Imported Skin Diphtheria in Four U.S. Travelers, 2015–2018

Diphtheria is a rare, vaccine-preventable bacterial disease caused by toxin-producing strains of Corynebacterium diphtheriae. It infects mainly the respiratory tract or the skin and spreads between people through respiratory droplets or contact with discharge from skin sores. Respiratory diphtheria can be life-threatening, forming an adherent pseudomembrane in the upper airway. Cutaneous (skin) diphtheria usually causes sharply outlined, slow-healing ulcers, sometimes with a membrane — and those sores can pass the bacteria to others, causing skin or respiratory disease. How severe the disease is depends on the diphtheria toxin, encoded by a toxin gene introduced by corynebacteriophages; strains that don't make toxin can also cause disease, usually milder. Vaccination may not prevent skin colonization or infection.

Four cases

From September 2015 to March 2018, CDC confirmed four cases of skin diphtheria caused by toxin-producing C. diphtheriae: two in Minnesota, one in Washington and one in New Mexico. Every patient had just returned from a country where diphtheria is endemic. No doctor suspected diphtheria; the hospitals found it by running wound isolates through MALDI-TOF mass spectrometry, a rapid screening tool for identifying bacteria. State public health laboratories confirmed the bacterium by culture, and CDC's Pertussis and Diphtheria Laboratory confirmed that all four strains (all biovar mitis) produced toxin.

• Patient 1 (September 2015) sought care for a painful abdominal wound after returning from Somalia. Four household contacts were swabbed before and at least 24 hours after preventive penicillin; all tested negative. The patient and her household were unvaccinated and declined diphtheria vaccine.
• Patient 2 (September 2017) returned from Ethiopia with an infected leg wound. He lived alone with no close contacts and reported being vaccinated when he immigrated eight years earlier. His wound had healed by the time the bacterium was identified, so no antibiotics were given.
• Patient 3 (September 2017), after a trip to the Philippines, was being evaluated for possible meningitis — unrelated to her diphtheria — when staff noticed infected insect bites on her legs. Of 16 close contacts, 11 were swabbed before preventive erythromycin and all tested negative; five had already started antibiotics. She and 12 contacts were up to date on vaccination; four unvaccinated contacts were vaccinated.
• Patient 4 (February 2018) returned from the Philippines with a draining lower-leg wound. After antibiotics his nose and throat tested negative, as did those of three household contacts swabbed before preventive penicillin. His vaccination status was unknown; none of his contacts was up to date, and all were vaccinated.

Why these cases matter

Respiratory diphtheria is nationally notifiable, but skin diphtheria was not from 1980 through 2018, so how often it occurs is unclear. In January 2019 the Council of State and Territorial Epidemiologists changed the case definition so that toxin-producing diphtheria at any site is reportable.

From 1998 to 2017, CDC's laboratory — the only U.S. laboratory that tests for diphtheria toxin — tested 248 human C. diphtheriae isolates, 130 of them from skin. Of 243 with known toxin status, five produced toxin: three of the skin cases described here and two respiratory isolates from people without matching illness. Confirmed isolates rose from an average of three a year in 1998–2011 to 33 a year in 2012–2017, and 95% of the skin isolates arrived in those later years — possibly because more labs use MALDI-TOF. Surveillance probably still undercounts skin diphtheria.

The four cases shared features that can help doctors recognize others: recent travel to countries with endemic diphtheria (several European countries have reported similar travel-related cases); no clinical suspicion, with detection only in the lab; and, in three of four, other common wound bacteria growing alongside C. diphtheriae.

What to do

• Consider skin diphtheria in travelers with infected wounds who have returned from countries where it is endemic, even when other bacteria are found too.
• Send isolates to CDC. When culture, PCR or MALDI-TOF identifies C. diphtheriae, public health laboratories should submit it for confirmation and toxin testing, and state health departments should be notified.
• If the strain produces toxin, the response mirrors that for respiratory diphtheria:
• • treat the patient with a 14-day course of erythromycin or penicillin; antitoxin is generally not recommended unless there are signs of systemic toxicity;
  • watch close contacts — household members, others in habitual close contact, and anyone exposed to the patient's secretions — for illness for 7–10 days after their last exposure;
  • swab the nose and throat of patients and contacts before antibiotics, give contacts a 7–10-day course of erythromycin or penicillin, confirm clearance by repeat swabs, and give another course if still positive;
  • bring patients and contacts up to date on diphtheria toxoid–containing vaccine.

Sources

• Griffith J, Bozio CH, Poel AJ, et al. "Imported Toxin-Producing Cutaneous Diphtheria — Minnesota, Washington, and New Mexico, 2015–2018." MMWR 68(12). CDC. Two case descriptions cut short in the imported copy were completed from the full text in PubMed Central (PMC6448983). A wound photograph provided by a patient and used with permission is not reproduced.