Vaccine Preventable Diseases in Australia, 2005 to 2007

3.1 Diphtheria

Page last updated: 24 December 2010

Diphtheria is an acute toxin-mediated systemic disease caused by the bacterium Corynebacterium diphtheriae. Infection remains localised to the throat or skin and disease is mainly due to local inflammation with membrane formation and/or systemic toxaemia. Pharyngeal diphtheria presents with a membranous inflammation of the upper respiratory tract, which may be extensive enough to cause airway obstruction. Damage to other organs including the myocardium, nervous system and kidneys, caused by the organism’s exotoxin, may complicate pharyngeal or cutaneous diphtheria.1,2 Non-toxigenic C.ádiphtheriae usually causes mild throat or skin infection, which is occasionally complicated by invasive disease including endocarditis or septic arthritis. Corynebacterium ulcerans, a bacterium found in cattle and cats, can also express diphtheria toxin and cause a zoonotic infection in humans that is similar to diphtheria.3–6

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Case definitions

Notifications

See Appendix 6.6 for pre-2004 definition

National definition from January 2004:7

Both confirmed and probable cases are notifiable.

Isolation of toxigenic Corynebacterium diphtheriae or toxigenic C.áulcerans (confirmed case).

OR

Isolation of C.ádiphtheriae or C.áulcerans (toxin production unknown) and one of the following presentations as clinical evidence:

pharyngitis and/or laryngitis (with or without membrane) (probable case); or toxic (cardiac or neurological) symptoms (probable case).

OR

Clinical evidence as above and an epidemiological link to a confirmed case (probable case).

Hospitalisations and deaths

The ICD-10-AM/ICD-10 code A36 (diphtheria) was used to identify hospitalisations and deaths.

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Notifications, hospitalisations and deaths

There were no notifications of diphtheria in 2006 or 2007. For the 2-year period 2005/2006 to 2006/2007, there were 49 hospitalisations coded as diphtheria. Most were cutaneous (A36.3; n=31), or classified non-specifically as other (A36.8; n=9) or unspecified (A36.9; n=8) diphtheria. Slightly more males than females were hospitalised with diphtheria (male:female ratio 1.5:1). The highest average annual rate of hospitalisation coded as diphtheria occurred in the Northern Territory (6.2 per 100,000) although diphtheria was not the principal diagnosis of any of these hospitalisation episodes. There was 1 death coded as due to diphtheria (unspecified) in a young adult male (age group 30–35 years) in 2006. However, there were no notifications or hospitalisations coded as due to diphtheria in the relevant jurisdiction in 2006.

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Comment

Diphtheria has become rare in Australia. A cutaneous toxigenic case acquired in East Timor and notified in 2001 was the first case notified since 1993. Culture positive cutaneous and throat infections with non-toxigenic C.ádiphtheriae are endemic in the Northern Territory,8 but these are not classified as diphtheria in the absence of relevant symptoms. In the absence of any notifications during the period 2006–2007, the 49 hospitalisations, with only one having diphtheria as the principal diagnosis, were presumably non-toxigenic or culture negative suspected diphtheria cases or coding errors. It is very likely that the higher rate of hospitalisations coded as diphtheria in the Northern Territory reflects the detection of non-toxigenic types endemic in the region. The death coded as due to diphtheria in 2006 is likely to be a coding error as the relevant jurisdiction has confirmed that there were no notified cases in 2006.

Diphtheria is still a global problem with 15 countries in Asia, Africa, the Middle East, the Caribbean and Europe reporting 10 or more cases of diphtheria to the World Health Organization in 2007;9 a total of 4,190ácases were reported globally in 2007. Notably, more than 3,000 cases were reported in 2007 from India,9 where diphtheria remains endemic.10 Five recent studies of diphtheria cases in different regions of India have each documented lack of immunisation as a major risk factor.10–14 The large outbreak of diphtheria in the newly independent states of the former Soviet Union in the 1990s15 underscored the risk of diphtheria returning when high vaccination coverage in children (who are critical vectors of respiratory transmission) is not maintained. A specific diphtheria surveillance network has recently been established in Europe.16

In countries with high childhood vaccination coverage against diphtheria, such as Australia, the United Kingdom (UK), Germany, the United States of America (USA) and Canada, cutaneous lesions are the most common manifestation of C.ádiphtheriae infection. Cutaneous infection may be caused by local circulating non-toxigenic strains17 (which can also cause invasive disease, including bacteraemia, endocarditis and septic arthritis, particularly in persons with risk factors such as homelessness, alcoholism or diabetes)18 or by imported toxigenic types due to overseas travel.19,20 Cutaneous C.ádiphtheriae infection (due to toxigenic or non-toxigenic strains) may be difficult to diagnose due to a low index of suspicion,21,22 may cause chronic infection, and may serve as a reservoir for ongoing transmission with greater efficiency than respiratory infection.17,19 The frequency of international travel now means that, even in countries such as Australia where diphtheria is rare, exposure to a toxigenic strain may occur, with potentially fatal consequences in unvaccinated individuals or in those whose vaccine induced immunity has waned.23,24 Australian serosurveillance data indicate that, while childhood protection is excellent (>99%), waning immunity in adults has resulted in a potentially susceptible population with travel the most likely source of exposure.25 Australians travelling to countries where diphtheria remains a problem, including countries in the Asia–Pacific region such as India, Pakistan, Indonesia, the Philippines, Nepal, Bangladesh and Vietnam,9 should ensure that they are protected against diphtheria through booster immunisation.26

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References

1. Vitek CR, Wharton M. Diphtheria toxoid. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 5th edn. Philadelphia, PA: Saunders Elsevier, 2008.

2. Diphtheria. In: Heymann DL, ed. Control of Communicable Diseases Manual. 19th edn. Washington, DC: American Public Health Association, 2008.

3. Hatanaka A, Tsunoda A, Okamoto M, Ooe K, Nakamura A, Miyakoshi M, et al. Corynebacterium ulcerans diphtheria in Japan [letter]. Emerg Infect Dis 2003;9(6):752–753.

4. DeWinter LM, Bernard KA, Romney MG. Human clinical isolates of Corynebacterium diphtheriae and Corynebacterium ulcerans collected in Canada from 1999 to 2003 but not fitting reporting criteria for cases of diphtheria. J Clin Microbiol 2005;43(7):3447–3449.

5. Tiwari TS, Golaz A, Yu DT, Ehresmann KR, Jones TF, Hill HE, et al. Investigations of 2 cases of diphtheria-like illness due to toxigenic Corynebacterium ulcerans. Clin Infect Dis 2008;46(3):395–401.

6. Elden S, Coole L, Efstratiou A, Doshi N. Laboratory-confirmed case of toxigenic Corynebacterium ulcerans. Euro Surveill 2007;12(13):p11=3166. Available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=3166 Accessed on 9 January 2009.

7. Communicable Diseases Network Australia. Surveillance case definitions for the Australian National Notifiable Diseases Surveillance System. 2004. Available from: http://www.health.gov.au/internet/main/publishing.nsf/Content/cdna-casedefinitions.htm Accessed on 24 August 2009.

8. Centre for Disease Control Northern Territory. Guidelines for the control of diphtheria in the Northern Territory. Darwin: Northern Territory Government Department of Health and Community Services, 2004. Available from: http://www.health.nt.gov.au/library/scripts/objectifyMedia.aspx?file=pdf/10/85.pdf&siteID=1&str_title=Diphtheria.pdf Accessed on 17 February 2009.

9. World Health Organization. Data, statistics and graphics by subject. Disease incidence. Geneva; World Health Organization, 2008. Available from: http://www.who.int/immunization_monitoring/data/data_subject/en/index.html Accessed on 9áJanuary 2009.

10. Khan N, Shastri J, Aigal U, Doctor B. Resurgence of diphtheria in the vaccination era. Indian J Med Microbiol 2007;25(4):434.

11. Bitragunta S, Murhekar MV, Hutin YJ, Penumur PP, Gupte MD. Persistence of diphtheria, Hyderabad, India, 2003–2006. Emerg Infect Dis 2008;14(7):1144–1146.

12. Jayashree M, Shruthi N, Singhi S. Predictors of outcome in patients with diphtheria receiving intensive care. Indian Pediatr 2006;43(2):155–160.

13. Sharma NC, Banavaliker JN, Ranjan R, Kumar R. Bacteriological and epidemiological characteristics of diphtheria cases in and around Delhi—a retrospective study. Indian J Med Res 2007;126(6):545–552.

14. Dravid MN, Joshi SA. Resurgence of diphtheria in Malegaon and Dhule regions of north Maharashtra. Indian J Med Res 2008;127(6):616–617.

15. Vitek CR, Wharton M. Diphtheria in the former Soviet Union: reemergence of a pandemic disease. Emerg Infect Dis 1998;4(4):539–550.

16. Neal S, Efstratiou A. DIPNET – establishment of a dedicated surveillance network for diphtheria in Europe. Euro Surveill 2007;12(12):p11=754. Available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=754 Accessed on 9 January 2009.

17. Wren MW, Shetty N. Infections with Corynebacterium diphtheriae: six years’ experience at an inner London teaching hospital. Br J Biomed Sci 2005;62(1):1–4.

18. Romney MG, Roscoe DL, Bernard K, Lai S, Efstratiou A, Clarke AM. Emergence of an invasive clone of nontoxigenic Corynebacterium diphtheriae in the urban poor population of Vancouver, Canada. J Clin Microbiol 2006;44(5):1625–1629.

19. de Benoist AC, White JM, Efstratiou A, Kelly C, Mann G, Nazareth B, et al. Imported cutaneous diphtheria, United Kingdom. Emerg Infect Dis 2004;10(3):511–513.

20. Sing A, Heesemann J. Imported cutaneous diphtheria, Germany, 1997–2003. Emerg Infect Dis 2005;11(2):343–344.

21. Vetrichevvel TP, Pise GA, Agrawal KK, Thappa DM. Cutaneous diphtheria masquerading as a sexually transmitted disease. Indian J Dermatol Venereol Leprol 2008;74(2):187.

22. Lee PL, Lemos B, O’Brien SH, English JC 3rd, Zirwas MJ. Cutaneous diphtheroid infection and review of other cutaneous Gram-positive Bacillus infections. Cutis 2007;79(5):371–377.

23. Lumio J, Suomalainen P, Ílander RM, SaxÚn H, Salo E. Fatal case of diphtheria in an unvaccinated infant in Finland. Pediatr Infect Dis J 2003;22(9):844–846.

24. Centers for Disease Control and Prevention. Fatal respiratory diphtheria in a U.S. traveler to Haiti—Pennsylvania, 2003. MMWR Morb Mortal Wkly Rep 2004;52(53):1285–1286.

25. Gidding HF, Backhouse JL, Burgess MA, Gilbert GL. Immunity to diphtheria and tetanus in Australia: a national serosurvey. Med J Aust 2005;183(6):301–304.

26. Cameron C, White J, Power D, Crowcroft N. Diphtheria boosters for adults: balancing risks. Travel Med Infect Dis 2007;5(1):35–39.

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