Health authorities across Europe are sounding the alarm over an unexpected resurgence of diphtheria — including a sharp increase in cutaneous infections — after decades of near elimination. The rise in cases has prompted renewed calls for adult vaccination and greater clinical vigilance among healthcare providers.

Diphtheria is an acute bacterial infection most often caused by Corynebacterium diphtheriae. Its severity stems from a potent toxin capable of damaging the heart, kidneys, and nervous system. The classic form, respiratory diphtheria, typically presents as febrile pharyngitis with pseudomembranes, while the cutaneous form produces greyish-white membranes on preexisting wounds or ulcers. Corynebacterium ulcerans can cause similar symptoms, whereas Corynebacterium pseudotuberculosis most commonly presents with lymphadenitis.

Highly contagious, diphtheria spreads mainly through respiratory droplets or direct contact with infected skin lesions and less often through contaminated objects. Infections caused by C ulcerans are generally linked to domestic animals — particularly dogs and cats — and do not spread between humans. By contrast, C pseudotuberculosis infections are typically associated with contact with small ruminants, such as goats.

The incubation period is 2-5 days, and the case fatality rate for respiratory diphtheria remains 5%-10%. Diagnosis relies on clinical evaluation, bacterial culture of pharyngeal samples, and confirmation via toxin testing at the National Reference Center at Institut Pasteur in Paris, France.

Effective Vaccination, but Waning Adult Immunity

Since mandatory vaccination was introduced globally in the 1950s, the incidence of diphtheria has dropped dramatically, making it a rare disease in most parts of the world.

In France, diphtheria vaccination is part of the national immunisation schedule, which includes:

• Primary vaccination at 2 months
• Booster at 11 months
• Further boosters at 6 years, 11-13 years, and again in adulthood at 25, 45, and 65 years, followed by decennial boosters thereafter

As a notifiable disease, diphtheria vaccination is mandatory for healthcare workers and recommended for travellers to endemic regions.

However, vaccine coverage among adults remains inadequate — only about 50% of people aged 65 years are protected, far below the herd immunity threshold of 80%-85% needed to prevent transmission.

A Rare Outbreak Affecting Europe’s Most Vulnerable

In 2022, Europe experienced its largest diphtheria outbreak in seven decades, beginning primarily among migrant populations and later spreading to other vulnerable groups, including people who are homeless, inject drugs, or are unvaccinated or elderly.

Across Europe, 320 cases were reported in 2022, followed by 165 in 2023 and 56 in 2024. In France alone, 60 cases were recorded in 2022, 39 in 2023 (31 cutaneous), and 21 in 2024 (18 cutaneous).

While the overall risk to the general population remains low thanks to strong childhood vaccination rates, declining adult booster coverage poses an emerging concern. Health authorities are urging clinicians to verify vaccination status and encourage booster immunisation, particularly among at-risk or underserved populations.

Cutaneous Diphtheria on the Rise

A multicentre retrospective study conducted in France (2018-2022) found that the recent resurgence of diphtheria has been accompanied by a predominance of skin infections rather than respiratory cases — a pattern confirmed across Europe in 2022, when 77% of reported infections were cutaneous.

These infections typically present with pustular, ulcerative, or necrotic lesions that develop on preexisting wounds and are often secondarily infected with Staphylococcus aureus or Streptococcus species.

The study identified several factors contributing to diagnostic challenges:

• Confusion with other bacterial skin infections, such as impetigo
• Positive cultures for the C diphtheriae complex that are sometimes dismissed as contamination
• Infrequent screening for nasopharyngeal carriage or eradication
• Limited case-tracking and reporting mechanisms

This diagnostic underestimation likely reflects low clinician awareness of cutaneous diphtheria and limited familiarity with national diagnostic guidelines. Health authorities in France and across Europe emphasise the need to raise clinical awareness of nonrespiratory diphtheria forms and encourage adherence to established diagnostic protocols.

Clinicians should suspect diphtheria in patients with chronic or worsening wounds, particularly following travel to endemic regions or among socially vulnerable individuals, such as the homeless or migrants.

Detection and Management Protocols

The management of suspected diphtheria requires strict compliance with public health protocols:

1. Sample collection: Obtain pharyngeal or skin swabs for culture and polymerase chain reaction (PCR) testing for the tox gene. If necessary, promptly forward isolates to the National Reference Center at Institut Pasteur for confirmation.
2. Isolation and infection control: Implement patient isolation and protective measures for healthcare staff until two negative samples — taken at least 24 hours apart — or 24 hours after treatment cessation.
3. Assessment for complications: Check for laryngeal, respiratory, or cardiac involvement, which may indicate systemic toxin effects.
4. Specific treatment:
   • Antibiotics: Use amoxicillin as first-line therapy or a macrolide in case of allergy, with routine susceptibility testing.
   • Equine antitoxin serum: Administer immediately in cases of typical diphtheria (ENT infection with positive PCR) or when toxin-mediated signs such as cardiac arrhythmias, conduction blocks, or descending paralysis occur in respiratory or cutaneous forms.
5. Contact tracing and prophylaxis: For all close contacts within the previous 7 days:
   • Clinical monitoring
   • Microbiological screening
   • Antibiotic prophylaxis
   • Vaccination update, if needed

This story was translated from Univadis France, part of the Medscape Professional Network.