BACKGROUND: Diphtheria is a vaccine-preventable disease caused by toxigenic Corynebacterium diphtheriae. Treatment with equine diphtheria antitoxin (DAT) is effective against disease progression and complications but globally, availability of DAT is tenuous. Although vaccination has led to substantial declines in diphtheria incidence worldwide, diphtheria continues to be endemic in some non-industrialized countries. Additionally, indigenous diphtheria cases were recently reported from developed Western European countries despite high vaccination coverage. In the United States, respiratory diphtheria, fulfilling the CSTE case definition for diphtheria, is a notifiable disease. Since 1996, an unlicensed DAT product is available from CDC under an FDA-approved Investigational New Drug protocol. We evaluated trends in reported diphtheria cases, vaccination coverage, and characterization of isolates submitted to CDC, and assessed sources of DAT manufacture globally.
METHODS: We identified diphtheria cases reported to the National Notifiable Diseases Surveillance System (NNDSS) from 1996–2016. Cases reported to NNDSS with incomplete laboratory results were cross-checked with specimens sent to CDC for culture and toxigenicity testing. Data from National Immunization Surveys conducted from 1996 were reviewed to determine diphtheria vaccine coverage trends. Toxigenicity of C. diphtheriae isolates submitted to CDC during this time period (including isolates from non-reportable cases and non-human sources) was evaluated. Current global manufacturers and exporters of DAT were identified through web searches and direct communication with manufacturers.
RESULTS: Thirteen respiratory diphtheria cases were reported to NNDSS from 1996-2016; two of these were reported since 2004. Specimens from eleven reported cases were sent to CDC for testing. C. diphtheriae was cultured from four specimens; only one isolate, from a case in 1996, was toxigenic. Seven specimens with negative culture results were positive by PCR testing for diphtheria tox gene. Toxigenic C. diphtheriae was also isolated from specimens submitted from ten non-reportable respiratory illnesses and one cutaneous case with recent international travel history. Additionally, six equine C. diphtheriae isolates sent to CDC, the most recent in 2016, were confirmed as toxigenic. Childhood vaccination with the primary series of a diphtheria vaccine has remained above 90% since 1996. Globally, DAT is currently only exported by one manufacturer.
CONCLUSIONS: Diphtheria is rare in the United States as a result of high vaccination coverage, but human and nonhuman circulation of toxigenic C. diphtheriae is still occurring. Given the possibility of importation of diphtheria from endemic countries, it is important to ensure continued high immunization coverage for herd protection and DAT availability for treatment.