Diphtheria

Queensland Health Guidelines for Public Health Units

• Infectious Agent
• Case definitions and notification criteria
• Notification Procedure
• Objectives of surveillance
• Public Health Significance and Occurrence
• Clinical Features
• Reservoir
• Mode of Transmission
• Incubation Period
• Period of Communicability
• Susceptibility
• Management
• Preventive Measures
• Appendix A: Public health response for toxigenic diphtheria cases in priority communities
• Appendix B: DAT treatment for cases of respiratory diphtheria
• Appendix C: Contact risk classification and management
• Appendix D: Antibiotic prophylaxis for contacts and treatment for carriers (asymptomatic cases) of diphtheria
• References
• Revision History

Infectious Agent

Diphtheria is a disease caused primarily by toxigenic Corynebacterium diphtheriae bacteria, a gram-positive bacillus. Toxigenicity occurs when the bacillus becomes infected with a specific virus (corynebacteriophage) which carries the gene for the toxin (tox gene).  The potent exotoxin is the major virulence mechanism leading to human disease. ^1,2

Nontoxigenic strains occasionally cause disease of varying severity, particularly in vulnerable populations.¹ These do not meet the definition of diphtheria.

Corynebacterium ulcerans and, rarely, Corynebacterium pseudotuberculosis bacteria can also carry the phage and cause toxigenic diphtheria.^1,2  They are predominantly animal pathogens but cause human disease as zoonotic infections.

Case definitions and notification criteria

Both confirmed cases and probable cases should be notified.

Confirmed case

Confirmed case requires laboratory definitive evidence and clinical evidence.

Laboratory definitive evidence

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

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

Clinical evidence

Clinical evidence requires:

• Upper respiratory tract infection

OR

• Skin lesion

Probable case

A probable case requires:

• laboratory suggestive evidence AND clinical evidence

OR

• clinical evidence AND epidemiological evidence.

Laboratory suggestive evidence

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

Clinical evidence

Upper respiratory tract infection with an adherent pseudomembrane 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:

• one of them is likely to be infectious (usually 2 weeks or less and seldom more than 4 weeks after onset of symptoms)

AND

• the other has an illness which starts approximately 2-5 days after this contact

AND

• at least one case in the chain of epidemiologically linked cases (which may involve many cases) is laboratory confirmed.

See Appendix A: Queensland public health response for toxigenic diphtheria cases in priority communities, as outbreaks may not follow typical epidemiological patterns.

Notification Procedure

Clinical notification – suspected cases

Cases may be suspected where there is clinical and epidemiological evidence and laboratory confirmation is awaited.

Attending Medical Practitioners/Medical Superintendents (or delegates) are to notify urgently on clinical suspicion of respiratory diphtheria by usual means to the local public health unit.

Pathology laboratories

To notify local public health unit urgently on confirmation of diagnosis by usual means.

For further information, access Guidelines for Laboratories.

Laboratory aspects

Corynebacterium species are organisms of the skin and throat, which uncommonly cause disease.³ C. diphtheriae or C. ulcerans may not be identified from a skin or throat swab unless there is a specific request noting clinical suspicion conveyed to the laboratory via the request form, e.g., “suspected diphtheria case”.

In Queensland, isolates from clinical specimens identified as C. diphtheriae or C. ulcerans are routinely referred to Queensland Health Forensic and Scientific Services (FSS) for diphtheria toxin testing by nucleic acid testing (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.

Whole genome sequencing of isolates and selected isolates for multi-locus sequence typing (MLST) level is performed for surveillance purposes.

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Objectives of surveillance

• To identify cases, disease clusters and state trends to inform appropriate public health management and preventative action.
• To meet national reporting requirements.

Public health significance and occurrence

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 toxoid vaccine. From 1 January 2011 to 31 December 2021, the Queensland Notifiable Condition System 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. There have been 3 deaths from diphtheria in unvaccinated adults, 2 cases in 2011 and 1 in 2018.

In 2022, the numbers of notifications of locally acquired diphtheria cases have increased in Queensland, with 4 (0.1 per 100,000 population) respiratory cases and 20 (0.4 per 100,000 population) cutaneous cases. Cases were predominantly reported in North Queensland Indigenous communities with genomic clustering demonstrated.⁴

Persons of any age who are unvaccinated or under-vaccinated are at highest risk of disease, particularly if it is more than 10 years since the last dose.² There is a particular risk for persons travelling to regions with vaccine program disruptions and where diphtheria remains more common, including Asia, South Pacific, the Middle East and Eastern European countries.² Vaccine-induced immunity wanes over time and without booster immunisations, the proportion of the population who are susceptible increases.¹

During outbreaks, the baseline vaccination status of the community should be considered in the public health response, refer to: Appendix A: Queensland public health response for toxigenic diphtheria cases in priority communities.

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Clinical Features

Diphtheria refers to the toxin-mediated illness and there are two main forms – respiratory and cutaneous. It can be caused by toxigenic strains of C. diphtheriae, C. ulcerans or C.pseudotuberculosis. The toxin causes local tissue necrosis and is associated with the development of a pseudomembrane at the back of the throat in respiratory disease and may cause severe systemic manifestations.²

Cases of asymptomatic or mild respiratory infection (without a pseudomembrane) and non-healing ulcers caused by toxigenic strains of C. diphtheriae and C. ulcerans will also be detected through enhanced surveillance. This is more common in vaccinated persons as the vaccine is protective against the effects of the toxin.

Non-toxigenic strains of C. diphtheriae and C. ulcerans can cause infections in mucous membranes, and invasive infections including septicaemia, endocarditis and septic arthritis.²

Respiratory diphtheria

Onset is often gradual, with symptoms of low-grade fever, sore throat and malaise.^1,5 Primary infection most often involves the tonsils and pharynx, but may also involve the larynx, nose, trachea and bronchi. Three days post-onset, isolated white or grey spots appear which extend and coalesce to form a confluent, sharply demarcated pseudomembrane.⁵ It progressively thickens, becomes tightly adherent to the underlying tissue, and darkens in colour.¹ Dislodging the pseudomembrane, mechanically or as the disease progresses, may cause profuse bleeding, asphyxiation and death.¹

Systemic manifestations are due primarily to toxic effects of diphtheria toxin. Cardiac effects, such as dysrhythmias, conduction disturbances and dilated cardiomyopathy, usually present 7-14 days after the onset of respiratory symptoms in 10-25% of cases.⁶ Neuropathy typically begins weeks to months after onset of diphtheria in 20%–25% of untreated cases and is the cause of 15% of deaths.⁶ The case fatality rate of classic respiratory diphtheria is 5-10%, even with appropriate treatment.²

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 grey-white necrotic slough or membrane.²

Cutaneous diphtheria is only rarely associated with systemic toxic effects but can induce high antibody levels as a natural immunising event.²

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Reservoir

C. diphtheriae: Humans, less commonly horses, cattle and domestic cats.⁵

Humans serve as the source of infection, particularly persistent cutaneous cases.⁵ This can include contaminated fomites, particularly in vulnerable communities and settings.^1,5

C. ulcerans: A range of domestic and wild animals.⁷

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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.¹ 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.⁵

C. ulcerans:  Historically has been associated with drinking raw or unpasteurised milk products and is linked to direct contact with domestic and farm animals. Transmission of C. ulcerans between humans has never been confirmed.⁷

Incubation Period

The national surveillance case definition (last reviewed 2004) assumes an incubation period is 2-5 days.⁸ However, more recent evidence suggests it is shorter, with a median time to symptom onset of 1.4 days and mean of 1.9 days.⁶

Period of Communicability

C. diphtheriae: The period of communicability is variable. Untreated cases are colonised for 18.5 days on average and 95% of cases clear C. diphtheria within 48 days. Asymptomatic cases cause 76% fewer 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.⁶

Case symptoms, and closeness and duration of contact are important considerations when assessing risk of spread of disease during contact tracing.

Consider the infectious period as:

• 7 days prior to onset of respiratory symptoms

OR

• 7 days prior to throat swab (if asymptomatic)

OR

• Date of onset of skin infection

UNTIL

• Precautions have been implemented (mask, wound covered)

OR

• Demonstrated absence / clearance of infection.

C. ulcerans: Transmission of C. ulcerans between humans has never been confirmed.

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Susceptibility

Diphtheria toxoid vaccination does not prevent infection or transmission; however, adequate immunisation is 97% effective in preventing toxigenic disease.⁵ There is no clearly defined level of antitoxin demonstrated to provide complete protection. Levels between 0.01 IU/mL and 0.09 IU/mL are regarded as providing basic immunity, while levels of > 0.1 IU/mL may be needed for full protection.⁵ In individuals with significant toxigenic disease and a history of diphtheria vaccination, consider checking antitoxin antibody levels to assess immunity status. Infants born to immune mothers have passive protection, which is usually lost before six months of age. Post-vaccination antibody levels wane by 0.6% per year since vaccination.⁶

Early administration of antitoxin can prevent complications and death from toxigenic disease.¹

Management

Cases

Classical respiratory diphtheria is a medical emergency for airway protection (while using PPE), urgent referral and consideration of DAT. Post-infection administration of Diphtheria antitoxin (DAT) reduces mortality by 76%.⁶ Refer to Appendix B: DAT treatment for cases of respiratory diphtheria.

Investigation of cases pending toxin result

Ensure isolates have been referred for toxin gene testing. Notify laboratory if urgent result required.

Preliminary contact tracing may be considered where pre-test probability is high, particularly if there are likely to be significant delays in obtaining definitive testing results. Apply appropriate transmission-based precautions while awaiting investigation results, e.g., apply mask for respiratory symptoms and cover wounds. Recommend that household contacts of the case are up to date with their diphtheria vaccinations, as per current recommendation.

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

Investigation of probable and confirmed cases

• Obtain clinical history including any history of travel and vaccination status.
• For confirmed cutaneous cases, ensure nasopharyngeal and throat swabs are taken (specify suspected diphtheria on request form).
• Consider taking a sample for antitoxin level testing prior to administration of DAT if vaccinations are up to date.

Restriction and isolation

Cases with respiratory diphtheria should be managed with standard, contact and droplet precautions.¹ The addition of droplet precautions is substantiated in the evidence base, though it is acknowledged that the Australian Guidelines for the Prevention and Control of Infection in Healthcare, recommend standard and contact precautions for cutaneous and pharyngeal diphtheria.⁹

Droplet and contact precautions should remain until 2 negative cultures from nose and throat swabs are obtained. Cultures must be obtained no sooner than 24 hours after the cessation of appropriate antimicrobial therapy and must be taken 24 hours apart.⁵

Confirmed and probable cases of respiratory diphtheria should be excluded from work, school, or childcare until two negative cultures from nose and throat swabs are obtained.

Cases with cutaneous diphtheria should be managed with standard and contact precautions.⁹ Wounds should be covered. In addition, droplet precautions should be used:

• until nasopharyngeal and throat swabs are culture negative*

OR

• 5 days of appropriate antimicrobial therapy has been completed, whichever is shorter.
  * If nasopharyngeal and/or throat swabs are positive, then manage as respiratory diphtheria.

Exclude from work, school, and childcare until:

• all wounds are clinically improving and can be covered by an occlusive waterproof dressing or have healed

AND

• 5 days of appropriate antimicrobial therapy has been completed OR until nasopharyngeal and throat swabs are culture negative*, whichever is shorter.

For further information about standard, contact and droplet precautions, please see the Australian Guidelines for the Prevention and Control of Infection in Healthcare (2019), available from: Australian Guidelines for the Prevention and Control of Infection in Healthcare (2019).

Antibiotics

Antibiotics are required to eradicate the organism, stop further toxin production, and help prevent transmission. Antibiotics should be given immediately AFTER appropriate nose/throat and wound swabs are taken wherever possible.

Choice of antibiotic therapy should consider available susceptibility testing and the likelihood of penicillin resistance. For respiratory diphtheria, seek specialist infectious diseases physician or clinical microbiologist advice and refer to eTG: Topic | Therapeutic Guidelines (tg.org.au)

If microbiological clearance is not achieved, an additional 10-day course of antibiotics may be recommended based on sensitivity profile.

Antitoxin

While antibiotics are necessary, diphtheria antitoxin (DAT) is considered the mainstay of preventing toxin related complications of respiratory disease.¹

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. Details outlining the use and access of DAT are in Appendix B: DAT treatment for cases of respiratory diphtheria. DAT is not usually required for cutaneous infection or mild respiratory disease. DAT is only to be used in a hospital setting with oversight by the infectious diseases physician.

Vaccination

Ascertain diphtheria vaccination status, referring to records if available. Patients should be vaccinated (with the age-appropriate formulation) in the convalescent phase of their disease as clinical infection may not induce adequate immunity.² Children and adults who have completed their primary course of diphtheria-containing vaccines should receive one booster dose of a diphtheria-containing vaccine. Unvaccinated or incompletely vaccinated cases should commence a primary or catch-up course of diphtheria vaccination. If a case received DAT, diphtheria vaccination should be delayed for four weeks. Refer to the current edition of Diphtheria | The Australian Immunisation Handbook for vaccination details.

Counselling

The case should be advised of the nature of the infection and its mode of transmission.

Communications – Respiratory Diphtheria

Relevant public health unit to inform the Communicable Diseases Branch and adjacent public health units of the notification.

Discuss the possibility of a media release by the co-ordinating public health unit.

If proceeding, communication to 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.

C.ulcerans: Investigation and management of cases of respiratory infection caused by toxigenic C. ulcerans is the same as for toxigenic C. diphtheriae infections.  Ensure empiric antibiotic therapy is consistent with the susceptibility profile for the isolate.

For cases of cutaneous C. ulcerans infection, exclusion and droplet precautions are not required.

Contacts

Contact Tracing

Only for confirmed* toxigenic C. diphtheria or C. ulcerans.

*Consider providing education for symptom monitoring and offering vaccination to contacts of a suspected case where there is high clinical suspicion of respiratory diphtheria and there is likely to be a delay in receiving results of cultures or toxin testing.

Purpose

To identify and treat unrecognised cases. To treat incubating disease and eliminate carriage. To update vaccinations in the contacts and wider community.

Contact Definition

Individuals who:

• were in contact with the case during their infectious period

AND

• are household or household-like members (including intimate partners)

OR

• were directly exposed to the infectious site without appropriate protection:
  • to the oral secretions of a respiratory case, e.g. intimate kissing/sexual contacts, or via mouth-to-mouth resuscitation
  • had direct contact with the wound without wearing appropriate PPE

OR

• had prolonged significant interaction with the case, i.e. had close contact for 20 hours or more with the case (e.g. in childcare settings) whilst infectious with an uncovered cutaneous or unmasked respiratory case.

Healthcare workers (HCWs) who have used appropriate transmission-based precautions do not need to be considered contacts and can be provided with education and updated vaccination as appropriate. Further risk assessment may be required for HCWs who have undertaken wound care of cutaneous cases, to identify if any potential respiratory exposure has occurred during wound care, e.g. vigorously washing the wound or irrigating the wound under pressure.

Further guidance, refer to Appendix C: Contact risk classification and management.

An Expert Advisory Group meeting may be beneficial in complex situations or those extraneous to these guidelines.

If the initial nasopharyngeal and/or throat swabs of a case with cutaneous diphtheria are positive (indicating nasopharyngeal carriage), then manage contact tracing as per a confirmed respiratory case.

Investigation

Refer to Appendix C: Contact risk classification and management.

All contacts should have their immunisation history checked.

Medium and high-risk contacts as defined in Appendix C (regardless of their vaccination status) should have throat, nasopharyngeal and any wound swabs taken for culture (ideally before the commencement of antibiotics) and be advised regarding surveillance for 5 days from direct exposure for evidence of disease. In some situations where persons or their carer/s are unable to adequately self-monitor, this may require daily clinical examination for symptoms and signs of diphtheria.

If an asymptomatic contact returns a positive nasopharyngeal or throat swab, they should be managed as a case of respiratory diphtheria, including appropriate contact tracing.

Prophylaxis

Once contact is identified as requiring prophylaxis, refer to Appendix D: Antibiotic prophylaxis for contacts and treatment for carriers (asymptomatic cases) of diphtheria for recommended antibiotics and dosages.

Vaccination

Previously vaccinated contacts should receive a booster dose of diphtheria toxoid if more than one year has elapsed since their last dose. Unvaccinated or incompletely vaccinated contacts should complete a primary or catch-up course of diphtheria vaccination. Pregnant contacts should receive ADT immediately and can still have dTPa from 20 weeks gestation. Refer to the current edition of Diphtheria | The Australian Immunisation Handbook for vaccination details.

Restriction and isolation

High-risk contacts of C. diphtheria (Appendix C: Contact risk classification and management) should minimise interaction with people vulnerable to diphtheria until 72 hours of an appropriate course of antibiotics have been completed OR until cultures from the nose, throat and any lesions are proved to be negative for toxigenic diphtheria bacilli, whichever is shorter.

Vulnerable individuals include infants aged 6 months and under, the sick, the elderly and those requiring dependent care, and immunosuppressed individuals. In the household this requires avoidance and in work situations this requires exclusion from the workplace.

Healthcare workers who have cared for a case of respiratory diphtheria without appropriate transmission-based precautions should be excluded from patient care until negative cultures are returned.

Exclusion of asymptomatic contacts of C. ulcerans is generally NOT required.

Counselling

All contacts should be advised of the nature of the infection and its mode of transmission.

Medium and high-risk contacts as defined in Appendix C should be advised to monitor for symptoms of diphtheria for 5 days from contact and seek medical advice promptly should symptoms appear.

C. ulcerans: Due to the zoonotic nature of C. ulcerans infection, it is important to identify any potential animal source. Where the case’s infection has been acquired in Australia and the case has had contact with animals during the incubation period, liaison with animal health authorities is recommended to discuss the practicality of screening companion animals, livestock or other identified animals.

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Preventive measures

The most effective preventive measure is widespread vaccination with diphtheria toxoid. Other preventative measures include:

• maintaining high Australian childhood and adult vaccination coverage rates, including an emphasis on those at high risk, e.g. HCWs and travellers
• supporting vaccination programs among other countries in the Oceania region as required
• encouraging and educating on good skin and hand hygiene
• encouraging people to seek health review of non-healing wounds.

Appendix A: Public health response for toxigenic diphtheria cases in priority communities

It is highly recommended that early consultation and partnership with community leaders and representatives is initiated when managing diphtheria cases and contacts in a First Nations community. If an outbreak control team is convened, consider including appropriate Aboriginal and Torres Strait Islander stakeholders. This member could be the hospital and health service First Nations Executive Director, Aboriginal and Torres Strait Islander community-controlled organisation CEO or council nominee.

In addition to case and contact investigation and management as outlined above, consider the following additional public health actions in a priority community.

Close Contacts (toxigenic cutaneous and respiratory diphtheria)

Contacts in some social settings may require consideration for close contact status, with likelihood of transmission to be considered based on

• location and type of social setting,
• infectiousness, duration, and level of interaction with the case.

Community Contacts (toxigenic cutaneous and respiratory diphtheria)

Public health management for close-knit communities, including remote discrete First Nations communities, may include:

• alert all local health services and community of the risk of severe toxigenic respiratory diphtheria (even if case has cutaneous diphtheria) and the need for primary and booster vaccinations
• ensure referral hospitals have supply of DAT
• opportunistically check vaccination status and offer catch-up and booster doses to whole community
• ensure all children aged < 20 years are up to date with the national immunisation program schedule and active catch up for any who are overdue
• consider an active outreach vaccination campaign in the community, assessing:
  • low vaccination rates and/or booster coverage indicated from existing data
  • new or increasing incidence of toxigenic diphtheria cases
  • one or more respiratory diphtheria cases
  • community concerns and support raised in community consultation
  • adequate local staffing and feasibility

Appendix B: DAT treatment for cases of respiratory diphtheria

Diphtheria antitoxin (DAT) neutralises circulating toxin. DAT is considered the mainstay of treatment for respiratory diphtheria, while antibiotics are required to eradicate the organism, stop further toxin production, and help prevent transmission. Toxin already bound to tissue is unaffected, meaning DAT does not reverse symptoms caused by bound toxin. Rather, it limits disease progression making early administration critical, with the degree of protection being inversely proportional to delay in administration.

DAT is not listed on the Australian Register of Therapeutic Goods and must be accessed using the Special Access Scheme (SAS) of the Therapeutic Goods Act 1998.  Queensland holds a limited supply of DAT and the standard operating procedure which outlines how to obtain DAT is found at: Guidance for Accessing Diphtheria Antitoxin.

Note that approval for the use of DAT is required from the on-call Infectious Diseases Physician servicing the treating HHS. The final decision to administer DAT rests with the treating clinician.

DAT is derived from equine serum. There is the potential risk of a hypersensitivity reaction ranging from acute anaphylaxis to serum sickness. Sensitivity testing should be considered in accordance with the Product Information before giving antitoxin.

Adults and children receive the same dose.  Preferred route is intravenous, particularly in severe cases.  DAT may be given intramuscularly in mild or moderate cases.  Additional doses may be considered based on the person’s symptoms and response at the request of the treating team, noting that repeated DAT doses are not usually associated with additional benefit.

DAT treatment for cases¹⁰

For further detail, refer to CDC: Expanded Access Investigational New Drug (IND) Application Protocol: Use of Diphtheria Antitoxin (DAT) for Possible Diphtheria Cases.

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Appendix C: Contact risk classification and management

Management

High Risk Exposure – 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).

At minimum:

• Provide information and advice to monitor for symptoms for at least 5 days after contact.
• Swab^# nasopharynx and throat, and any skin lesions.
• Provide clearance antibiotics.
• Avoid contact with vulnerable populations (infants aged ≤6 months, sick, elderly, those requiring dependent care, and immunosuppressed individuals) until swabs returned negative result or 72 hours from commencement of appropriate antibiotics, whichever is shorter. In the household this requires avoidance and in work situations this requires exclusion from the workplace.
• Exclusion of asymptomatic contacts of C. ulcerans is generally NOT required.
• Recommend a booster dose of vaccine if more than 12 months since last dose received
• Primary or catch-up course of vaccination if unvaccinated or incomplete.

Medium Risk Exposure – Uncertain exposure requiring further risk assessment.

At a minimum:

• Provide information and advice to monitor for symptoms for at least 5 days after contact.
• Swab^# nasopharynx and throat, and any skin lesions.
• Recommend a booster dose of vaccine if more than 12 months since last dose received.
• Primary or catch-up course of vaccination if unvaccinated or incomplete.

Additional public health measures will depend on consideration of risk factors +/- EAG:

• infectiousness of case during exposure event
  • symptomatic respiratory cases are likely to create higher risk exposures than cutaneous cases
  • PPE use by the case and contact, e.g. mask / coverage of wound
• type and duration of interaction
  • significant interaction, e.g. well known to case / close friend
  • prolonged single interaction rather than multiple short interactions
• vaccination status of contact
• potential co-exposure to upstream cases / multiple case exposures.

# Swabs should ideally be combined nasopharyngeal (NP) 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.

Low risk – 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.

Contact definition and risk category

*Aircraft:
The risk of transmission of C. diphtheriae on an aircraft is low, especially for flights of less than 8 hours duration. Should a case of symptomatic respiratory diphtheria travel on a long-distance flight while infectious, the passengers seated immediately adjacent to them should be considered household-like contacts.

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

• someone subsequently diagnosed with respiratory diphtheria travelled on a long-distance flight during their incubation period.
• someone with cutaneous diphtheria and negative initial nasopharyngeal and throat swabs travelled on a long-distance flight.

Consider contact tracing adjacent seats of a long-distance flight when someone with cutaneous diphtheria travelled with an uncovered infected wound and/or returns positive initial nasopharyngeal and/or throat swabs. In these instances, it is recommended to call an EAG to discuss further.

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Appendix D: Antibiotic prophylaxis for contacts and treatment for carriers (asymptomatic cases) of diphtheria

Please note that varying degrees of penicillin resistance are increasingly being documented in Queensland.  Choice of antibiotics and dosing regimen should take into account antibiotic sensitivities, clinical tolerance and nature of contact with the case. Check sensitivities of isolate before recommending antibiotic prophylaxis and seek the advice of an infectious diseases physician if sensitivities are pending or conflict with recommended antibiotics. Alternative antibiotics may be recommended.

First line antibiotics for use in contacts and asymptomatic carriers

¹ Amoxicillin may be an appropriate option for isolates reported as having “intermediate” susceptibility to penicillin (equates to susceptible increased exposure); discuss with Infectious Diseases Physician and/or Clinical Microbiologist. Isolates reported as resistant to penicillin are considered resistant to amoxicillin unless testing indicates otherwise.
² Where a macrolide antibiotic is recommended, discuss with Clinical Microbiologist to ensure sensitivity testing is undertaken.

Alternative antibiotics for use in adults ≥12 years based on available sensitivities

¹ Use in adult contacts ≥50 kg in weight. Doxycycline is contraindicated in pregnancy and breast feeding.
² Where penicillin and macrolide antibiotics are contraindicated, not tolerated or impractical, doxycycline may be considered for children aged 8-11 years who weigh ≥50 kg.

Note: Diphtheria antitoxin has no proven role in the prophylaxis of contacts or the treatment of carriers.

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References

1. Acosta A TT. Diphtheria. In: Ryan E HD, Solomon T, Aronson N, Endy T, editor. Hunter's Tropical Medicine and Emerging Infectious Diseases: Elsevier; 2020. p. 439-45.
2. Breakwell L SR. Diphtheria and Other Corynebacterium Infections. In: Goldman L SA, editor. Goldman-Cecil Medicine. 26 ed: Elsevier; 2020. p. 1881-4.
3. Horn K J-VA, Arenas V, Andani S, Janoff E, Clark S. Corynebacterium Species Inhibit Streptococcus pneumoniae Colonization and Infection of the Mouse Airway. Front Microbiology. 2022;12.
4. Hempenstall A SJ, Marquardt T, Fisher V, Johnson J. Clinician alert: toxigenic diphtheria cases across North Queensland are on the rise. Medical Journal of Australia. 2023;218(5):238-.
5. Saleeb P. Corynebacterium diphtheriae (diphtheria). In: Bennett J. E.; Dolin RB, M. J., editor. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. Philadelphia, PA: Elsevier; 2020.
6. Truelove S KL, Moss W, Chaisson L, Macher E, Azman A, Lessler J. Clinical and Epidemiological Aspects of Diphtheria: A Systematic Review and Pooled Analysis. Clinical Infectious Diseases. 2020;71:89-97.
7. Wagner K WJ, Crowcroft N, 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.
8. Communicable Diseases Network Australia. Diphtheria: Australian national notifiable diseases case definition. In: Australian Government Department of Health and Aged Care, editor. Canberra: Commonwealth of Australia; 2004.
9. National Health Medical Research Council. Australian Guidelines for the Prevention and Control of Infection in Healthcare (2019). In: NHMRC, editor. Canberra: Commonwealth of Australia; 2019.
10. United States Centre for Disease and Prevention Control. Expanded Access Investigational New Drug (IND) Application Protocol: Use of Diphtheria Antitoxin (DAT) for Possible Diphtheria Cases. In: United States Centre for Disease and Prevention Control, editor. 2022.

Revision History