Infectious Agent

Toxigenic strains of Corynebacterium diphtheriae biotype mitis, gravis, intermedius , or belfanti .


Person-to-person through oral or respiratory droplets, close physical contact, and rarely, by fomites. Cutaneous diphtheria can be transmitted by contact with discharge from skin lesions.


Endemic in many countries in Asia, the South Pacific, the Middle East, Eastern Europe and in Haiti and the Dominican Republic. Since 2016, respiratory diphtheria outbreaks have occurred in Indonesia, Bangladesh, Myanmar, Vietnam, Venezuela, Haiti, South Africa, and Yemen. Cutaneous diphtheria is common in tropical countries. Respiratory and cutaneous diphtheria have been reported in travelers, though rarely. Diphtheria can affect any age group.

Clinical Presentation

The incubation period is 2–5 days (range, 1–10 days). Affected anatomic sites include the mucous membranes of the upper respiratory tract (nose, pharynx, tonsils, larynx, and trachea [respiratory diphtheria]), skin (cutaneous diphtheria), or rarely, mucous membranes at other sites (eye, ear, vulva). Nasal diphtheria can be asymptomatic or mild, with a blood-tinged discharge.

Respiratory diphtheria has a gradual onset and is characterized by a mild fever (rarely >101°F [38.3°C]), sore throat, difficulty swallowing, malaise, loss of appetite, and if the larynx is involved, hoarseness. The hallmark of respiratory diphtheria is a pseudomembrane that appears within 2–3 days of illness over the mucous lining of the tonsils, pharynx, larynx, or nares and that can extend into the trachea. The pseudomembrane is firm, fleshy, grey, and adherent; it typically will bleed after attempts to remove or dislodge it. Fatal airway obstruction can result if the pseudomembrane extends into the larynx or trachea or if a piece of it becomes dislodged. Case-fatality ratio is 5%–10%.


A presumptive diagnosis is usually based on clinical features. Diagnosis is confirmed by isolating C. diphtheriae from culture of nasal or throat swabs or membrane tissue and testing for toxin production by the Elek test. Diphtheria is a nationally notifiable disease.


Patients with respiratory diphtheria require hospitalization to monitor response to treatment and manage complications. Equine diphtheria antitoxin (DAT) is the mainstay of treatment and can be administered without waiting for laboratory confirmation. In the United States, DAT is available to physicians under an investigational new drug protocol by contacting their state health departments and then CDC at 770-488-7100.

In addition to DAT, an antibiotic (erythromycin or penicillin) should be used to eliminate the causative organisms, stop exotoxin production, and reduce communicability. Supportive care (airway, cardiac monitoring) is required. Antimicrobial prophylaxis (erythromycin or penicillin) is recommended for close contacts of patients.


All travelers should be up-to-date with diphtheria toxoid vaccine before departure. After a primary series and childhood and adolescent boosters, booster doses with a diphtheria toxoid–containing vaccine at 10-year intervals given either as Td (tetanus-diphtheria) or Tdap (tetanus-diphtheria-acellular pertussis if not previously given) should be given to all adults. This booster is particularly important for travelers who will live or work with local populations in countries where diphtheria is endemic.

CDC website: www.cdc.gov/diphtheria


  1. CDC. Fatal respiratory diphtheria in a US traveler to Haiti—Pennsylvania, 2003. MMWR Morb Mortal Wkly Rep. 2004 Jan 9;52(53):1285–6.
  2. CDC. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine in adults aged 65 years and older—Advisory Committee on Immunization Practices (ACIP), 2012. MMWR Morb Mortal Wkly Rep. 2012 June 29;61(25):468–70.  [PMID:22739778]
  3. Pan American Health Organization/World Health Organization. Epidemiological Update: Diphtheria. 15 December 2017, Washington, DC: PAHO/WHO; 2017
  4. World Health Organization. Diphtheria vaccine: WHO position paper—August 2017. Wkly Epidemiol Rec. 2017 August 4;92(31):417–36.  [PMID:28776357]
  5. World Health Organization. Review of the epidemiology of diphtheria—2000–2016. [cited 2018 Feb 20]. Available from: www.who.int/immunization/sage/meetings/2017/april/presentations_background_docs/en.


Tejpratap S. P. Tiwari, Anna Acosta