By Stan Deresinski, MD, FACP, FIDSA
Synopsis: A marked increase in cases of diphtheria in Europe is related to migrants, most often from Syria or Afghanistan, indicating a need to maintain high levels of immunity through vaccination, not only in Europe but everywhere, including the United States.
Source: Hoefer A, Seth-Smith H, Palma F, et al; 2022 European Diphtheria Consortium. Corynebacterium diphtheriae outbreak in migrant populations in Europe. N Engl J Med. 2025; Jun 4. doi: 10.1056/NEJMoa2311981. [Online ahead of print].
The mean annual number of cases of diphtheria reported to the European Centre for Disease Prevention and Control between 2016 and 2021 was 27, but this number surged in several European countries in 2022. In January through November 2022, a total of 363 toxigenic Corynebacterium diphtheriae isolates were recovered from 362 patients in 10 countries. The countries with the most reported cases were Germany, which accounted for 118 patients, Austria (66), the United Kingdom (59), and Switzerland (52). Countries of origin were known for 266 patients, and for 222 (83.5%) the origin country was either Afghanistan or Syria, with the remaining 44 originating in one of 17 other countries. In addition, there were 26 transit countries, mostly in the western Balkans.
The median age of the patients was 18 years; of the 362 cases, 348 (96.1%) had a history of recent migration, contact with a migrant population, or recent entry into the reporting country. Of the 346 patients for whom clinical data were available, 268 (77.5%) had cutaneous diphtheria, 53 (15.3%) had respiratory diphtheria (including 11 [3.2%] with pseudomembrane formation), and nine (2.6%) had respiratory and cutaneous disease. Three patients had genital infection.
Vaccination history was unknown for 290 patients, while four patients were known to have been vaccinated and 10 were not previously vaccinated. A variety of antibiotics were administered to the patients, 17 of whom were reported to have been hospitalized. All 12 patients hospitalized with respiratory diphtheria were treated with antitoxin in addition to antibiotics.
The isolates were multiclonal. Among those tested, 99.7% were susceptible to penicillin, 93.6% were susceptible to erythromycin, and only one isolate was resistant to both erythromycin and beta-lactams. Resistance was common with trimethoprim-sulfamethoxazole (81.1%), tetracycline (32.8%), and ciprofloxacin (22.4%). One patient, who had extensive pseudomembranes and whose receipt of antitoxin was delayed, died.
Commentary
The fact that only one of the patients died is remarkable. In addition to airway involvement, potentially lethal disease may result from systemic absorption of diphtheria toxin, which may adversely affect the myocardium, central nervous system, and kidneys.
Another remarkable observation in this study was the fact that all but 1.9% of reported cases occurred in males. This extraordinary proportion can be speculated to be due to behavioral differences, including in healthcare-seeking behavior in males compared to females in the at-risk groups.
The response to the surge in diphtheria in Europe included contact tracing and screening for identification of secondary cases. Some countries administered chemoprophylaxis to contacts, while others initiated vaccine campaigns and wider chemoprophylaxis directed at migrant centers. Hoefer and colleagues provided a broader potential range of public health measures.
It is likely the cases identified in this study represent an underestimate. Only a very small proportion of patients were reported to have been vaccinated, but for most the information was unavailable. Lack of immunity also may occur in individuals vaccinated as children, since antibody levels wane over time. Berbers and colleagues tested > 10,000 serum samples from individuals who were 40-59 years of age in 18 European countries between 2015 and 2018 and found that 22.8% to 82.0% had antibody levels that were < 0.1 IU/mL.1 In England, 26% of individuals > 70 years of age lacked protective antibody levels.2
The Centers for Disease Control and Prevention indicates that there were only five cases of toxigenic C. diphtheriae infection in the United States in 2018-2022, although there has been an increase in non-toxin-producing strains. Nonetheless, maintaining a level of alertness is critical.
Stan Deresinski, MD, FACP, FIDSA, is Clinical Professor of Medicine, Stanford University.
References
1. Berbers G, van Gageldonk P, van de Kassteele J, et al; Serosurveillance Study Team. Circulation of pertussis and poor protection against diphtheria among middle-aged adults in 18 European countries. Nat Commun. 2021;12(1):2871.
2. Vusirikala A, Tonge S, Bell A, et al. Reassurance of population immunity to diphtheria in England: Results from a 2021 national serosurvey. Vaccine. 2023;41(46):6878-6883.
A marked increase in cases of diphtheria in Europe is related to migrants, most often from Syria or Afghanistan, indicating a need to maintain high levels of immunity through vaccination, not only in Europe but everywhere, including the United States.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content