No 34 - 2026

First case of diphtheria in Denmark since 2020

In week 32, Statens Serum Institut (SSI) detected the first case of cutaneous diphtheria in Denmark since 2020. The case was caused by Corynebacterium ulcerans. An elderly person was seen at an orthopedic outpatient clinic at the end of July with a chronic, non-healing wound on the foot. A swab from the area was sent in for culture at the local Department of Clinical Microbiology (DCM), and the patient was treated with empirical antibiotics. The patient was otherwise well and was not admitted to hospital.

The swab showed growth of both Pseudomonas aeruginosa and C. ulcerans, and the C. ulcerans isolate was sent to SSI for toxin testing. Genotypic testing for the toxin gene by PCR analysis was inconclusive on August 4th, but toxin production was confirmed by Elek-test on August 7th. At this time, the patient was still well and receiving appropriate antibiotics covering the resistance pattern of this isolate, initially amoxicillin and dicloxacillin; these were later replaced with dicloxacillin with ciprofloxacin because of growth of P. aeruginosa, while amoxicillin was continued. There was no indication for treatment with diphtheria antitoxin. There was no known exposure to animals, and the patient had not consumed unpasteurized dairy products.

The Danish Patient Safety Authority (STPS) was immediately informed of the result and assessed the need for screening of close contacts and possible post-exposure prophylaxis.

C. ulcerans is a zoonotic infection, and because of the location of the wound, and because the likelihood of human-to-human transmission was assessed as low, STPS chose in this case not to carry out further contact tracing. The patient was last vaccinated against diphtheria in 2018 and received a booster dose of dT-vaccine after confirmation of cutaneous diphtheria. The patient has been referred for further follow-up by the infectious diseases service.

Diphtheria is caused by the effects of diphtheria toxin on the body

Diphtheria is a disease caused by tox-gene-carrying strains of C. diphtheriae, C. ulcerans or, very rarely, C. pseudotuberculosis. Diphtheria bacteria may contain a phage-carried gene – the tox gene – and the majority of isolates carrying this tox gene produce diphtheria toxin, which can affect the heart muscle, kidneys and nervous system, and the disease can be fatal. All isolates of C. diphtheriae, C. ulcerans and C. pseudotuberculosis must be sent to SSI for toxin testing (Executive Order No. 452 of 08/05/2026). Other corynebacteria that have also been shown to be capable of carrying the tox gene include C. belfanti, C. rouxii, C. ramonii and C. silvaticum, and isolates containing these bacteria may also be submitted to SSI for toxin testing. Toxin testing consists of a genotypic toxin determination (PCR for the tox gene) followed by a phenotypic toxin determination (a modified Elek-test) in cases where the tox gene was detected.

The disease presents as an acute infection of the upper respiratory tract (pharyngeal or respiratory diphtheria) or of the skin (cutaneous diphtheria). In classical pharyngeal diphtheria, there is sudden-onset pharyngitis with painful swallowing and fever, and thick white-greyish coatings may form on the tonsils, soft palate and back of the pharynx. The coatings are often called pseudomembranes (a false membrane) and are caused by necrotic tissue. Swollen and tender glands in the neck may be seen, possibly so severe that the patient becomes hoarse and develops difficulty breathing. Cutaneous diphtheria may be associated with chronic wounds, and in some cases, this wound may also be covered by a pseudomembrane. Diphtheria antitoxin (DAT) neutralises free diphtheria toxin from C. diphtheriae and C. ulcerans. Respiratory diphtheria is always treated with DAT, and it significantly reduces mortality. It is normally recommended to treat cutaneous diphtheria with DAT if a wound is larger than 2 cm² and membranous.

The likelihood of a toxin-producing diphtheria strain depends on the bacterial species

C. ulcerans was first described as a cause of diphtheria in the 1920s. It can cause udder infection in cows, and humans can rarely become infected by drinking raw (unpasteurized) milk. Today, infections in humans are most often associated with contact with pets. Human-to-human spread is extremely rare but has been described. Toxin-producing C. ulcerans tends to cause milder infection compared with toxin-producing C. diphtheriae, but infections can be severe and, in rare cases, fatal. A report from the British authority, the UK Health Security Agency, showed that 64.6% of C. ulcerans isolates submitted for testing between 2014 and 2021 produced diphtheria toxin, compared with 4.9% of C. diphtheriae isolates.

Comment

Diphtheria remains a very rare disease in Denmark, and the reference laboratory at SSI performs toxin testing on approximately 8–12 isolates per year. The two most recent cases of diphtheria in Denmark were caused by C. ulcerans: one case of cutaneous diphtheria in 2020 and one case of pharyngeal diphtheria in 2017, EPI-NEWS 46/2017. The most recent case of cutaneous diphtheria caused by C. diphtheriae was in 2015, EPI-NEWS 27-33/2015, and it has been almost 30 years since classical pharyngeal diphtheria was last detected in Denmark, EPI-NEWS 1/1999. Although diphtheria is a rare disease in Denmark, clinicians should be aware that other European countries have seen cases of diphtheria caused by C. diphtheriae in recent years, EPI-NEWS 21/2025, particularly among asylum seekers, homeless people and people who use drugs, but there have also been cases among people outside these groups, and diphtheria should be included in the differential diagnosis in patients with relevant symptoms.

(A. Ronayne, Bacteria, Parasites and Fungi, D. Bomark, Department of Joint and Bone Surgery, SUH, Nykøbing F, D. Back Holmgaard, DCM SUH, Slagelse, P.H. Andersen, Department of Infectious Disease Epidemiology and Prevention)