Diphtheria, from the Greek word for "leather" (describing the appearance of the membranes that form in patients), is an infection caused by a Corynebacterium from the diphtheriae complex (the taxonomic group comprising Corynebacterium diphtheriae, Corynebacterium belfantii, Corynebacterium ulcerans and Corynebacterium pseudotuberculosis). Some strains of these bacterial species may carry the tox gene (which encodes the diphtheria toxin) and are therefore capable of producing the diphtheria toxin, which is responsible for severe clinical manifestations of diphtheria.
The typical manifestation of diphtheria is an infection of the upper respiratory tract which can result in paralysis of the central nervous system or of the diaphragm and throat, leading to death by suffocation. C. diphtheriae infection is highly contagious. Diphtheria is spread through the air from direct contact with patients or healthy carriers. Infection with C. ulcerans is transmitted by ingesting raw milk contaminated with the bacterium or coming into contact with pets, especially dogs or cats, which themselves are often asymptomatic. Human-to-human transmission has never been demonstrated for cases of infection with C. ulcerans. Infection with C. pseudotuberculosis is very rare and is usually caused by contact with goats.
The incubation period for diphtheria is generally between 2 and 5 days. The most characteristic symptom is the formation of a "pseudomembrane", a grayish-white coating around the tonsils or the skin lesions. Respiratory diphtheria, the most common form of the disease, is characterized by sore throat, fever, a swollen neck and headache. The very rare cases of infection by C. pseudotuberculosis particularly attack the lymph nodes (necrotizing lymphadenitis).
Surveillance of diphtheria in France is based on the obligation to report all cases. Good vaccine coverage has brought the disease under control in France. The most recent reported indigenous case caused by C. diphtheriae was in 1989. Between 2011 and 2018, 33 cases of infection by C. diphtheriae strains carrying the tox gene were observed. All were either imported cases or cases detected in overseas France, in subjects who had been only partially vaccinated or not vaccinated at all. Most cases were cutaneous diphtheria. None of the patients died. During the same period, 43 cases of infection with C. ulcerans strains carrying the tox gene were reported in mainland France. Most of these cases were again cutaneous diphtheria, like those caused by C. diphtheriae. But all the cases were indigenous, and four of the patients died from their infection. A common feature of the C. ulcerans infections was that the patients had come into contact with pets.
Treatment for typical diphtheria involves administering diphtheria antitoxin serum by intramuscular injection as soon as possible, and/or a course of antibiotics. Antibiotic therapy with amoxicillin is recommended, or therapy with macrolides if the patient is allergic to beta-lactam antibiotics. More information is available on the website of the National Reference Center (CNR) for Corynebacteria of the Diphtheriae Complex and in the guidelines published by the French High Council for Public Health (HCSP) on how to deal with a case of diphtheria.
The diphtheria vaccine is the only way of controlling this severe infection. The vaccine is composed of purified, inactivated diphtheria toxin. Vaccination is compulsory for all children and healthcare professionals. Primary vaccination is now compulsory for infants at the age of 2 and 4 months. The first booster is given at 11 months and further boosters are given at ages 6, 11-13, 25, 45 and 65, then every 10 years. Seroprevalence studies carried out since 1998 indicate that several individuals aged 50 or over in France have an antibody titer that is undetectable or under the level considered to offer protection. These data emphasize the importance of following vaccine recommendations, especially boosters every 10 years in adults over the age of 65.
At Institut Pasteur
The National Reference Center (CNR) for Corynebacteria of the Diphtheriae Complex is hosted in the Biodiversity and Epidemiology of Bacterial Pathogens Unit at the Institut Pasteur. The CNR is responsible for maintaining microbiological expertise about C. diphtheriae, C. ulcerans and C. pseudotuberculosis (and also C. belfantii, a new species recently described by this team).
Biodiversity and Epidemiology of Bacterial Pathogens Unit led by Sylvain Brisse
Surveillance and public health
National Reference Center for Corynebacteria of the Diphtheriae Complex led par Sylvain Brisse
Illustration - Copyright Institut Pasteur
Caption - The crystal structure of diphteria toxin