Infect Control Hosp Epidemiol 12, 20–28

    Article  CAS  Google Scholar 

  56. Strulens, M. X, Maes, N, Rost, F, Deplano, A., Jacobs, F., Liesnard, C., Bornstein, N, Grimont, F, Lauwers, S, McIntyre, M P, and Serruys, E. (1992) Genotypic and Phenotypic methods for the investigation of a nosocomial Legionella pneumophila outbreak and efficacy of control measures J Infect Dis 166, 22–30

    Google Scholar 

  57. Mokrousov, I V (1995) Arbitrary PCR typing of Corynebacterium diphtheriae strains Proceedings of the First International Meeting of the European Laboratory Working Group on Diphtheria, London, UK. PHLS Microbiol Digest 12, 89

    Google Scholar 

  58. Welsh, J and McClelland, M. (1990) Fingerprinting genomes using PCR with arbitrary primers Nucleic Acids Res 18, 7213–7218.

    Article  PubMed  CAS  Google Scholar 

  59. Williams, J G K, Kubehk, A R., Livak, K J., Rafalski, J. A, and Tingey, S V (1990) DNA polymorphisms amplified by arbitrary primers are useful as genetic markers. Nucleic Acids Res 18, 6531–6535.

    Article  PubMed  CAS  Google Scholar 

  60. Orita, M, Iwahana, H., Kanazawa, H., Hayashi, K., and Sekiya, T. (1989) Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad. Scl USA 86, 2766–2770.

    Article  CAS  Google Scholar 

  61. Reeves, M.W. and Wachsmuth, I. K. (1995) Subtyping of clinical Corynebacterium diphtheriae by multilocus enzyme electrophoresis and pulsed field gel electrophoresls Proceedings of the First International Meeting of the European Laboratory Working Group on Diphtheria, PHLS Microbiology Digest 1995, 12, 87,88

    Google Scholar 

  62. Proceedings of the First International Meeting of the European Laboratory Working Group on Diphtheria (1995), (Efstratiou, A, ed), Public Health Laboratory Service, London

    Google Scholar 

  63. Pitcher, D G, Saunders, N A, and Owen, R. J. (1989) Rapid extraction of bacterial genomic DNA with guanidium thiocyanate Lett Appl Microbiol 8, 151–156

    Article  CAS  Google Scholar 

  64. Pitcher, D G, Owen, R J, Dyal, P, and Beck, A (1987) Synthesis of a biotinylated DNA probe to detect ribosomal RNA cistrons in Providencia stuartu FEMS Microbiol Lett 48, 283–287

    Article  CAS  Google Scholar 

  65. Kaufmann, M. E. and Pitt, T. L (1994) Pulsed-field gel electrophoresls of bacterial DNA, in Methods in Practical Laboratory Bacteriology (Chart, H., ed), CRC,pp. 83–92.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Humana Press Inc.

About this protocol

Cite this protocol

Efstratiou, A., Engler, K.H., de Zoysa, A. (1998). Diagnosis and Epidemiology of Diphtheria. In: Woodford, N., Johnson, A.P. (eds) Molecular Bacteriology. Methods in Molecular Medicine™, vol 15. Humana Press. https://doi.org/10.1385/0-89603-498-4:191

Download citation

  • DOI: https://doi.org/10.1385/0-89603-498-4:191

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-498-3

  • Online ISBN: 978-1-59259-599-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics