In 2022, Western Europe experienced the largest surge in reported diphtheria infections in 70 years. Clinical and genomic data from the outbreak point toward transmission routes along established migration pathways into Europe. Rapid interventions successfully contained the outbreak, yet strains from that period continue to cause new infections in the region.

Throughout 2022, several European countries reported an unusually high number of infections caused by Corynebacterium diphtheriae, primarily affecting recently arrived refugees. At the time, transmission within local populations of affected countries was not documented.

A new study in the prestigious New England Journal of Medicine (NEJM) now reveals, for the first time, the transmission pathways involved. A European research consortium analyzed genomic profiles from 363 bacterial isolates. These samples originated from patients in 10 countries that reported a rise in diphtheria cases between January and the end of November 2022, and who jointly analyzed their sequencing data: Germany (118 isolates), Austria (66), the United Kingdom (59), Switzerland (52), France (30), Belgium (21), Norway (8), the Netherlands (5), Italy (3) and Spain (1).

Diphtheria transmission along migrant travel routes
“The diphtheria strains reported in 2022 share a high degree of genetic similarity, indicating either a common source of infection or specific locations along migration routes to Europe where sustained transmission occurred,” says Andreas Hoefer, microbiology expert at the European Centre for Disease Prevention and Control (ECDC) and co-first author of the study.

According to the study, nearly all of the 362 patients (98%) were male, with an average age of 18 at the time of data collection. The majority (96%) had recently traveled from their countries of origin to the countries where diphtheria was subsequently diagnosed. Of the 266 patients for whom country-of-origin data were available, 222 (83%) originated from Afghanistan or Syria. Most followed migration routes through Western Balkan countries to their destinations, with a total of 28 transit countries documented.

Of the 346 patients with clinical data, 268 (77%) had cutaneous diphtheria, which affects the skin, while 52 (15%) had a respiratory form that attacks the airways. “Diphtheria presents with a broad spectrum of clinical symptoms. Particularly feared are respiratory complications caused by toxin-producing bacteria, which can be life-threatening,” explains Adrian Egli, director of the Institute of Medical Microbiology at the University of Zurich and one of the study leaders.

Rapid exchange of sequencing data enabled swift response across Europe
“Rapid sharing of genomic sequencing data among reporting countries allowed to define the commonalities of the diphtheria strains across borders,” adds Sylvain Brisse, a professor at the Institut Pasteur and another leading author of the study.

“The detection of Austria’s first respiratory diphtheria case in nearly 30 years, in 2022, highlights the critical importance of cross-border information sharing and international collaboration in outbreak response,” says Stefanie Schindler, microbiologist at the Austrian Agency for Health and Food Safety (AGES) and co-author of the study. “We noticed a dramatic increase of toxin-producing diphtheria bacteria in Germany in the summer of 2022, and initially informed our Austrian and Swiss colleagues in the informal European diphtheria network,” says Andreas Sing, head of Germany’s National Reference Laboratory for Diphtheria at the Bavarian Health and Food Safety Authority (LGL).

The sequencing analysis also provided insights into the antibiotic susceptibility of bacterial strains, subsequently confirmed by antimicrobial susceptibility testing. This information was instrumental in guiding public health measures, including identifying and screening for resistance to antibiotics such as erythromycin.

Update vaccinations and remain vigilant
The vaccination status of affected patients was challenging to assess due to incomplete medical documentation. According to available data, only four patients were vaccinated against diphtheria, 10 reported being unvaccinated, and the vaccination status of 290 patients remained unknown. For those who have completed their diphtheria vaccination series, the likelihood of contracting the disease is very low. Typically, a booster vaccination 10 years after the last dose is sufficient for maintaining protection.

Silvia Funke, ECDC expert on vaccine-preventable diseases concludes that “the study shows how important it is to ensure that everyone’s vaccination status against diphtheria is up to date, including among vulnerable people such as migrants, people experiencing homelessness, people who inject drugs or unvaccinated persons. This also means that clinicians need to be vigilant of and pay attention to diphtheria symptoms, especially when their patients are in vulnerable groups or have any link to these populations”.

By the end of 2022, rapid interventions such as contact tracing and screening for secondary cases significantly curtailed the outbreak. However, genomic data show that certain strains continue to circulate, prompting continued vigilance by public health authorities and healthcare providers. “To date, neither the full extent of circulation, nor the exact place of infection has been determined. Which is why both public health professionals and healthcare providers need to remain vigilant to avoid further spread of diphtheria in Europe,” Hoefer emphasizes.

Diphtheria: disease and vaccination
Diphtheria is a notifiable, vaccine-preventable infectious disease caused by toxin-producing bacteria, primarily Corynebacterium diphtheriae and Corynebacterium ulcerans. Transmission occurs via respiratory droplets from infected individuals (e.g., through coughing or sneezing). Cutaneous diphtheria can be transmitted through direct contact with wounds or lesions of infected persons. Humans are the only significant reservoir for C. diphtheriae. Individuals infected with diphtheria bacteria, both symptomatic or asymptomatic, can transmit the bacteria to others.

Due to mass immunization with effective vaccines, diphtheria is now rare in Europe, with global cases significantly reduced in recent decades. Diphtheria vaccination is part of national routine immunization programs throughout Europe, often combined with other vaccines.

Further information: ECDC Diphtheria Facts, EU Vaccine Information