Surveillance

Although state health departments now rarely report diphtheria in the United States, the disease was one of the most common causes of illness and death among children before a vaccine was available. Since the introduction of diphtheria vaccines, which began in the 1920s and 1930s, and implementation of universal childhood vaccination in the late 1940s, diphtheria has been well-controlled in the United States. However, the disease continues to cause illness globally and there have been outbreaks reported in recent years. In 2020, the World Health Organization reported 10,107 global cases of diphtheria. While this was a decline in the number of cases compared to previous years, the decrease was likely impacted by the COVID-19 pandemic.

Case definition

The Council of State and Territorial Epidemiologists revised the following case definition for diphtheria and published it in 2019.

Suspect

• In the absence of a more likely diagnosis, an upper respiratory tract illness with each of the following:
  • An adherent membrane of the nose, pharynx, tonsils, or larynx AND
  • Absence of laboratory confirmation AND
  • Lack of epidemiologic linkage to a laboratory-confirmed case of diphtheria

OR

• Histopathologic diagnosis

Confirmed

• An upper respiratory tract illness with an adherent membrane of the nose, pharynx, tonsils, or larynx and any of the following:
  • Isolation of Corynebacterium diphtheriae from the nose or throat OR
  • Epidemiologic linkage to a laboratory-confirmed case of diphtheria

OR

• An infection at a non-respiratory anatomical site (e.g., skin, wound, conjunctiva, ear, genital mucosa) with
  • Isolation of diphtheriae from that site

Comments:

• Individuals without evidence of clinical criteria as described by the diphtheria surveillance case definition but for whom toxin-producing C. diphtheriae is confirmed via laboratory testing (isolation and toxigenicity testing by modified Elek test or other validated test capable of confirming toxin-production) should not be classified as cases. These individuals are considered carriers of the bacteria and are not reportable.
• Cases of laboratory-confirmed, non-toxin-producing C. diphtheriae (respiratory or non-respiratory) should not be reported by state or local health departments to CDC as diphtheria cases.
• Negative laboratory results may be sufficient to rule out a diagnosis of diphtheria; however, clinicians should carefully consider all lab results in the context of the patient’s vaccination status, antimicrobial treatment, and other risk factors.
• PCR (polymerase chain reaction) and MALDI-TOF (matrix assisted laser desorption/ionization-time of flight mass spectrometry) diagnostics for C. diphtheriae, when used alone, do not confirm toxin production. These tests, when used, should always be combined with a test that confirms toxin production, such as the Elek test.

Reporting to CDC

Healthcare professionals should promptly report suspected diphtheria cases to their respective health department and then the CDC Emergency Operations Center (770-488-7100) to obtain diphtheria antitoxin for treating the patient. A Food and Drug Administration-licensed diphtheria antitoxin product is no longer available commercially in the United States. However, diphtheria antitoxin is available from CDC under an Investigational New Drug (IND) protocol. Healthcare professionals must provide additional epidemiologic and clinical data to receive diphtheria antitoxin under the IND.

Healthcare professionals should notify their state health department promptly so they can promptly initiate an epidemiologic investigation. The state health department is responsible for reporting suspect and confirmed cases to the National Notifiable Diseases Surveillance System. Health departments should not delay reporting because of incomplete information or lack of laboratory confirmation.