[Table of Contents]

Volume: 24S3 - July 1998

Guidelines for the Control of Diphtheria in Canada

GUIDELINES FOR MANAGEMENT OF CASES AND PREVENTION OF SECONDARY TRANSMISSION

The appropriate management of diphtheria includes the prompt recognition of cases, early treatment, and the timely institution of control measures to prevent secondary cases. The following guidelines are based on previous publications^{(4, 24-27)}.

Diagnosis of cases

Clinical diagnosis

Early recognition is essential to the successful management of diphtheria cases and timely institution of control measures. A high index of suspicion is required for prompt diagnosis for several reasons: respiratory diphtheria may progress rapidly, antitoxin is effective only against circulating toxin (not bound to tissues), and diphtheria is currently very rare in Canada and considered to be eliminated in many parts of the country.

A clinical suspicion of diphtheria should be raised by a presentation of an upper respiratory tract illness (laryngitis, nasopharyngitis, or tonsillitis) with low-grade fever, enlarged anterior cervical lymph nodes, and a grayish adherent membrane of the nose, tonsils, pharynx, and/or larynx. Although a membrane is considered typical of diphtheria, it is not always present.

Diphtheria should also be considered in the differential diagnosis of bacterial and viral pharyngitis, Vincent's angina, infectious mononucleosis, adenovirus infections, peritonsillar abscess, oral syphilis, and candidiasis^(3,4).

Laboratory investigation

The laboratory should be notified as soon as the diagnosis is suspected since the successful isolation of C. diphtheriae depends on the rapid inoculation of special culture media. Throat and nasopharyngeal swabs should be taken for culture before antibiotic therapy is initiated. Do not wait for results before treatment; confirmatory diagnosis requires culture and isolation of the organism, biochemical typing, and toxigenicity testing, and may take several days⁽²⁴⁾. Culturing of samples from both nasal and pharyngeal sites may improve the rate of isolation of C. diphtheriae although nasal diphtheria in the absence of pharyngeal involvement is uncommon⁽²⁴⁾. If a membrane is present, samples should be taken from the membrane or beneath its edge. Laboratory guidelines for the current identification techniques for C. diphtheriae and directions for proper specimen collection are outlined in Appendix B.

The measurement of antibodies to diphtheria antitoxin in a serum sample taken before administration of antitoxin may be useful in supporting the diagnosis - when the cultures are negative - if a non-protective level (< 0.01 IU/mL) is demonstrated.

Management of cases

Patients with suspected respiratory diphtheria should be treated on clinical grounds. Therapy should not be delayed until bacteriologic confirmation is obtained. Antitoxin therapy is considered the mainstay of treatment while antibiotic therapy is required to eradicate the organism and prevent spread.

Diphtheria antitoxin

Prompt administration of antitoxin is essential as the antitoxin will only neutralize circulating toxin that is not yet bound to tissue. Delayed administration increases the risk of late effects such as myocarditis and neuritis. A single dose of' diphtheria antitoxin should be administered even before culture results are available. Antitoxin dosage depends on the site and extent of the diphtheritic membrane, the degree of toxicity, and the duration of illness. Table 1 presents recommended doses and modes of administration^(25,27). Consult product monographs for additional specifications. Diphtheria antitoxin is available through the Emergency Drug Release Program of LCDC as outlined in Appendix C.

As diphtheria antitoxin is of equine origin, all patients should be tested for sensitivity to horse serum before administration of antitoxin, and if necessary desensitized. The administration of equine antitoxin under the protection of a desensitization procedure must be continuous because protection from desensitization is lost once administration is interrupted⁽²⁶⁾. Therefore, all efforts should be made to obtain sufficient antitoxin before treatment is started. Refer to the Red Book: Report of the Committee on Infectious Diseases⁽²⁶⁾ or other clinical texts for a guide on sensitivity tests. Ensure that epinephrine is readily available for use if acute anaphylaxis develops.

Antibiotics

Antibiotic treatment is needed to eliminate the organism and prevent spread. Antibiotic treatment is not a substitute for antitoxin. Laboratory specimens should be collected before antibiotics are started. Recommended regimens for the antibiotics of choice, erythromycin and penicillin, are procaine penicillin G given intramuscularly (25,000 units/kg daily to 50,000 units/kg daily for children and 1.2 million units/kg daily for adults, in two divided doses) or a parenteral course of erythromycin (40 units/kg daily to 50 mg/kg daily, with a maximum of 2 g/d) until the patient can swallow comfortably; then erythromycin orally (40 units/kg daily to 50 mg/kg daily, with a maximum of 2 g/d, in four divided doses), or penicillin V may be substituted (125 mg to 250 mg four times daily) and given orally for a total treatment period of 14 days.

Elimination of C. diphtheriae should be confirmed by two negative cultures of throat and nasopharyngeal swabs taken at least 24 hours apart and a minimum of 2 weeks after antibiotic treatment is completed. Persistent carriage of the organism should be treated with an additional 10-day oral course of erythromycin with follow-up cultures.

Isolation

Standard and droplet precautions (see Appendix D) should be observed for all patients with respiratory diphtheria until two negative cultures are obtained of throat and nasopharyngeal swabs taken at least 24 hours apart and at least 2 weeks after completion of antibiotic treatment.

Immunization Patients convalescent from diphtheria should be given a complete primary course of toxoid, as indicated by age, unless serologic testing indicates protective levels of antitoxin, since diphtheria infection does not necessarily confer immunity⁽¹⁷⁾.

Table 1 Equine diphtheria antitoxin dosages recommended for various types of diphtheria

Reporting of cases

Report all suspected, probable, or confirmed cases of respiratory diphtheria to local public-health authorities immediately. Additional reporting criteria that may exist in a particular jurisdiction (e.g. for carriers) should be followed. All confirmed cases that meet the current case definition for national notification should be forwarded by provincial and territorial health departments to LCDC as soon as the confirmation is made. Carriers of toxigenic C. diphtheriae and persons harbouring non-toxigenic C. diphtheriae (with or without symptoms) are not notifiable nationally.

The information listed below should be used as a guide for reporting to local health departments. Whenever possible, relevant epidemiologic details (including travel and contact history) should be sought to determine whether the case is indigenous or imported.

Patient details

• Name, age and sex
• Address of residence (and school or other institution, if applicable)
• Hospital where admitted

Laboratory details

• Source of specimen(s) - state if no specimens collected
• Date(s) collected
• Results, if available at time of report
• Name of laboratory that performed the test(s)

Clinical details

• Symptoms
• Date of onset
• Type of antibiotic therapy and starting date
• Antitoxin treatment given

Epidemiologic details

• Diphtheria immunization status
• Travel history of case (within 2 weeks) or close contacts (within 6 months) to an endemic region or during an outbreak period
• List of close contacts (see definition below) - state if there are suspected, probable, or confirmed cases or carriers among contacts

Prevention of secondary cases

Outbreak control measures should be instituted for each case of suspected, probable, or confirmed diphtheria to prevent secondary transmission. However, a decision may be made locally about the intensity of the measures to be taken (e.g. two or more epidemiologically linked cases may require more extensive contact tracing than a single case). Control measures should be undertaken irrespective of whether diphtheria in the index case is indigenous or imported.

Identification and management of close contacts

All persons who have been in contact with a case of diphtheria caused by toxigenic C. diphtheriae in the previous 7 days should be considered at risk. Contacts of cases infected with non-toxigenic C. diphtheriae (or toxigenic and non-toxigenic C. ulcerans) are not considered to be at risk. Contact tracing should be initiated promptly and should begin in the household of the suspected or confirmed case, as the risk of infection is directly related to the closeness and duration of contact and the intensity of exposure. The successful management of contacts depends on close monitoring, prior immunization status and adherence to prophylaxis. The same preventive measures may be taken for contacts of cases and carriers, but the former should be given a higher priority.

Definition of close contacts

Close contacts include

• Household members
• Friends, relatives, and caretakers who regularly visit the home
• Kissing and/or sexual contacts
• Those who share the same room at school or work
• Health-care staff exposed to oropharyngeal secretions of the infected person (staff who have taken appropriate isolation precautions need not be considered contacts).

Follow-up of contacts: Regardless of vaccination status, all close contacts should be kept under daily surveillance for 7 days from the date of last contact with the case and assessed clinically for signs and symptoms of diphtheria, and samples for culturing should be taken from nasal and pharyngeal swabs before antibiotic treatment is started.

Contacts whose occupations involve handling food (especially milk) or involve close contact with unimmunized persons (including children, the elderly, or members of religious groups who do not accept immunizations) should be excluded from their work until bacterial examination proves them not to be carriers.

Antibiotics: Antibiotic prophylaxis should be given to all contacts regardless of vaccination status; a single intramuscular dose of benzathine penicillin G (600,000 units for persons < 6 years of age and 1.2 million units for persons > 6 years of age), or a 7- to 10-day oral course of erythromycin (40 mg/kg daily for children and 1 g/d for adults, in four divided doses) is recommended. For reasons of compliance benzathine penicillin G is preferred for contacts who cannot be kept under surveillance. For contacts proven to be carriers, two follow-up cultures should be obtained at least 24 hours apart and 2 weeks after the completion of therapy. If cultures are positive, an additional 10-day course of erythromycin should be given.

Immunization: Close contacts should be given a dose of a toxoid preparation appropriate to their age unless they are known to have been fully immunized, with the last dose given in the previous 10 years. The remaining doses required to provide full immunization should be given to any contacts who were previously unvaccinated or incompletely vaccinated⁽¹⁷⁾.

If sustained transmission of diphtheria becomes a real threat in a particular community, specific recommendations should be considered for booster immunization of high-risk adults in the community, such as those in older age groups, among whom a higher likelihood of non-protective antitoxin levels has been demonstrated.

There is no acceptable clinical evidence of prophylactic efficacy for antitoxin. The administration of prophylactic antitoxin (with antibiotics as above) should be considered only for the rare, exposed person who cannot be kept under surveillance (5,000 units to 10,000 units intramuscularly)⁽²⁾. If antitoxin is used, it should be preceded by sensitivity testing and desensitization if needed.

Management of carriers

Definition: A carrier is defined as a person who harbours and may disseminate C. diphtheriae but who manifests no upper respiratory tract (pharyngitis or laryngitis) or systemic symptoms. Carriers include those with otitis media, nasal or cutaneous infections and asymptomatic pharyngeal infections due to toxigenic C. diphtheriae.

Antibiotic therapy: Carriers should be given antibiotic prophylaxis regardless of vaccination status; a single intramuscular dose of benzathine penicillin G (600,000 units for persons < 6 years of age and 1.2 million units for persons > 6 years of age), or a 7- to 10-day oral course of erythromycin (40 mg/kg daily for children and 1 g/d for adults, in four divided doses) is recommended. Follow-up cultures should be obtained at least 24 hours apart and 2 weeks after completion of therapy. If cultures are positive, an additional 10-day course of erythromycin should be given.

Antitoxin: Antitoxin has no proven role in the treatment of diphtheria carriers. However, some experts recommend 20,000 units to 40,000 units for cutaneous diphtheria because toxic sequelae have been reported⁽²⁵⁾.

Immunization: Unvaccinated carriers (and those of unknown vaccination status) should receive an immediate dose of a toxoid preparation appropriate for age and should complete the full primary course. Previously vaccinated carriers who have not received a booster dose within 10 years should receive a booster dose of a toxoid preparation appropriate for age.

Isolation: Standard and droplet precautions (see Appendix D) should be observed for hospitalized pharyngeal or nasal carriers of toxigenic strains until two negative cultures have been obtained at least 24 hours apart and 2 weeks after completion of antibiotic therapy.

Standard and contact precautions (see Appendix D) should be observed for hospitalized carriers with cutaneous diphtheria until two negative cultures from skin lesions are obtained at least 2 weeks after completion of antibiotics. All wounds and skin lesions should be vigorously cleaned with soap and water.

Non-hospitalized carriers should be excluded from the workplace or school until two negative cultures are obtained after completion of antibiotics. Contact with other persons in the home should be minimized when appropriate. Individuals who are carriers should be instructed to pay strict attention to personal hygiene by

• covering the nose and mouth with tissue when coughing
• placing all contaminated tissues directly into garbage containers
• washing hands with soap and water every time there is contact with respiratory secretions or infected wounds
• keeping all infected wounds covered.

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