Author(s): Anna Acosta, Sarah Bennett

Infectious Agent

Diphtheria is caused by toxigenic strains of Corynebacterium diphtheriae biotype mitis, gravis, intermedius, or belfanti. Toxigenic strains of C. ulcerans also cause rare cases of a diphtheria-like illness.

Transmission

Transmission occurs person-to-person through respiratory droplets or direct contact with secretions from cutaneous diphtheria lesions, and rarely, by fomites.

Epidemiology

Diphtheria is endemic to many regions around the world: Haiti and the Dominican Republic in the Americas; Asia and the South Pacific; Eastern Europe; and the Middle East. Since 2016, respiratory diphtheria outbreaks have occurred in Bangladesh, Burma (Myanmar), Haiti, Indonesia, South Africa, Ukraine, Venezuela, Vietnam, and Yemen. Cutaneous diphtheria is common in tropical countries. Respiratory and cutaneous diphtheria have been reported in travelers to countries with endemic disease. The last case of respiratory diphtheria in a US traveler was reported in 2003, but toxin-producing cutaneous C. diphtheriae was identified from 4 US residents who returned from travel between September 2015 and March 2018. Diphtheria can affect any age group, especially people who are not fully vaccinated with diphtheria toxoid vaccine.

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 and 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 onset, covers 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. The case-fatality ratio is 5%–10%.

Diagnosis

A presumptive diagnosis is usually based on clinical features. Diagnosis is confirmed by isolating C. diphtheriae from culture of nasal or throat swabs or pseudomembrane tissue and testing for toxin production by the Elek test. Laboratory capacity for diphtheria culture and Elek testing varies by country, and testing might be available through national reference or commercial laboratories. In the United States, the Centers for Disease Control and Prevention (CDC) has the only laboratory able to perform Elek testing. Diphtheria is a nationally notifiable disease in the United States, and clinicians can contact their state health department or the CDC Emergency Operations Center for more information.

Treatment

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 department, followed by the CDC Emergency Operations Center at 770-488-7100.

In addition to DAT, treating physicians should prescribe an antibiotic (erythromycin or penicillin) to eliminate the causative organisms, stop toxin production, and reduce communicability. Patients will require supportive care, including airway and cardiac monitoring. In addition, close contacts of patients should receive antimicrobial prophylaxis with erythromycin or penicillin.

Prevention

All travelers should be up to date with diphtheria toxoid vaccine before departure. After a primary series and childhood and adolescent boosters, all adults should receive booster doses with a diphtheria toxoid–containing vaccine at 10-year intervals, given either as Td (tetanus-diphtheria) or Tdap (tetanus-diphtheria-acellular pertussis). This booster is particularly important for travelers who will live or work in countries where diphtheria is endemic.

CDC website: Diphtheria