On this page

1. The disease
2. Routine prevention activities
3. Surveillance objective
4. Data management
5. Communications
6. Case definition
7. Laboratory testing
8. Case management
9. Environmental evaluation
10. Contact management
11. Special situations

1. The disease

Infectious agent

Diphtheria is an infection caused primarily by toxin producing Corynebacterium diphtheriae bacteria, a gram-positive bacillus. A lysogenic ß-phage is required for the production of a potent exotoxin that inhibits protein synthesis in mammalian cells and is the major virulence mechanism leading to human disease. Nontoxigenic strains occasionally cause less severe disease. These do not meet the definition of diphtheria.

Corynebacterium ulcerans bacteria can also carry the phage and cause diphtheria. They are predominantly animal pathogens but cause human disease as zoonotic infections.

Reservoir

C. diphtheriae: Humans. The disease has rarely been isolated from horses, cattle and domestic cats.

C. ulcerans: A range of domestic and wild animals

Mode of transmission

C. diphtheriae: Transmission occurs person to person via respiratory droplets or direct contact with respiratory secretions or cutaneous exudate of an infected person. Due to prolonged bacterial shedding, cutaneous diphtheria plays an important role in transmission to susceptible persons, via contact with the wound or contaminated fomites. Transmission from cutaneous lesions can cause respiratory disease in cases and contacts.

C. ulcerans: Transmission of C. ulcerans between humans has never been confirmed. Historically C. ulcerans has been associated with drinking raw or unpasteurised milk products.  It has also been linked to direct contact with domestic and farm animals. In the international literature four reports of detection of asymptomatic C. ulcerans nasopharyngeal carriage among contacts of confirmed cases have raised the possibility of human-to-human transmission, although these cases were also exposed to a common animal source.

Clinical presentation and outcome                                                                          

The disease diphtheria refers to infection with toxigenic strains of C. diphtheriae or C. ulcerans, which are phenotypically indistinguishable. There are two main forms – respiratory and cutaneous.

Non-toxigenic strains of C. diphtheriae can also cause infections in mucous membranes, and invasive infections including septicaemia, endocarditis and septic arthritis.

Respiratory diphtheria

Classic respiratory diphtheria is an upper respiratory tract illness typically associated with a toxin mediated pseudomembrane at the back of the throat and can be associated with severe systemic manifestations. Onset is often gradual, with symptoms of fever, sore throat and weakness. Primary infection most often involves the tonsils and pharynx, but may also involve the larynx, nose, trachea and bronchi. Dysphagia, headache and altered voice occur in fewer than half of patients. Significant neck oedema (“bull neck") and difficulty breathing occur in <10% of patients and are associated with an increased risk of death. Isolated spots of grey or white exudate appear on the pharynx, which extend and coalesce over 24 hours to form a confluent, sharply demarcated pseudomembrane. It progressively thickens, becomes tightly adherent to the underlying tissue, and darkens in colour. This pseudomembrane is caused by liberation of a specific cytotoxin. Dislodging the pseudomembrane, mechanically or as the disease progresses, may cause profuse bleeding, asphyxiation and death.

Systemic manifestations are primarily due to effects of diphtheria toxin. Myocarditis and polyneuropathy are the prominent toxic manifestations. Cardiac effects usually begin about one week after onset of illness and may include dysrhythmias, conduction disturbances and dilated cardiomyopathy. Neuropathy typically begins weeks to months after onset of diphtheria in 20%–25% of untreated cases and is the cause of 15% of deaths. Neuropathy can present as cranial nerve paresis, respiratory and abdominal muscle weakness, quadriparesis or quadriplegia, peripheral sensory disturbances, and a variety of autonomic disturbances.

The case fatality rate of classic respiratory diphtheria is 5-10%, even with appropriate treatment.

Cutaneous diphtheria and other sites of infection

Cutaneous diphtheria usually appears on exposed limbs, particularly the legs and presents either as:

• secondary infection of existing skin lesions commonly associated with Staphylococcus aureus and group A streptococci growth or
• primary punched out ulcers with well-demarcated edges and a cover of bluish-grey necrotic slough or membrane.

Cutaneous diphtheria is only rarely associated with systemic toxic effects in the individual.

Incubation period

Median incubation period from exposure to onset of symptoms is 1.4 days. The range is generally 2 to 5 days but may be longer, with duration up to 10 days reported. Chronic carriage of toxigenic strains can occur without clinical disease.

Infectious period                                                                         

C. diphtheriae: The period of communicability is variable. Untreated cases are colonised for 18.5 days on average and 95% of cases clear C. diphtheriae within 48 days. Asymptomatic cases cause 76% fewer secondary cases than symptomatic cases and appropriate vaccination with diphtheria toxoid vaccine reduces transmission by 60%. Effective antimicrobial therapy reduces communicability by up to 2 weeks and terminates bacterial shedding from respiratory colonisation on average within 5.2 days.

For the purposes of contact tracing, follow up, and recommendations around isolation and restriction, the symptoms of the case, closeness, and duration of contact are important considerations in the likelihood of spread of the disease. Prolonged contact is usually required for spread, particularly from an asymptomatic person.

As asymptomatic carriage and transmission can occur prior to onset of symptoms, consider the infectious period as:

• 7 days prior to onset of respiratory symptoms or
• 7 days prior to positive nasopharyngeal and/or throat swab (if asymptomatic) or
• The date of skin infection began

whichever is earlier.

UNTIL

• Demonstrated clearance of infection by nasopharyngeal and throat swabs, for respiratory diphtheria or
• 72 hours of appropriate antibiotics have been received for cutaneous diphtheria AND wound can be appropriately covered (see 'isolation and restriction').

C. ulcerans: Transmission of C. ulcerans between humans has never been confirmed. Asymptomatic, nasopharyngeal carriage of toxigenic, genetically related strains in close contacts of cases has been reported, indicating this route of transmission is theoretically possible.

Persons at increased risk of disease

• Unvaccinated or under-vaccinated people
• People living in crowded or unsanitary conditions
• Travellers to countries with higher rates of diphtheria or lower vaccination coverage: parts of the South Pacific, South and South-East Asia, the Middle East, Eastern Europe, South and Central America.

Cutaneous diphtheria is more common in tropical countries and is associated with contact with animals.

Immunity

Infection can occur in vaccinated as well as unvaccinated people. Lifelong immunity is generally (but not always) acquired following disease or subclinical infection. Vaccination reduces the frequency and severity of disease and provides prolonged, but not lifelong, immunity. Post-vaccination antibody levels wane by 0.6% per year since vaccination. Immunity is antibody modulated and primarily against the toxin rather than the bacteria; therefore, vaccinated persons can still harbour the organism.

Infants born to immune mothers have passive protection, which is usually lost before six months of age. Serosurveys in Australia indicate decreasing levels of adult immunity.

Disease occurrence and public health significance                           

Diphtheria was a common cause of death among children in the pre-vaccine era.  Diphtheria has been well controlled in Australia since the introduction and widespread use of the diphtheria-containing vaccine.

In Australia, most cases of diphtheria are reported from Queensland. From 1 January 2011 to 31 December 2021, Queensland recorded six cases of respiratory diphtheria (0.01 per 100,000 population per year) and 39 cases of cutaneous diphtheria (0.07 per 100,000 population per year). Cases had largely been observed in overseas travellers and their contacts. Two unvaccinated adults died from respiratory diphtheria in 2011 and 2018. In 2022, notifications of locally acquired diphtheria cases increased in Queensland, with four (0.1 per 100,000 population) respiratory cases and twenty (0.4 per 100,000 population) cutaneous cases, related to an outbreak on in Northern Queensland.

In NSW there was one case of locally acquired respiratory diphtheria and three cases of overseas acquired cutaneous diphtheria in 2018 (no notifications were received between 2000-2017). Cases have continued in NSW, with four cases reported in 2022, three of which were locally acquired.

The public health management of these infections can be complex, including managing the emergence of antibiotic resistance.

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2. Routine prevention activities

Apart from direct case and contact management of diphtheria, the following activities are routine prevention activities at the population level.

Vaccination

The most effective preventive measure is widespread vaccination with diphtheria-containing vaccines, both routine vaccination of infants and children and routine booster vaccination in adolescents and adults. Special efforts should be made to ensure that people at higher risk of exposure, e.g., healthcare workers, are fully vaccinated. Vaccine-induced immunity wanes over time and, without booster immunisations, the proportion of the population who are susceptible increases.

Increased awareness

Amongst general practitioners and clinicians, it is important to promote ongoing education on diphtheria that outlines clinical features, diagnosis, treatment and timely referral to public health units (PHU).

Communicating to the public when cases occur in specific communities or locations likely improves public awareness and recognition of disease.

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3. Surveillance objective

• To identify cases and prevent further transmission
• To monitor the epidemiology to inform improved prevention strategies.

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4. Data management

Within 1 working day of notification the PHU should enter probable and confirmed cases onto NCIMS.

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5. Communications

The laboratory or clinician should notify the PHU of any clinically suspected case, culture positive diphtheria case (prior to obtaining toxin testing result) or confirmed case. The clinician should notify the PHU of the case's age, sex, date of onset, clinical status, laboratory findings and vaccination history. PHUs should notify CDB immediately of a probable or confirmed case and or any death from diphtheria.

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6. Case definition

Both confirmed cases and probable cases should be notified.

Confirmed case

A confirmed case requires laboratory definitive evidence and clinical evidence (for a confirmed case).

Laboratory definitive evidence

Isolation of toxigenic* Corynebacterium diphtheriae or toxigenic* C. ulcerans from site of clinical evidence.

*As indicated by detection of toxin gene by nucleic acid testing

Clinical evidence (for a confirmed case)

1. Upper respiratory tract infection or
2. Skin lesion

Probable case

A probable case requires:

1. laboratory suggestive evidence and clinical evidence (for a probable case) or
2. clinical evidence (for a probable case) and epidemiological evidence.

Laboratory suggestive evidence

Isolation of C. diphtheriae or C. ulcerans from a respiratory tract specimen (toxin production unknown).

Clinical evidence (for a probable case)

Upper respiratory tract infection with an adherent membrane of the nose, pharynx, tonsils, or larynx.

Epidemiological evidence

An epidemiological link is established when there is contact between two people involving a plausible mode of transmission at a time when:

1. one of them is likely to be infectious (usually 2 weeks or less and seldom more than 4 weeks after onset of symptoms) and
2. the other has an illness which starts approximately 2-5 days after this contact and
3. at least one case in the chain of epidemiologically linked cases (which may involve many cases) is laboratory confirmed.

Possible case

A possible case requires:

A skin lesion and either

1. isolation of C. diphtheriae or C. ulcerans from a wound swab (toxin production unknown) or
2. epidemiological evidence.

This should be recorded on NCIMS as a “possible case" until either confirmed or excluded.

Notification procedure

Diphtheria is to notified by:

• Attending clinicians on clinical diagnosis (ideal reporting by telephone within 1 hour of diagnosis)
• Laboratories on microbiological confirmation (ideal reporting by telephone within 1 hour of diagnosis)

Confirmed, probable and possible cases should be entered onto the jurisdictional notifiable diseases database.

Clinical notification (for possible cases)

Cases may be suspected as described above and laboratory confirmation is awaited. Possible cases should be notified to the local PHU.

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7. Laboratory testing

Corynebacterium species are commensal organisms of the skin and throat. They generally do not cause disease. C. diphtheriae or C. ulcerans may not be identified from a skin, nasopharyngeal or throat swab unless there is a specific request noting clinical suspicion conveyed to the laboratory via the request form e.g., “culture for suspected diphtheria". Swabs should be collected using Amies transport medium swabs.

Laboratory confirmation is typically by a combination of culture, bacterial isolation and preliminary identification of C. diphtheriae or C. ulcerans in a clinical laboratory followed by confirmation and toxigenicity testing at a reference laboratory.

Culture

In NSW, most laboratories will identify C. diphtheriae or C. ulcerans by microbiological culture on standard blood agar or preferably on tellurite-containing media, such as Hoyle's agar. Diphtheria culture should be specified on the request form to ensure the appropriate selective media is used. Some laboratories do not routinely carry appropriate media and will send specimens on for culture to an appropriate laboratory. PHUs should anticipate a delay in result and work with the relevant laboratories to expedite transport as required.

Nucleic acid testing (NAT) for tox gene

In NSW, isolates from clinical specimens identified as C. diphtheriae or C. ulcerans are routinely referred to the Centre for Infectious Diseases and Microbiology Laboratory Services (CIMDLS), Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital for diphtheria toxin testing by NAT. This test is designed to detect the phage encoded diphtheria toxin gene, “tox". Detection of the tox gene indicates that the strain is toxin-gene positive not necessarily toxigenic.

For the practical response purposes of this guideline, and for consistency with the national case definition, detection of tox gene by NAT is evidence of and equivalent to isolation of toxigenic C. diphtheriae or toxigenic C. ulcerans.

Diphtheria toxin testing at ICPMR is done during normal business hours Monday to Friday, with specimens labelled urgent being prioritised, with an approximate turnaround time of 3 days from receipt of C. diphtheriae or C. ulcerans isolate to NAT result. Receipt of the primary clinical specimen rather than an isolate at ICPMR will increase turnaround times. Urgent after-hours testing should be requested by senior PHU staff directly (e.g., PHU director, staff specialist, or appropriate delegate) to the clinical microbiologist on-call via the Westmead Hospital switchboard (02 8890 5555) if the result will have clinical or public health implications. 

Strain differentiation

Whole genome sequencing of isolates or multi-locus sequence typing (MLST) can be performed for surveillance purposes or investigation of epidemiological links. The clinical microbiologist on-call via Westmead Hospital switchboard can facilitate this if required.

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8. Case management

Response times

On the same day of notification of a confirmed case, begin follow-up investigation.

Investigation of cases pending toxin result (probable and possible)

On the same day of notification, begin follow up investigation for a probable case. The treating clinician should have an urgent direct conversation with an infectious disease specialist to assess the likelihood of diphtheria, if necessary facilitated by the PHU. If local infectious disease services are not available, the NSW specialist service for High Consequence Infectious Disease on-call clinician should be contacted for advice. 

The below steps outlined in 'case investigation', including preliminary contact tracing should be considered in:

• probable cases
• clinically suspicious cases - this may be the circumstance where diphtheria is a possibility, but the person does not meet the current case definitions e.g., a person with a known epidemiological link and acute respiratory symptoms without a pseudomembrane
• situations with public health implications (e.g., homelessness, large potential number of contacts, large exposure event, priority populations).

The below steps should be considered, particularly if there is likely to be significant delays in obtaining definitive testing results. Apply appropriate transmission-based precautions while awaiting toxin test results (see 'isolation and restriction' below). If speaking with the case, urge household members ensure they are up to date with their vaccinations.

On the same day of notification, possible cases should have a preliminary risk assessment conducted by the PHU (director or appropriately senior staff) in conjunction with specialist infectious disease advice. This risk assessment should guide the extent of initial investigation whilst awaiting toxin testing results. If there are minimal potential public health impacts (e.g., wound can be covered, low number of potential contacts), it may be appropriate to obtain clinical history, including vaccination status, and ensure the isolate is sent initially only for toxin testing at ICPMR and the appropriate isolation and restriction protocols are in place (see 'isolation and restriction; Cutaneous Diphtheria' below). Nasopharyngeal and throat swabs of the possible case or contact tracing of the possible case could be delayed until toxin testing results are available.

Response procedure

Case investigation

Classical respiratory diphtheria is a medical emergency due to the possible need for airway protection. Urgent referral for medical assessment is warranted with consideration of diphtheria antitoxin.

The response to a notification will usually be carried out in collaboration with the case's medical team. Ensure that action has been taken to:

• discuss with the treating doctor the need to interview the case or the relevant caregiver in order to provide information and seek a contact history.
• establish what the case or the relevant caregiver has already been told about the diagnosis before beginning the interview.
• obtain clinical history including any history of travel and vaccination status.
• ensure nasopharyngeal, throat and wound swabs have been taken (including nasopharyngeal and throat swabs for confirmed cutaneous cases). Amies transport medium swabs (for bacterial culture) should be used. Specify “culture for suspected diphtheria" on request form.
• if C. diphtheriae or C. ulcerans is isolated, ensure the isolate is sent to ICPMR for toxin testing. The PHU should assess how urgently this result is needed, based on the risk to contacts and ability to restrict and isolate probable and possible cases, or any other relevant factors, as toxin testing is conducted during business hours Monday to Friday. Urgent testing requested out of hours should be discussed by senior PHU staff directly with the clinical microbiologist on call at ICPMR.
• if the initial nasopharyngeal and/or throat swabs of a case with confirmed cutaneous diphtheria are positive (indicating nasopharyngeal carriage), then manage as per a confirmed respiratory case.
• apply isolation and restriction measures.
• carry out contact tracing.
• inform CDB and the adjacent PHUs (if relevant) of the notification.
• Discuss a media release with CDB to help alert community members of the risk and promote vaccination.

If a non-toxigenic strain of C. diphtheria or C. ulcerans is identified, public health interventions can cease.

Exposure investigation

Investigate the possible source of exposure; contact with a confirmed, probable, or possible case and/or travel history.

Due to the zoonotic nature of C. ulcerans infection, it is important to identify any potential animal source. Enquire about consumption of raw milk and contact with animals, including livestock and domestic animals. Where the case's infection has been acquired in Australia and the case has had contact with animals during the incubation period, call the One Health Branch in Health Protection NSW to discuss screening of potential animal sources.

Case treatment

Antibiotics

The treating clinician with specialist infectious disease advice as required will determine appropriate therapy for confirmed, probable and possible cases of diphtheria. 

Choice of antibiotic therapy should consider the likelihood of penicillin resistance, and the presence of other bacteria (especially in wounds).

Antibiotics should be given immediately but AFTER appropriate swabs are taken wherever possible.

Generally, treatment should continue for 14 days. Elimination of respiratory diphtheria should be confirmed by nasopharyngeal swab culture (see “isolation and restriction"). If microbiological clearance by negative nasopharyngeal and throat culture is not achieved, an additional 10-day course of antibiotics is recommended.

Diphtheria antitoxin (DAT)

DAT is considered the mainstay of treatment for respiratory diphtheria. Antibiotics are required to eradicate the organism, stop further toxin production and help prevent transmission. DAT is not usually required for asymptomatic carriage, cutaneous infection or prophylaxis. Post infection administration of DAT reduces mortality by 76%.

NSW has access to a limited supply of DAT. DAT can be requested after consultation with the on-call physician for the NSW specialist service for High Consequence Infectious Disease (HCID), located at Westmead Hospital. The treating clinician of any suspected, probable, or confirmed case should liaise with the HCID on-call physician to discuss clinical indications of DAT use and recommended dosage. The HCID on-call physician will use the HCID Standard Operating Procedure and DAT protocol to coordinate the transfer of DAT when indicated.

Ask the treating clinician or HCID on-call physician to provide an update of any patient requiring DAT and if so the PHU should notify CD on-call. If the local PHU is notified in the first instance of any case that potentially requires DAT, the PHU should direct the treating clinician to the HCID on-call physician.

The NSW specialist service for HCID on-call physician can be contacted via 1800 HCID 00 (1800 424 300).

When indicated, DAT should be given promptly. DAT is most effective against circulating diphtheria toxin and less effective once the toxin is bound to tissue, meaning DAT does not reverse symptoms caused by bound toxin. Rather, it limits disease progression making early administration critical. Mortality is most significantly reduced if given within 24 hours, with reduced efficacy if administered after this. Clinicians should not await laboratory confirmation of toxin testing to administer DAT if there is strong clinical suspicion for diphtheria and should discuss with the HCID on-call physician.

DAT is only to be used in a hospital setting with oversight by the infectious diseases or treating physician. DAT is derived from equine serum. There is the potential risk of a hypersensitivity reaction. Sensitivity testing should be considered before giving antitoxin and should be carried out by the treating team in conjunction with the HCID on-call physician.

Immunisation

Ascertain the case's diphtheria vaccination status.

Cases of both cutaneous and respiratory diphtheria should be vaccinated in the convalescent phase of their disease as clinical infection may not induce adequate immunity. Children and adult cases who have completed their primary course of diphtheria-containing vaccines should receive one booster dose of a diphtheria-containing vaccine if it is more than 12 months since their last dose. Unvaccinated or incompletely vaccinated cases should commence a primary or catch-up course of diphtheria vaccination as per the Australian Immunisation Handbook. If a case received DAT, diphtheria vaccination should be delayed for four weeks.

Education

The case should be advised of the nature of the infection and its mode of transmission. Provide the NSW Health factsheet to cases and contacts.

Isolation and restriction

Respiratory diphtheria

Cases with respiratory diphtheria should be managed with standard, contact and droplet precautions.  Further detail can be found in the Infection Prevention and Control Practice handbook.

Droplet and contact precautions should remain until two negative nasopharyngeal and throat cultures taken at least 24 hours apart and more than 24 hours after the cessation of appropriate antimicrobial therapy are obtained.

Confirmed and probably cases of respiratory diphtheria should be excluded from work, school or childcare until clearance nasopharyngeal and throat cultures are obtained.

Contact and droplet precautions can be ceased if probable respiratory cases are excluded with negative diphtheria toxin testing result.

Cutaneous diphtheria

Cases with confirmed or possible cutaneous diphtheria should be managed with standard and contact precautions. Wounds should be covered. In addition, droplet precautions should be used until:

• The initial nasopharyngeal and throat swabs are culture negative; or 
• 72 hours of appropriate antimicrobial therapy has been completed, whichever is shorter.

Contact precautions should continue until:

• All wounds are clinically improving and can be covered by an occlusive waterproof dressing or have healed; and
• 72 hours of appropriate antimicrobial therapy has been completed.

Contact and droplet precautions can be ceased if possible cutaneous cases are excluded with negative diphtheria toxin testing result.

Confirmed, and possible cases of cutaneous diphtheria should be excluded from group settings including e.g., childcare, school, aged care, or visiting a healthcare facility until the above criteria for precautions and antibiotics are met or the possible case is excluded (non-toxigenic test result obtained).

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9. Environmental evaluation

If there is a possible local animal source for a C. ulcerans case, the PHU should contact the One Health Branch.

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10. Contact management

Identification of contacts

Contacts are tested and treated to avert incubating disease, prevent further spread and eliminate asymptomatic carriage.

Contact tracing is required for confirmed cases of toxigenic C. diphtheria or C. ulcerans.

Initiate contact tracing (focusing on education and vaccination) for high risk contacts of probable cases (and consider possible cases) where there is high clinical suspicion of diphtheria or likely to be a delay in receiving results of toxin testing.

Contact definition

Contacts are individuals who were in contact with the case during their infectious period without appropriate protection.

Contacts can be classified as high, medium, or low risk according to the level of exposure to a case, see Table 1. Further examples of high, medium and low risk contacts can be found in Appendix A.

Table 1: Contacts classification based on exposure risk

11. Special situations

Outbreaks

An outbreak is defined as two or more cases who share a plausible epidemiological link e.g., clustered in time and place. An outbreak management team may need to be established. CDB and all relevant public health units should be notified and involved.  Key issues include nomination of roles to ensure efficient reporting and communication of issues within the response framework. Early communication of risk to affected institutions is essential.

Communication to external stakeholders and the media will involve discussion of often complex medical concepts e.g., 'carriage' of the organism in vaccinated populations. It is imperative that early discussion take place with agreement on the key public health messages. In the event of a local outbreak, the local PHU should lead the media and communication response. 

An outbreak should prompt an urgent review of vaccination status in that group and consideration of urgent catch-up immunisation or a pop-up vaccination clinic as required.

An expert advisory group may be called at the discretion of the public health unit managing the case(s) or CDB.  Particularly, an expert group may be appropriate for situations that are extraneous to these guidelines.

Public health response for toxigenic diphtheria cases in Aboriginal communities

Early consultation and partnership with community leaders and representatives is important when managing diphtheria cases and contacts in an Aboriginal community. If an outbreak control team is convened, include appropriate Aboriginal stakeholders. This member could be the health service Aboriginal Health director or delegate, Aboriginal Community Controlled Health Service member or council nominee.

In addition to case and contact investigation and management as outlined above, consider the following public health actions in partnership with the Aboriginal community:

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Appendix A: Contact risk classification and management

Settings based contact risk category matrix

*Aircraft: There is usually no requirement to contact trace those in adjacent seats in the following circumstances:

• Someone with appropriately covered cutaneous diphtheria and negative initial nasopharyngeal and throat swabs travelled on a long-distance flight.

Management

High Risk Contact: Likely/definite exposure to respiratory droplets, or direct contact with respiratory secretions or wound exudate (e.g., prolonged, close exposure to uncovered wound or respiratory droplets without PPE)

• Provide information and advice to monitor for symptoms for at least 7 days after contact
• Swab^# nasopharynx and throat, and any skin lesions
• Provide antibiotics
• Avoid contact with vulnerable populations (infants aged ≤6 months, sick, elderly and those requiring dependent care, and immunosuppressed individuals) until swabs returned negative result or 72 hours of antibiotics completed, whichever is shorter. In the household this requires avoidance and work situations this requires exclusion from the workplace.
• Recommend a booster dose of vaccine if greater than 12 months since last dose received
• Primary or catch-up course of vaccination if unvaccinated or incomplete.

Medium Risk Contact: Uncertain exposure requiring further risk assessment

At a minimum:

• Provide information and advice to monitor for symptoms for at least 7 days after contact
• Consider swab^# of nasopharynx and throat, and any skin lesions
• Consider antibiotics
• Recommend a booster dose of vaccine if greater than 12 months since last dose received
• Primary or catch-up course of vaccination if unvaccinated or incomplete.

Additional measures will depend on consideration of risk factors.

Low risk Contact: Very unlikely/no exposure to respiratory droplets, nor direct contact with respiratory secretions or wound (e.g., appropriate PPE, distant contact only, covered wound).

Where appropriate and feasible:

• Provide information about symptoms
• Recommend opportunistic booster dose of vaccine if >10 years since last dose
• Primary or catch-up course of vaccination if unvaccinated or incompletely vaccinated.

Additional measures will depend on consideration of risk factors.

^# Swabs should ideally be combined nasopharyngeal and throat swabs, however, in institutional settings where there may be requirement to swab large numbers of contacts, combined nasal/deep nasal and throat swabs may be substituted to improve timeliness.

References

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2. Goldman L, Schafer AI. Goldman-Cecil Medicine. 26 ed: Philadelphia, PA: Elsevier; 2020.

3. Horn KJ, Jaberi Vivar AC, Arenas V, Andani S, Janoff EN, Clark SE. Corynebacterium species inhibit streptococcus pneumoniae colonization and infection of the mouse airway. Front Microbiology. 2022;12.

4. Mandell GJ, Bennett JE, Dolin RB. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. Philadelphia, PA: Elsevier; 2020.

5. Truelove SA, Keegan LT, Moss WJ, Chaisson LH, Macher, E, Azman AS, et al. Clinical and epidemiological aspects of diphtheria: A systematic review and pooled analysis. Clinical Infectious Diseases. 2020;71:89-97.

6. Wagner KS, White JM, Crowcroft NS, De Martin S, Mann, G, Efstratiou A. Diphtheria in the United Kingdom, 1986-2008: The increasing role of corynebacterium ulcerans. Epidemiology and Infection. 2010;138(11):1519-30.

7. NHMRC. Australian Guidelines for the Prevention and Control of Infection in Healthcare (2019). NHMRC. Canberra: Commonwealth of Australia; 2019.

8. Centers for Disease Control and Prevention. Expanded access Investigational New Drug (IND) application protocol: Use of diphtheria antitoxin (DAT) for possible diphtheria cases. Centers for Disease Control and Prevention. 2022.

9. United Kingdom Health Security Agency. Public health control and management

of diphtheria in England: 2022 guidelines. London: UK Health Security Agency. (https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1117027/diphtheria-guidelines-2022_v17_111122.pdf), 2022.