Epidemiology and pathophysiology of diphtheria
- Luis F Barroso, MD
Luis F Barroso, MD
- Wake Forest University, Baptist Medical Center
- P Samuel Pegram, MD, FACP
P Samuel Pegram, MD, FACP
- Professor Emeritus of Medicine
- Wake Forest School of Medicine
- Section Editors
- Daniel J Sexton, MD
Daniel J Sexton, MD
- Editor-in-Chief — Infectious Diseases
- Section Editor — Bacterial Infections
- Professor of Medicine
- Duke University Medical Center
- Sheldon L Kaplan, MD
Sheldon L Kaplan, MD
- Editor-in-Chief — Pediatrics
- Section Editor — Pediatric Infectious Diseases
- Professor and Vice Chairman for Clinical Affairs
- Baylor College of Medicine
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 and pathophysiology of diphtheria will be reviewed here. The clinical manifestations, diagnosis, treatment, and prevention are discussed separately. (See "Clinical manifestations, diagnosis, and treatment of diphtheria" and "Tetanus-diphtheria toxoid vaccination in adults" and "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age" and "Diphtheria, tetanus, and pertussis immunization in infants and children 0 through 6 years of age".)
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 .
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 .To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Brooks GF, Bennett JV, Feldman RA. Diphtheria in the United States, 1959-1970. J Infect Dis 1974; 129:172.
- Bostock AD, Gilbert FR, Lewis D, Smith DC. Corynebacterium ulcerans infection associated with untreated milk. J Infect 1984; 9:286.
- Rosenau MJ. Diseases spread by milk. In: Preventive Medicine and Hygiene, 5th Ed, Appleton, New York 1928. p.718.
- Doull JA, Lara H. The epidemiologic importance of diphtheria carriers. Am J Hyg 1925; 5:508.
- 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.
- Kalapothaki V, Sapounas T, Xirouchaki E, et al. Prevalence of diphtheria carriers in a population with disappearing clinical diphtheria. Infection 1984; 12:387.
- 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.
- 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.
- 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.
- 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.
- Wilson AP. The return of Corynebacterium diphtheriae: the rise of non-toxigenic strains. J Hosp Infect 1995; 30 Suppl:306.
- Centers for Disease Control and Prevention (CDC). Diphtheria outbreak--Saraburi Province, Thailand, 1994. MMWR Morb Mortal Wkly Rep 1996; 45:271.
- 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.
- Maple PA, Efstratiou A, George RC, et al. Diphtheria immunity in UK blood donors. Lancet 1995; 345:963.
- 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.
- 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.
- Advisory Committee on Immunization Practices. Recommended adult immunization schedule: United States, 2010. Ann Intern Med 2010; 152:36.
- CDC. www.cdc.gov/nip (Accessed 3/9/05). www.cdc.gov/nip (Accessed on March 09, 2005).
- 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.
- World Health Organization. Immunization, Vaccines and Biologicals: Diptheria. http://www.who.int/immunization/monitoring_surveillance/burden/diphtheria/en/ (Accessed on February 22, 2016).
- World Health Organization. Diphtheria detected in Spain. http://www.euro.who.int/en/health-topics/disease-prevention/vaccines-and-immunization/news/news/2015/06/diphtheria-detected-in-spain (Accessed on February 22, 2016).
- European Centre for Disease Prevention and Control. Rapid Risk Assessment: A case of diptheria in Spain, 15 June 2015. http://ecdc.europa.eu/en/publications/Publications/diphtheria-spain-rapid-risk-assessment-june-2015.pdf (Accessed on February 22, 2016).
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Galazka AM, Robertson SE. Diphtheria: changing patterns in the developing world and the industrialized world. Eur J Epidemiol 1995; 11:107.
- Galazka AM, Robertson SE, Oblapenko GP. Resurgence of diphtheria. Eur J Epidemiol 1995; 11:95.
- 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.
- Bureau of Communicable Disease Control. Toxigenic diphtheria cultured from a patient with respiratory symptoms. Department of Public Health, The Commonwealth of Massachusetts, 2004.
- FREEMAN VJ. Studies on the virulence of bacteriophage-infected strains of Corynebacterium diphtheriae. J Bacteriol 1951; 61:675.
- Choe S, Bennett MJ, Fujii G, et al. The crystal structure of diphtheria toxin. Nature 1992; 357:216.
- 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.
- 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.