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Epidemiology, pathophysiology and clinical manifestations of diphtheria

INTRODUCTION

Diphtheria is an infectious disease caused by the gram-positive bacillus Corynebacterium diphtheriae. Infection may lead to respiratory disease, cutaneous disease or an asymptomatic carrier state. The word diphtheria comes from the Greek word for leather, which refers to the tough pharyngeal membrane that is the clinical hallmark of infection. Rarely, a similar disease can be caused by other Corynebacterium species: C. ulcerans, C. hemolyticum, and C. pseudotuberculosis.

The epidemiology, pathophysiology, and clinical manifestations of diphtheria will be reviewed here. The diagnosis, treatment, and prevention are discussed separately. (See "Diagnosis and treatment of diphtheria" and "Standard immunizations for children and adolescents", section on 'Diphtheria, tetanus, and/or pertussis vaccines' and "Tetanus-diphtheria toxoid vaccination in adults".)

EPIDEMIOLOGY

There are at least four biotypes of Corynebacterium diphtheriae: gravis, intermedius, mitis, and belfanti. All biotypes have been associated with both endemic and epidemic diphtheria, although in general, mitis strains are less toxigenic and cause less severe disease [1].

The primary modes of spread consist of close contact with infectious material from respiratory secretions (direct or via airborne droplet) or from skin lesions. Humans are believed to be the only known reservoir for C. diphtheriae, although transmission of C. ulcerans via cow’s milk has been observed [2,3]. Infection may occur throughout the year with a peak incidence in the colder months.

Asymptomatic carriers are important for transmission of diphtheria. Immunity (either via natural infection or vaccine-induced) does not prevent carriage [4,5]. In areas of endemicity, up to 5 percent of healthy individuals may have positive pharyngeal cultures [6].

         

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Literature review current through: Apr 2013. | This topic last updated: Aug 15, 2012.
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References
Top
  1. Brooks GF, Bennett JV, Feldman RA. Diphtheria in the United States, 1959-1970. J Infect Dis 1974; 129:172.
  2. Bostock AD, Gilbert FR, Lewis D, Smith DC. Corynebacterium ulcerans infection associated with untreated milk. J Infect 1984; 9:286.
  3. Rosenau MJ. Diseases spread by milk. In: Preventive Medicine and Hygiene, 5th Ed, Appleton, New York 1928. p.718.
  4. Doull JA, Lara H. The epidemiologic importance of diphtheria carriers. Am J Hyg 1925; 5:508.
  5. Miller LW, Older JJ, Drake J, Zimmerman S. Diphtheria immunization. Effect upon carriers and the control of outbreaks. Am J Dis Child 1972; 123:197.
  6. Kalapothaki V, Sapounas T, Xirouchaki E, et al. Prevalence of diphtheria carriers in a population with disappearing clinical diphtheria. Infection 1984; 12:387.
  7. English PC. Diphtheria and theories of infectious disease: centennial appreciation of the critical role of diphtheria in the history of medicine. Pediatrics 1985; 76:1.
  8. Frost WH. Infection, immunity and disease in the epidemiology of diphtheria, with special reference to some studies in Baltimore. J Prev Med 1928; 2:325.
  9. Zingher A. The Schick test performed on more than 150,000 children in public and parochial schools in New York (Manhattan and the Bronx). Am J Dis Child 1923; 25:392.
  10. Pappenheimer AM. Diphtheria: Studies on the biology of an infectious disease. In: The Harvey Lectures, Series 76, Academic Press, New York 1980-81. p.45.
  11. Wilson AP. The return of Corynebacterium diphtheriae: the rise of non-toxigenic strains. J Hosp Infect 1995; 30 Suppl:306.
  12. Centers for Disease Control and Prevention (CDC). Diphtheria outbreak--Saraburi Province, Thailand, 1994. MMWR Morb Mortal Wkly Rep 1996; 45:271.
  13. Centers for Disease Control and Prevention (CDC). Diphtheria epidemic--New Independent States of the former Soviet Union, 1990-1994. MMWR Morb Mortal Wkly Rep 1995; 44:177.
  14. Maple PA, Efstratiou A, George RC, et al. Diphtheria immunity in UK blood donors. Lancet 1995; 345:963.
  15. Weiss BP, Strassburg MA, Feeley JC. Tetanus and diphtheria immunity in an elderly population in Los Angeles County. Am J Public Health 1983; 73:802.
  16. McQuillan GM, Kruszon-Moran D, Deforest A, et al. Serologic immunity to diphtheria and tetanus in the United States. Ann Intern Med 2002; 136:660.
  17. Advisory Committee on Immunization Practices. Recommended adult immunization schedule: United States, 2010. Ann Intern Med 2010; 152:36.
  18. CDC. www.cdc.gov/nip (Accessed 3/9/05). www.cdc.gov/nip (Accessed on March 09, 2005).
  19. Coyle MB, Groman NB, Russell JQ, et al. The molecular epidemiology of three biotypes of Corynebacterium diphtheriae in the Seattle outbreak, 1972-1982. J Infect Dis 1989; 159:670.
  20. Centers for Disease Control and Prevention (CDC). Notes from the field: respiratory diphtheria-like illness caused by toxigenic Corynebacterium ulcerans --- Idaho, 2010. MMWR Morb Mortal Wkly Rep 2011; 60:77.
  21. Tiwari TS, Golaz A, Yu DT, et al. Investigations of 2 cases of diphtheria-like illness due to toxigenic Corynebacterium ulcerans. Clin Infect Dis 2008; 46:395.
  22. Taylor J, Saveedra-Campos M, Harwood D, et al. Toxigenic Corynebacterium ulcerans infection in a veterinary student in London, United Kingdom, May 2010. Euro Surveill 2010; 15.
  23. Wagner KS, White JM, Crowcroft NS, et al. Diphtheria in the United Kingdom, 1986-2008: the increasing role of Corynebacterium ulcerans. Epidemiol Infect 2010; 138:1519.
  24. Nakao H, Pruckler JM, Mazurova IK, et al. Heterogeneity of diphtheria toxin gene, tox, and its regulatory element, dtxR, in Corynebacterium diphtheriae strains causing epidemic diphtheria in Russia and Ukraine. J Clin Microbiol 1996; 34:1711.
  25. Hardy IR, Dittmann S, Sutter RW. Current situation and control strategies for resurgence of diphtheria in newly independent states of the former Soviet Union. Lancet 1996; 347:1739.
  26. Dittmann S, Wharton M, Vitek C, et al. Successful control of epidemic diphtheria in the states of the Former Union of Soviet Socialist Republics: lessons learned. J Infect Dis 2000; 181 Suppl 1:S10.
  27. Galazka AM, Robertson SE. Diphtheria: changing patterns in the developing world and the industrialized world. Eur J Epidemiol 1995; 11:107.
  28. Galazka AM, Robertson SE, Oblapenko GP. Resurgence of diphtheria. Eur J Epidemiol 1995; 11:95.
  29. Centers for Disease Control and Prevention (CDC). Fatal respiratory diphtheria in a U.S. traveler to Haiti--Pennsylvania, 2003. MMWR Morb Mortal Wkly Rep 2004; 52:1285.
  30. Bureau of Communicable Disease Control. Toxigenic diphtheria cultured from a patient with respiratory symptoms. Department of Public Health, The Commonwealth of Massachusetts, 2004.
  31. FREEMAN VJ. Studies on the virulence of bacteriophage-infected strains of Corynebacterium diphtheriae. J Bacteriol 1951; 61:675.
  32. Choe S, Bennett MJ, Fujii G, et al. The crystal structure of diphtheria toxin. Nature 1992; 357:216.
  33. Naglich JG, Rolf JM, Eidels L. Expression of functional diphtheria toxin receptors on highly toxin-sensitive mouse cells that specifically bind radioiodinated toxin. Proc Natl Acad Sci U S A 1992; 89:2170.
  34. Naglich JG, Metherall JE, Russell DW, Eidels L. Expression cloning of a diphtheria toxin receptor: identity with a heparin-binding EGF-like growth factor precursor. Cell 1992; 69:1051.
  35. Wong TP, Groman N. Production of diphtheria toxin by selected isolates of Corynebacterium ulcerans and Corynebacterium pseudotuberculosis. Infect Immun 1984; 43:1114.
  36. NAIDITCH MJ, BOWER AG. Diphtheria; a study of 1,433 cases observed during a ten-year period at the Los Angeles County Hospital. Am J Med 1954; 17:229.
  37. Kadirova R, Kartoglu HU, Strebel PM. Clinical characteristics and management of 676 hospitalized diphtheria cases, Kyrgyz Republic, 1995. J Infect Dis 2000; 181 Suppl 1:S110.
  38. Lumio JT, Groundstroem KW, Melnick OB, et al. Electrocardiographic abnormalities in patients with diphtheria: a prospective study. Am J Med 2004; 116:78.
  39. BOYER NH, WEINSTEIN L. Diphtheritic myocarditis. N Engl J Med 1948; 239:913.
  40. MORGAN BC. CARDIAC COMPLICATIONS OF DIPHTHERIA. Pediatrics 1963; 32:549.
  41. Kneen R, Nguyen MD, Solomon T, et al. Clinical features and predictors of diphtheritic cardiomyopathy in Vietnamese children. Clin Infect Dis 2004; 39:1591.
  42. Jayashree M, Shruthi N, Singhi S. Predictors of outcome in patients with diphtheria receiving intensive care. Indian Pediatr 2006; 43:155.
  43. Dobie RA, Tobey DN. Clinical features of diphtheria in the respiratory tract. JAMA 1979; 242:2197.
  44. Wilson AP, Efstratiou A, Weaver E, et al. Unusual non-toxigenic Corynebacterium diphtheriae in homosexual men. Lancet 1992; 339:998.
  45. Tiley SM, Kociuba KR, Heron LG, Munro R. Infective endocarditis due to nontoxigenic Corynebacterium diphtheriae: report of seven cases and review. Clin Infect Dis 1993; 16:271.
  46. Gruner E, Opravil M, Altwegg M, von Graevenitz A. Nontoxigenic Corynebacterium diphtheriae isolated from intravenous drug users. Clin Infect Dis 1994; 18:94.
  47. Höfler W. Cutaneous diphtheria. Int J Dermatol 1991; 30:845.
  48. Lowe CF, Bernard KA, Romney MG. Cutaneous diphtheria in the urban poor population of Vancouver, British Columbia, Canada: a 10-year review. J Clin Microbiol 2011; 49:2664.
  49. Bray JP, Burt EG, Potter EV, et al. Epidemic diphtheria and skin infections in Trinidad. J Infect Dis 1972; 126:34.
  50. Sing A, Heesemann J. Imported cutaneous diphtheria, Germany, 1997-2003. Emerg Infect Dis 2005; 11:343.
  51. Zeegelaar JE, Faber WR. Imported tropical infectious ulcers in travelers. Am J Clin Dermatol 2008; 9:219.
  52. de Benoist AC, White JM, Efstratiou A, et al. Imported cutaneous diphtheria, United Kingdom. Emerg Infect Dis 2004; 10:511.
  53. Harnisch JP, Tronca E, Nolan CM, et al. Diphtheria among alcoholic urban adults. A decade of experience in Seattle. Ann Intern Med 1989; 111:71.
  54. Belsey MA, Sinclair M, Roder MR, LeBlanc DR. Corynebacterium diphtheriae skin infections in Alabama and Louisiana. A factor in the epidemiology of diphtheria. N Engl J Med 1969; 280:135.