Diphtheria

Before the introduction of vaccines 60 years ago, diphtheria was a leading cause of childhood death around the world. In 2018, countries reported more than 16,000 cases of diphtheria to the World Health Organization (WHO), and there are likely many more cases. The case fatality rate is up to 50 per cent without treatment and even with treatment, case fatality ratios up to 10 per cent have been reported in diphtheria outbreaks.

The following are standard case definitions to allow national health authorities to interpret data in an international context. However, during an outbreak case definitions may be adapted to the local context and the Red Cross Red Crescent should use those agreed/established by national health authorities. NB: Consider that during community-based surveillance, volunteers should use broad (simplified) case definitions (also known as community case definitions) to recognize people exhibiting the signs and symptoms matching diphtheria and encourage them to seek care. Other actors such as healthcare workers or investigators studying the cause of a disease, on the other hand, can use more specific case definitions that may require laboratory confirmation.

Globally, diphtheria has become rare and therefore the World Health Organization recommends that surveillance is case-based; that is, providers that identify cases should be required to report those cases immediately, ideally accompanied by laboratory case confirmation. That said, during large outbreaks, case-based surveillance may not be feasible if laboratory testing is logistically challenging and clinical diagnosis may be used to identify associated cases.

Suspected case definition: pharyngitis, nasopharyngitis, tonsillitis or laryngitis AND adherent pseudomembrane in the throat or nose. A diphtheria pseudomembrane is an exudate that is greyish, thick and firmly adherent. Dislodging the pseudomembrane is likely to cause profuse bleeding.

Confirmed case definition: laboratory-confirmed classic respiratory diphtheria cases meet suspected case definition. Non-respiratory laboratory-confirmed diphtheria cases have a skin lesion or non-respiratory mucosal infection

WHO, 2018 Diphtheria. Available at: https://cdn.who.int/media/docs/default-source/immunization/vpd_surveillance/vpd-surveillance-standards-publication/who-surveillancevaccinepreventable-04-diphtheria-r2.pdf?sfvrsn=3840f49a_10&download=true

WHO case definition: https://www.who.int

A single laboratory-confirmed case of diphtheria should trigger a public health response. Two temporally and geographically linked cases, of which at least one is laboratory-confirmed, is considered an outbreak of diphtheria.

• Any non-immune person (either not vaccinated or did not develop immunity after vaccination) can become infected.
• Diphtheria outbreaks can be particularly deadly in countries experiencing or recovering from a natural disaster or conflict. Damage to health infrastructure and health services interrupts routine immunization and overcrowding in residential camps greatly increases the risk of infection.
• Overcrowded areas where a person-to-person spread is easily possible.
• Migrants or refugee populations are at increased risk to become infected because of crowded living conditions and missing of routine immunization programmes.
• Lack of proper sanitation and hygiene measures.

Attack rates will vary from one outbreak to another. In case of an outbreak, consult the latest information provided by health authorities.

A retrospective study in Bangladesh showed that the attack rate depended on the degree of diphtheria vaccination in a population. The crude attack rate of a large outbreak of diphtheria among the Rohingya population in Cox’s Bazar, Bangladesh from 2017 to 2019 was 51.5 cases per 10,000 person-years.

• Persons younger than 5 years of age.
• Persons older than 40 years of age.
• People with underlying medical problems like high blood pressure, cardiovascular disease, diabetes, chronic respiratory disease, chronic kidney disease, chronic infectious diseases, cancer and obesity.
• People who are immunosuppressed such as those receiving chemotherapy, transplant recipients or HIV carriers.

Toxin (poison)-producing Corynebacterium diphtheriae (C. diphtheriae)

Two other Corynebacterium species (C. ulcerans and C. pseudotuberculosis) may produce diphtheria toxin; both species are zoonotic but no person-to-person spread has been documented.

Humans.

Only for C. ulcerans and C. pseudotuberculosis zoonotic disease: animals.

• Airborne and droplet spread: sneezing, coughing, talking and droplet nuclei in the air transmit C. diphtheriae. Sharing eating and drinking utensils can increase droplet spread. Objects like contaminated bedding can also lead to transmission.
• Contact transmission: People can also get sick from touching infected open sores or ulcers from someone with cutaneous diphtheria.

Two to five days (range 1–10 days).

A person is infectious as long as virulent bacteria are present in respiratory secretions, usually two weeks without antibiotics, seldom more than six weeks. In rare cases, chronic carriers may shed organisms for six months or more.

Respiratory diphtheria: The most common and most severe type of diphtheria, whereby the exotoxin produced causes the formation of a membrane of dead tissue in the throat and over the tonsils, making breathing and swallowing difficult. It can cause weakness, sore throat, mild fever, swollen glands in the neck. The exotoxin damages other organs as well when getting into the blood stream, often resulting in complications such as heart failure, nerve damage, loss of the ability to move (paralysis), kidney damage and death, even with treatment. Without treatment, up to half of patients can die from the disease.

Cutaneous diphtheria: More rarely (up to 2 per cent of all diphtheria cases), it can affect mucous membranes at other non-respiratory sites, such as genitals and conjunctiva (membrane covering the eye and the inside of eyelids), causing open sores or ulcers. However, cutaneous diphtheria rarely results in any other severe disease.

Influenza, parotitis due to other causes, COVID-19 disease, pertussis, measles, other infections of the respiratory tract. Non-infectious diseases like exacerbated chronic respiratory diseases or allergies.

Swabbing the back of the throat or nose or an open ulcer and laboratory testing for C. diphtheriae. It is important to start treatment right away if there is suspicion of diphtheria as laboratory findings can take some time.

Please refer to the appropriate local or international guidelines for clinical management. All clinical management including the administration of a treatment or vaccine should be conducted by a health professional.

All suspect diphtheria cases require isolation, collection of nasal and pharyngeal swabs and culture, Diphtheria Antitoxin Treatment (DAT) and antibiotic treatment.

Diphtheria toxoid, the vaccine to prevent diphtheria, should be given to infants as a primary series of three doses, followed by three appropriately spaced booster doses to ensure long-term protection. Diphtheria vaccines are commonly available in combination with other vaccines such as pertussis and tetanus.

Protective immunity does not always develop after recovery from disease. Therefore, individuals recovering from diphtheria should complete the diphtheria toxoid vaccination during convalescence.

Vaccination schedule needs booster doses to ensure long-term protection.