Epidemiology and Trends of Corynebacterium diphtheriae in the United States, 2016—2023

Background Diphtheria, commonly resulting in severe respiratory or cutaneous disease, is caused by toxigenic strains of Corynebacterium diphtheriae; non-toxigenic strains can also cause disease. In the United States, only toxigenic disease is reportable, and the Centers for Disease Control and Prevention (CDC) perform the only Elek testing to confirm diphtheria toxin production. We examine the epidemiology, toxigenicity, and trends of C. diphtheriae isolates reported during 2016—2023 in the United States. Methods C. diphtheriae isolates submitted to CDC were cultured and tested by PCR and Elek. Laboratory and epidemiological data were linked; we conducted descriptive statistics by toxigenicity status. Results A total of 1155 C. diphtheriae isolates were submitted during 2016—2023; 96.1% (n=1110) were non-toxigenic, 3.0% (n=35) were non-toxigenic tox-bearing (NTTB), and 0.9% (n=10) were toxigenic. From 2016 to 2023, the annual number of reported isolates increased over 10-fold. Median patient age was 43 years (range: <1-98), and 68.6% (n=793) were male. Isolates were primarily obtained from cutaneous sites (69.8%, n=806). Risk factors for non-toxigenic and NTTB infections included housing instability and history of intravenous drug use. Nine of the 10 toxigenic isolates were from patients with recent international travel to a diphtheria-endemic country, and none were from patients with respiratory symptoms. Conclusions There has been an increase in C. diphtheriae isolates identified in the United States. However, toxigenic cases remained infrequent and risk factors appear to differ between patients with toxigenic compared with non-toxin producing infections. Risk factor awareness may help to guide public health intervention prior to confirmation of toxigenicity.