Diphtheria (Corynebacterium diphtheriae)
2019 Case Definition

Background

Diphtheria is caused by toxin-producing Corynebacterium diphtheriae (C. diphtheriae). This disease primarily manifests as respiratory infections that may result in death, but it may also present as mild infections in non-respiratory sites, such as the skin. While respiratory diphtheria is now extremely rare, non-respiratory infections caused by toxin-producing bacteria have recently been detected. Non-respiratory disease caused by toxin-producing C. diphtheriae may act as a source of transmission and can lead to new respiratory and non-respiratory diphtheria disease; both respiratory and non-respiratory disease caused by toxin-producing bacteria require public health follow-up. This diphtheria surveillance case definition better reflects the epidemiology of diphtheria in the U.S, in order to focus efforts on identifying disease caused by toxin-producing bacteria and appropriately guide public health interventions.

Clinical Criteria

• Upper respiratory tract illness with an adherent membrane of the nose, pharynx, tonsils, or larynx
  OR
• Infection of a non-respiratory anatomical site (e.g., skin, wound, conjunctiva, ear, genital mucosa)

Laboratory Criteria For Diagnosis

Confirmatory laboratory evidence:

• Isolation of C. diphtheriae from any site AND
• Confirmation of toxin-production by Elek test or by another validated test capable of confirming toxin-production

Supportive laboratory evidence:

• Histopathologic diagnosis

Epidemiologic Linkage

Epidemiologic linkage requires direct contact with a laboratory-confirmed case of diphtheria.

Criteria to Distinguish a New Case from an Existing Case

Individuals without evidence of clinical criteria as described by the diphtheria surveillance case definition but for whom toxin-producing Corynebacterium 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.

Suspected

• • 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 toxin-producing 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 toxin-producing C. diphtheriae from that site

Case Classification Comments

• 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.

• Diphtheria (Corynebacterium diphtheriae) | 2010 Case Definition
• Diphtheria (Corynebacterium diphtheriae) | 1995 Case Definition
• Diphtheria (Corynebacterium diphtheriae) | 1990 Case Definition