Diphtheria on the rise

Global diphtheria is in a phase of renewed concern, characterized by persistent endemic transmission in low‑resource settings, large multi‑country outbreaks, and smaller clusters in high‑income regions, all occurring against a backdrop of incomplete vaccination coverage and strained clinical and antitoxin capacity.

According to WHO, an estimated 84% of the world’s children received three doses of a diphtheria‑containing vaccine in 2023, leaving roughly 16%—tens of millions of children—either unvaccinated or under‑vaccinated. These immunity gaps are concentrated in fragile and conflict‑affected countries, urban slums, and mobile or marginalized populations, where routine immunization systems have not fully recovered from COVID‑19 disruptions. Recent WHO guidance emphasizes that un‑ or incompletely immunized individuals remain at substantial risk, with untreated case‑fatality rates of up to 30% in naïve patients and the highest mortality among young children. At the same time, global supplies of diphtheria antitoxin (DAT) remain limited, prompting WHO to issue new clinical management and DAT‑use guidelines and to call for prioritized allocation and earlier clinical recognition in outbreak settings.

The most dramatic epidemiologic shift is in the WHO African Region, where, since 2023, large outbreaks have been reported from multiple countries in West and Central Africa and have continued into 2025. WHO situation reports describe tens of thousands of suspected and confirmed cases with case‑fatality ratios typically between about 3–6%, with deaths driven by delayed care, lack of DAT, and co‑morbid malnutrition or concurrent infections. Cases cluster predominantly in children and adolescents, but young adults are increasingly affected, reflecting immunity gaps after childhood and missed booster doses. Transmission patterns are mixed: classic respiratory diphtheria in crowded households and schools, and cutaneous diphtheria in settings with poor hygiene and high burden of skin trauma. WHO now explicitly recommends life‑course immunization strategies (routine primary series plus three boosters, and decennial Td/Tdap boosters in adulthood) to prevent waning immunity, particularly in high‑risk regions and occupational groups.

In the European Union/European Economic Area, ECDC data show that diphtheria remains rare but not negligible, with 216 cases due to toxigenic Corynebacterium diphtheriae or C. ulcerans reported in 2023. Most cases were cutaneous C. diphtheriae in migrants, asylum seekers, and other vulnerable groups, although a smaller number of classic respiratory cases—and a few deaths—occurred. Since late 2022, a particular sequence type (ST574) has caused a prolonged multi‑country cutaneous outbreak, with documented circulation through at least five EU/EEA countries and continued low‑level transmission into 2025 despite targeted public health measures. Vaccination status was known for only 44% of EU/EEA cases in 2023, and among these, about two‑thirds were unvaccinated or incompletely vaccinated, highlighting pockets of susceptibility even in settings with generally high national DTP3 coverage. ECDC notes that DTP3 coverage has declined between 2019 and 2023 in several EU countries, underscoring the need for renewed focus on childhood and booster vaccination, especially in migrant reception centers, prisons, and homeless populations.ecdc.europa+3

Beyond Africa and Europe, national and regional public health agencies, including CDC and allied centers, have documented substantial diphtheria activity in parts of Asia and the Americas, often in association with humanitarian crises, displacement, and travel. Risk assessments emphasize that highly vaccinated populations remain broadly protected, but importations via travel and migration can seed outbreaks in under‑immunized subgroups if clinical suspicion, laboratory capacity, and access to DAT are inadequate. In response, WHO and ECDC both stress early case recognition, rapid laboratory confirmation, prompt DAT plus antibiotic treatment, and ring or targeted vaccination around clusters. Recent WHO guidelines recommend macrolides (azithromycin or erythromycin) over penicillin as first‑line antibiotics for suspected or confirmed cases, in part to address emerging resistance patterns and to simplify standard regimens.

Taken together, the contemporary global diphtheria situation is best understood as a convergence of three trends:

• large, high‑impact outbreaks in African and some Asian settings where zero‑dose and under‑immunized children remain numerous;
• persistent, low‑level but expanding transmission in high‑income regions within marginalized populations; and
• health‑system constraints, notably DAT shortages and limited laboratory capacity, that increase morbidity and mortality when outbreaks occur.

Addressing these challenges will require sustained investment in routine immunization and booster programs, targeted catch‑up campaigns, better surveillance and sequencing of Corynebacterium diphtheriae, and international coordination to secure and rationally deploy DAT and updated clinical tools. I am afraid to say that this will not happen appropriately.

By Prof. Joe Schmitt — Editor-in-Chief, Global Health Press