NAME: Corynebacterium diphtheriae
SYNONYM OR CROSS REFERENCE: Diphtheria Footnote 1.
CHARACTERISTICS: Corynebacterium diphtheriae is part of the Corynebacteriaceae family and genus Corynebacterium. Bacteria are small, pleomorphic, aerobic, non-spore forming bacilli. They are Gram positive and slightly club shaped Footnote 1, Footnote 2. C. diphtheriae cells can be arranged as single cells, in pairs, in V forms, in palisades, or in clusters Footnote 2. They are non-motile and catalase positive Footnote 2. Non-hemolytic colonies appear within 18-24 hours when cultured on media containing blood at 37°C Footnote 1, Footnote 2. Biotypes (or biovars) of C. diphtheriae are gravis, mitis, belfanti and intermedius Footnote 1.
PATHOGENICITY/TOXICITY: C. diphtheriae is a causative agent of diphtheria (respiratory tract/pharyngreal/throat diphtheria or cutaneous diphtheria) Footnote 2.
Respiratory tract diphtheria: An upper respiratory tract illness which manifests as pharyngitis or tonsillitis with sore throat, dysphagia, lymphadenitis, low grade fever, malaise, and headache Footnote 1, Footnote 2. In severe cases, severe adenitis and soft tissue edema may result in bull neck appearance Footnote 3. A patch of membrane develops on the tonsils which may extend to tonsillar pillars, uvula, soft palate, oropharynx, and nasopharynx Footnote 1, Footnote 3. Edema and pseudomembrane coating of the trachea and bronchi can also occur Footnote 3. In uncomplicated cases, the disease usually resolves and the membrane is coughed up after 5-10 days Footnote 1. Serious effects of diphtheria such as myocarditis, neuritis, and kidney damage are caused by systemic absorption of the diphtheria exotoxin from the site of infection Footnote 1, Footnote 2, Footnote 4. Myocarditis is manifested by cardiac enlargement and weakness, arrhythmia and congestive heart failure Footnote 1. About 75% of patients with severe respiratory diphtheria may also develop neuropathy Footnote 3. Infection of the nervous system causes paralysis of the soft palate, or oculomotor muscles, which usually resolves with the formation of antitoxin antibody Footnote 1. Serious and lethal effects of diphtheria may also ensue from mechanical obstruction of the airway due to pseudomembrane extension into the trachea and bronchi, resulting in cyanosis and suffocation of the patient Footnote 1, Footnote 3.
Cutaneous diphtheria is most common in tropical, hot, and arid regions Footnote 4. It is characterized by formation of lesions on the skin, which may range from a simple pustule to a chronic non-recovering ulcer Footnote 1, Footnote 2, Footnote 3. C. diphtheriae mainly colonizes preexisting lesions on the skin such as surgical wounds, pyoderma, eczema, impetigo, dermatitis, or insect bites Footnote 3. Corynebacterium ulcerans and C. pseudotuberculosis can also harbour diphtheria tox genes and express diphtheria toxin. Infections by these species most often occur in animals but can also cause diphtheria-like disease in humans, with symptoms similar to those described here for C. diphtheriae. Of increasing concern are infections by toxigenic strains of C. ulcerans found in companion pets such as dogs or cats, which subsequently can cause zoonotic infections in humans Footnote 1.
EPIDEMIOLOGY: The WHO reported 7088 cases of diphtheria world wide in 2008 and 5000 estimated deaths in 2004 Footnote 5. Due to routine immunization programs, diphtheria is rare in developed countries, although, cases that are observed tend to be more serious, and may be fatal Footnote 4. In these countries, diphtheria usually occurs as small outbreaks in the unimmunized population such as among migrant workers or transients Footnote 1. In Canada, diphtheria has been limited to mainly small outbreaks in First Nations (i.e., indigenous North American Indian) populations, with the most recent outbreaks occurring over 30 years ago Footnote 6. Despite the widespread use of immunization, diphtheria remains endemic in developing countries such as India, Bangladesh, Vietnam, countries in Africa and areas of South America (i.e. Brazil) Footnote 7. In Russia, diphtheria remerged in 1990 and spread to all the other countries that previously formed the Soviet Union, as well as the Baltic States. The annual number of diphtheria cases was below 200 before 1990, and increased to 47,000 with 1700 deaths between 1990 and 1995, and approximately157,000 cases with 5000 deaths by the beginning of 1999 Footnote 1, Footnote 7.
HOST RANGE:Humans. Although rare, some biotypes of C. diphtheriae have also been isolated from animals such as cow, cats, and horses Footnote 8. C. ulcerans and C. pseudotuberculosis are derived from animals but also cause disease in humans Footnote 1.
INFECTIOUS DOSE: Unknown; however, the main virulence factor of Corynebacterium diphtheriae, C. ulcerans and C. pseudotuberculosis is diphtheria toxin, which has a lethal dose of < 0.1 µg/kg of body weight in humans Footnote 4, Footnote 9.
MODE OF TRANSMISSION: Transmission of C. diphtheriae can occur through droplet nuclei, fomites, and direct contact with cutaneous infections Footnote 1. C. diphtheriae has also been transmitted from hospital wards and clothing Footnote 10. Diphtheria has also been transmitted through the consumption of milk Footnote 11. Transmission of C. ulcerans and C. pseudotuberculosisis are thought to be similar to that of C. diphtheriae Footnote 1.
INCUBATION PERIOD: 2-4 days Footnote 1
COMMUNICABILITY: Variable period. In the absence of antibiotic therapy, disease is communicable for 2-4 weeks Footnote 10. Appropriate antibiotic therapy usually terminates bacterial shedding within 48 hours Footnote 10.
RESERVOIR: Humans are thought to be a significant reservoir for C. diphtheriae Footnote 10. C. diphtheriae may be present in nasopharynx and skin lesions for weeks to months or even for life time in asymptomatic individuals, which can act as a reservoir for the disease Footnote 1, Footnote 2. The reservoirs for C. ulcerans and C. pseudotuberculosis are thought to be primarily those of animals Footnote 1.
DRUG SUSCEPTIBILITY/ RESISTANCE: Susceptible to penicillin, erythromycin, tetracycline and certain cephalosporins Footnote 1, Footnote 12. Some strains resistant to erythromycin have been reported Footnote 12.
SUSCEPTIBILITY/RESISTANCE TO DISINFECTANTS: C. diphtheriae and related species can also be inhibited by chlorhexidine (MIC of 5mg/l) Footnote 13. Most vegetative bacteria are also susceptible to 1% sodium hypochlorite, 70% ethanol, glutaraldehyde, formaldehyde, iodines, hydrogen peroxide, peracetic acid, and quaternary ammonium compounds Footnote 14.
PHYSICAL INACTIVATION: Information specific to C. diphtheriae and related species is not available, but most vegetative bacteria can be inactivated by moist heat (121°C for 15 min- 30 min) and dry heat (160-170°C for 1-2 hours) Footnote 15.
SURVIVAL OUTSIDE HOST: C. diphtheriae can survive on dry inanimate surfaces from 7 days to 6 months Footnote 16. Survival of C. ulcerans and C. pseudotuberculosis is unknown.
SURVEILLANCE: Monitor for symptoms. Diagnosis of diphtheria is done mainly through monitoring of clinical symptoms (lesions on the skin or formation of pseudomembrane) Footnote 1, Footnote 2. Confirmation of C. diphtheriae infection can be done by culture of the bacteria on selective media such as 5% sheep blood agar, tinsdale medium, and colistin-nalidixic acid blood agar, followed by Gram staining, and differential biochemical tests Footnote 1, Footnote 2. Other methods for identification of these species include: gas-liquid chromatography of cellular fatty acids, and increasingly, the use of 16SrRNA and rpoB gene sequencing Footnote 2.
Note: All diagnostic methods are not necessarily available in all countries.
FIRST AID/TREATMENT: Administration of diphtheria antitoxin (DAT) is the most successful treatment for diphtheria Footnote 4. In order to prevent further toxin production, antibiotic therapy with penicillins, cephalosporins, erythromycin, and tetracycline may be used in conjunction with antitoxin to eliminate the bacteria from the site of infection Footnote 1, Footnote 4, Footnote 10. Penicillin can be given intramuscularly or orally Footnote 10.
IMMUNIZATION: Vaccination for the control of diphtheria infection is given as a combined DTaP vaccine of Diphtheria, pertussis, and tetanus toxoid Footnote 17, Footnote 18. It is administered along with the vaccine for poliomyelitis and Haemophilus influenzae type b (DTaP-IPV-Hib) at 2, 4, 6 and 18 months of age Footnote 18, Footnote 19. A booster dose of DTaP–IPV vaccine is also given between 4 and 6 years of age Footnote 18. A single booster dose of dTpa (Boostrix TM) can be also be used to prevent diphtheria, tetanus, and pertussis in individuals more than 4 years of age in Europe and Canada, in adolescents aged 10–18 years in the US, and in individuals over the age of 10 in Australia Footnote 17. This vaccine contains the same toxoid as DTap vaccine, and is used for primary immunization, but in reduced quantities to prevent increased immunological reactions with consecutive doses Footnote 17. Individuals should be boosted every 10 years after conclusion of childhood vaccination regime Footnote 20.
PROPHYLAXIS: Antibiotic prophylaxis with intramuscular benzathine penicillin G is recommended for close household contacts and medical staff exposed to oral secretions of the infected individual. Oral erythromycin can also be used Footnote 10.
LABORATORY-ACQUIRED INFECTIONS: Thirty-three cases of laboratory acquired diphtheria were reported as of 1976 Footnote 21.
PRIMARY HAZARDS: Inhalation, accidental parenteral inoculation, and ingestion Footnote 22.
SPECIAL HAZARDS: None.
RISK GROUP CLASSIFICATION: Risk Group 2 Footnote 23.
CONTAINMENT REQUIREMENTS: Containment Level 2 facilities, equipment, and operational practices for work involving infected or potentially infected materials, animals, or cultures Footnote 24.
PROTECTIVE CLOTHING: Lab coat. Gloves when direct skin contact with infected materials or animals is unavoidable. Eye protection must be used where there is a known or potential risk of exposure to slashes Footnote 24.
OTHER PRECAUTIONS: All procedures that may produce aerosols, or involve high concentrations or large volumes should be conducted in a biological safety cabinet (BSC). The use of needles, syringes, and other sharp objects should be strictly limited. Additional precautions should be considered with work involving animals or large scale activities Footnote 24.
SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply an appropriate disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up Footnote 24.
DISPOSAL: Decontaminate all wastes that contain or have come in contact with the infectious organism by autoclave, chemical disinfection, gamma irradiation, or incineration before disposing Footnote 24.
STORAGE: The infectious agent should be stored in leak-proof containers that are appropriately labeled Footnote 24.
REGULATORY INFORMATION: The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.
UPDATED: December 2011
PREPARED BY: Pathogen Regulation Directorate, Public Health Agency of Canada
Although the information, opinions and recommendations contained in this Pathogen Safety Data sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.
Public Health Agency of Canada, 2011