Guidance

Public health management of toxigenic C. ulcerans in companion animals

Published 21 March 2023

Applies to England

Executive summary

These guidelines present the rationale and recommendations for the control of toxigenic Corynebacterium ulcerans (C. ulcerans) in companion animals in England. They cover the investigations necessary to confirm the presence of toxigenic C. ulcerans in animals, how these animals should be managed, and the management of close human and animal contacts of a confirmed animal case. Separate guidance for the public health control and management of diphtheria in humans in England is available, which covers the management of humans with diphtheria and their close contacts.

This information has been developed in response to changes in local epidemiology, including an increasing number of toxigenic C. ulcerans cases in companion animals reported and managed in the United Kingdom and overseas. Furthermore, these guidelines highlight and emphasise the importance of multiagency working between human and animal health organisations.

The guidelines are intended for those involved in the public health control of toxigenic C. ulcerans associated with companion animals in England:

• health protection teams in the UK Health Security Agency (UKHSA)
• NHS staff at local and national levels in England
• Animal and Plant Health Agency (APHA) staff

Background and rationale

Background

Respiratory or cutaneous diphtheria is caused by toxigenic strains (those expressing diphtheria toxin) of the bacteria Corynebacterium diphtheriae (C. diphtheriae), C. ulcerans, and, very rarely, Corynebacterium pseudotuberculosis (C. pseudotuberculosis). C. ulcerans and C. pseudotuberculosis are zoonotic pathogens, and detection of either in an animal may require public health consideration, as toxigenic infections in animals may go on to cause diphtheria in humans.

In contrast to C. ulcerans and C. pseudotuberculosis, reports of isolation of both toxigenic and non-toxigenic C. diphtheriae from animals are rare. Although C. diphtheriae is not considered zoonotic, toxigenic strains have been isolated from equine and canine wounds. Non-toxigenic C. diphtheriae has also been isolated from companion, farm and wild animals, including non-toxigenic toxin gene-bearing (NTTB) strains (1). In recent years, the only diphtheria toxin-expressing isolates from animals have been C. ulcerans.

At the time of publication of this guidance, it has been many years since the last reported toxigenic C. diphtheriae isolates were identified in animals in England. However, toxigenic C. diphtheriae was isolated from equine wounds in Ireland in 2006 (2) and in Belgium in 2018 (3).

If toxigenic C. diphtheriae or C. pseudotuberculosis is identified in a companion animal, a similar approach to public health management and control for toxigenic C. ulcerans should be taken, in discussion with the incident management team (IMT).

For information on how to manage a toxigenic C. ulcerans case in a human and more detailed information on the background, clinical features and microbiology of diphtheria, see the guidance on the public health control and management of diphtheria in England.

C. ulcerans in humans

The first report of C. ulcerans infection was in 1920 when the organism was isolated from human pharyngeal lesions and diphtheria toxin expression by this species was demonstrated (4). C. ulcerans has been associated with classical diphtheria with pseudomembrane (4 to 8) as well as with milder respiratory and/or cutaneous symptoms (9 to 13). From 1994 to 2021 there were 8 deaths attributed to diphtheria in England and Wales. Isolates were received from 7 cases; 6 were toxigenic C. ulcerans and one was toxigenic C. diphtheriae (14).

To date, person-to-person spread of C. ulcerans has not been definitively documented, and the majority of swabs taken from close human contacts of cases of C. ulcerans have been culture-negative (7, 9, 12, 15). However, in 3 incidents, reported in 1996, 1998 and 2014, toxigenic C. ulcerans was isolated from asymptomatic contacts of cases, raising the possibility of person-to-person transmission (16, 17).

In 1996, the asymptomatic sibling of a confirmed case of toxigenic C. ulcerans case also tested positive for toxigenic C. ulcerans, but no data regarding domestic pet contact was recorded. In 1998, toxigenic C. ulcerans was isolated from the son of a confirmed case of toxigenic C. ulcerans case. Swabs from domestic pets were obtained but C. ulcerans was not isolated. In 2014, the asymptomatic grandmother of a confirmed toxigenic C. ulcerans case was also found to be toxigenic C. ulcerans positive. The grandmother had no close contact with the animals on the farm they both lived on. However, testing of the animals was not possible.

Clinical diphtheria in humans is a notifiable disease regardless of the species.

C. ulcerans in animals

C. ulcerans is usually a commensal on the mucous membranes of most animals, although animals infected with C. ulcerans can develop nasal congestion, streaming eyes and sneezing. C. ulcerans bacteria can also cause skin lesions, ulcers, or abscesses in animals (18). The organism has a wide host range and has been isolated from domestic, wild, captive, and research animals including goats, pigs, dogs, cats, roe deer, ground squirrels, otters, camels, monkeys, whales, wild boars, ferrets, water rats, owls, shrew-moles, hedgehogs, foxes, horses, rhinoceroses, birds and others (15, 19 to 35).

However, the natural history of C. ulcerans in animals is not well understood. A prospective study of nasal samples from healthy cats and dogs in the UK found carriage of C. ulcerans in 0.42% (2 out of 479) of dogs and 0 out of 72 cats, whereas in a retrospective study in animals with signs of upper respiratory tract infection observed rates were 0.53% (1 out of 189) in dogs and 6.3% (4 out of 64) in cats (18).

Two studies investigating the prevalence of C. ulcerans in companion animals in Japan showed that 5.4% (2 out of 37) of cats with a primary complaint of rhinitis had toxigenic C. ulcerans detected (28) and 7.2% (42 out of 583) of asymptomatic (36) dogs throat swabs were positive for toxigenic C. ulcerans.

There is no statutory requirement for veterinary laboratories to report C. ulcerans (toxigenic or non-toxigenic) in animals to the Animal and Plant Health Agency (APHA).

Zoonotic transmission of C. ulcerans

C. ulcerans infection in humans is rare: a review in 2016 found that only 19 cases were reported in the international literature between 2011 and 2016 (37). This is likely an underestimate as many case reports have been written in local languages and no cases from Africa, India or China were identified. C. ulcerans infection in humans has been associated with prolonged close contact with animals (for example, pets in the home, through working on a farm or as a veterinarian) or consumption of unpasteurised milk and dairy products.

In animals, C. ulcerans may infect the bovine udder and, in the past, an association between human C. ulcerans infection and drinking raw milk and unpasteurised milk products has been observed (9, 10). In more recent years, human toxigenic C. ulcerans infections have been associated with close contact with domestic and companion animals, such as cats and dogs (16, 20, 25, 36, 38 to 48).

Between 2005 and 2021, 10 cases of confirmed zoonotic transmission from companion animals to humans were reported in the scientific literature:

• 2 cases from Germany (39, 42)
• 2 cases from France (43, 45)
• 1 case from Switzerland (20)
• 5 cases from Japan (44, 46 to 48)

Clinical presentation of the human cases included skin conditions such as:

• cutaneous ulcers (20)
• cellulitis (43)
• severe necrotizing fasciitis (39)

Respiratory presentations ranged from sore throat, fever, and fibrinous rhinitis (42) to refractory pharyngitis (44, 45), severe pneumonia (47), cyanosis (48), and respiratory arrest (46, 48). Two human deaths were reported (43, 46).

In 3 of the 10 human cases, clinical signs in companion animals (cats in 2 cases, dog in one case) were reported. These animals presented with:

• lesions (cat (20, 43))
• mouth ulcers (dog (20, 43))
• discharging eyes (cat (44, 45)).

Two animals did not show clinical signs:

• 1 dog (39)
• 1 cat (42)

Information on clinical signs in animals in the remaining 5 case reports was not available. These findings suggest that transmission from an asymptomatic animal to a human may be possible.

Recent experience in England

Between 2009 and 2021, there were 34 toxigenic C. ulcerans human cases reported in England. Of the 30 cases where hospitalisation information was available, 12 cases were hospitalised, of which 4 cases died. These 4 cases were all over the age of 55 years and vaccination status was either unknown or none was recorded on their GP records.

All 34 cases reported contact with domestic animals. Contact with non-domesticated animals was also noted for 7 cases, and 3 cases reported a history of consuming unpasteurised dairy products. The evidence on companion animal transmission to humans is limited because of the relatively small number of animal cases, high exposure prevalence to companion animals in the general population, and lack of (or timing of) swabbing of animal contacts.

However, evidence is slowly accumulating. In England, since 2009, swabs have been taken from 45 companion animals associated with 24 human cases, all from dogs and cats. For 7 of these human cases, at least one companion animal screened positive for toxigenic C. ulcerans (4 dogs and one cat; 3 human cases had contact with the same positive dog). C. ulcerans was not detected in any of the other companion animals that underwent swabbing, although a zoonotic source of infection was considered most likely in these incidents. Swabs were also taken from 16 kid goats associated with one of the human cases; C. ulcerans was not detected in any of these samples.

In 2017, in addition to testing human and animal isolates associated with human cases, the National Reference Laboratory began testing animal isolates not associated with human cases to inform public health action. Between 2017 and 2021, there have been 14 animal index cases of toxigenic C. ulcerans in England, with the number of cases per year varying from one to 7.

Animal index cases have been reported in 7 dogs, 6 cats and one horse, presenting with a range of respiratory and wound infections.

Of the 7 dogs, 3 were initially swabbed at their veterinary surgery because of respiratory symptoms, while the other 4 dogs were initially swabbed due to a skin lesion or abscess. No human or animal contacts swabbed as a result of public health follow-up were positive for toxigenic C. ulcerans, although one human household contact was positive for C. pseudodiphthericum. Five human household contacts experienced symptoms including a sore throat, fever and a cough, however, the causes of these symptoms were not determined.

Of the 6 cats, 2 were initially swabbed due to respiratory symptoms, while the other 4 were swabbed as a result of wounds or skin lesions (in one case an infected dew claw). No human or animal contacts swabbed as a result of public health follow-up were positive for toxigenic C. ulcerans. Two human veterinary contacts experienced symptoms including a sore throat and a cough, however, the causes of these symptoms were unable to be determined.

The horse presented with persistent unilateral nasal discharge and expelled a membrane from its nose. A nasal swab demonstrated growth of C. ulcerans and Streptococcus zooepidemicus. Three owner contacts and over 40 veterinary contacts were followed-up. One human veterinary contact reported a sore throat and a positive swab for C. diphtheriae, but this was found to be non-toxigenic. Approximately 20 horses in the same livery yard were followed-up as animal contacts; all remained clinically well (49).

To date, none of the over 130 human contacts followed-up as being associated with animal index cases in England have been found to be positive for toxigenic C. ulcerans on swabbing. There is a likelihood of underreporting of human contacts associated with animal index cases as C. ulcerans is not notifiable in animals.

The epidemiology of toxigenic C. ulcerans cases in England between 2009 and 2021 is summarised in Appendix 4.

Rationale for the guidelines

As described above, reported incidents of confirmed toxigenic C. ulcerans are rare in animals. Although C. ulcerans infection is not notifiable in animals, there may be potential risks to public health from this infection in animals that may require public health involvement to manage this risk.

These guidelines, therefore, aim to:

• raise awareness among clinicians and prompt consideration of diphtheria as part of the differential diagnoses if contact with companion animals is reported
• assist health protection staff in undertaking risk assessments
• provide clarity on clinical and public health actions that should be taken based on the risk assessment for the different potentially toxigenic corynebacterial

Investigation of animal index cases

Criteria for animal isolates to be submitted for toxin testing

Primary animal samples may be tested for a variety of reasons at private veterinary laboratories, and C. ulcerans may be detected in animals with wound or respiratory infections.

The UKHSA Respiratory and Vaccine Preventable Bacteria Reference Unit (RVPBRU) at Colindale is the only laboratory in the UK that provides confirmation of the toxigenicity status of C. diphtheriae, C. ulcerans and C. pseudotuberculosis. The laboratory is principally for the testing of human isolates. However, in certain circumstances and following agreement from the laboratory, animal isolates may be tested where there is a potential risk to public health.

For an animal isolate to be considered for submission to UKHSA RVPBRU, it must fulfil all of the following criteria:

• potential risk to public health from the transmission of the infection in an animal
• putative identification of C. ulcerans to species level, preferably with Matrix Assisted Laser Desorption/Ionization – Time of Flight Mass Spectrometry (MALDI-TOF MS)

If a veterinary lab does not have access to MALDI-TOF, then alternative options for identification include Hoyle’s and Tinsdale agar. Commercial phenotypic identification systems such as API Coryne (bioMérieux), and Vitek (bioMérieux) identify isolates which do not belong to one of the 3 potentially toxigenic species.

Testing of animal isolates at RVPBRU will generally only be carried out during regular working hours and there may be a charge associated with the testing of animal isolates.

Sending an isolate for toxigenicity testing

Veterinarians or veterinary laboratories who are submitting an isolate for C. ulcerans toxigenicity testing should notify the UKHSA RVPBRU laboratory by telephone before sending potentially toxigenic animal isolates for toxigenicity testing:

• Bacteriology triage telephone: 0208 327 7887
• Vaccine Preventable Bacteria Section telephone: 0208 327 7331

An isolate should only be sent to Colindale once the RVPBRU have agreed to accept an isolate for toxigenicity testing.

Always use the RVPBRU Request Form (R3) and ensure full contact telephone numbers are provided on the form, to allow timely reporting of results. Please ensure the isolate and not the sample itself is sent for toxigenicity testing, as this would cause substantial delays.

Isolates may be sent on agar slopes (blood, chocolate or Loeffler) or transport swabs (for example, Amies).

Send isolates to:

UK Health Security Agency Colindale
Vaccine Preventable Bacteria Section
Bacteriology Reference Department
61 Colindale Avenue
London
NW9 5HT

To ensure timely processing, isolates should be sent via courier.

Service

Testing of potentially toxigenic animal isolates at RVPBRU which are not associated with a human case will generally only be carried out during routine working hours. Those known to be linked with human cases will be prioritised accordingly in discussion with the health protection team (HPT) and the RVPBRU.

Laboratory safety

Although rare, laboratory-acquired diphtheria infections have been reported. In the UK toxigenic C. ulcerans is classified by the UK Advisory Committee on Dangerous Pathogens (ACDP) as Hazard Group 2. See the guidance on public health control and management of diphtheria in England for further information on laboratory safety.

All staff that routinely handle cultures of potentially toxigenic Corynebacteria should be fully vaccinated (including booster vaccinations) as recommended by the Green Book.

Animal case definitions

Animal cases should be classified according to the following laboratory criteria:

• confirmed case of toxigenic C. ulcerans: laboratory confirmation of a toxigenic strain^{[footnote 1]}
• probable case of toxigenic C. ulcerans: isolation of C. ulcerans at a local laboratory but toxigenicity status has not yet been confirmed

Laboratory confirmation and timing of public health actions

Recent experience in England has shown that C. ulcerans isolates are much more likely to turn out to be Elek positive, that is, they are expressing the toxin gene, in comparison to C. diphtheriae. Since August 2017 and up to the end of 2021, all 14 toxin positive animal isolates confirmed by polymerase chain reaction (PCR) at the RVPBRU also turned out to be Elek positive. Therefore public health action should be initiated on PCR confirmation from RVPBRU, rather than awaiting the Elek result.

Once an animal isolate has been confirmed^{[footnote 1]} as toxigenic C. ulcerans (laboratory identification and confirmation of diphtheria: isolation of diphtheria toxin-producing corynebacteria (indicated by PCR detection of toxin gene and confirmed by Elek test) from a clinical specimen by a reference laboratory), RVPBRU will inform the referring veterinary laboratory of the result.

RVPBRU will also inform the UKHSA Emerging Infections and Zoonoses (EIZ) team of the result, who will also ensure the relevant HPT and APHA are informed.

Human public health actions following toxigenicity results:

• for an animal case confirmed as a toxigenic strain, public health management of the case and contacts (human and animal) should be coordinated jointly by public and animal health colleagues
• for an animal case with NTTB corynebacteria (PCR diphtheria toxin gene positive, Elek negative), public health actions can be stopped if they have been initiated; for more information on NTTB, see the guidance on the public health control and management of diphtheria in England
• for an animal case which is discarded due to negative results, (that is, it is not a toxigenic strain), public health actions can be stopped if they have been initiated. Discontinue investigation and management of contacts; further management of the animal case will be through veterinary services

For more information on toxigenicity testing of human samples, see the guidance on the public health control and management of diphtheria in England.

Management and investigation of animal cases and their human and animal close contacts

See the algorithm for the management of toxigenic C. ulcerans in companion animals.

Incident management team (IMT) membership

If necessary, an IMT should be considered by the local HPT. If a notification is received by the HPT over a weekend, initial information gathering and public health actions should be commenced but it is usually not necessary to call an IMT out of hours unless there are significant public health concerns.

Membership of the IMT will vary depending on local circumstances, but will typically include:

• consultant in consultant in health protection or communicable disease control
• local NHS consultant microbiologist
• representative from UKHSA RVPBRU and EIZ
• representative from the APHA
• UKHSA communications team

See Appendix 1 for a draft IMT agenda.

Classification and management of close human contacts

Potential routes of transmission from animal to human include direct contact with cutaneous diphtheria lesions or infected secretions of an infected animal. Contact with articles soiled with the discharge of infected secretions or lesions from animals may also play a role in transmission. The potential risk of transmission is likely to be related to the closeness, nature and duration of contact.

The maximum incubation period for diphtheria is 10 days. However, there may be a longer duration of carriage in asymptomatic human carriers but there is little evidence. Duration of carriage in animals is not well understood, therefore extrapolating from the understanding in humans, close contacts should be identified from 10 days before onset of diphtheria clinical signs in an animal.

Definition of close human contacts

Close human contacts are defined as follows:

• members of the household – this includes owners and/or members of the household in which a companion animal lives
• those who regularly handle and touch the animal, for example, dog walker, dog sitter, extended household members who may have had close contact with the animal before the diagnosis of toxigenic C. ulcerans
• those who are involved in the animal’s care and not wearing appropriate personal protective equipment (PPE) – this might occur while, for example, feeding the animal, handling the animal’s bedding, providing wound care
• veterinary staff not wearing appropriate PPE – for wound care or any aerosol, respiratory secretion generating procedure, appropriate PPE would include a fluid-repellent surgical face mask, disposable gloves and, ideally, an apron

Visitors to a household or other setting who have had no or brief contact with the animal, or an individual in a veterinary setting wearing appropriate PPE are not considered to be close contacts.

Higher risk exposures include direct exposure to animal fluid or tissue with a potentially high bacterial load (for example discharging wound or pharyngeal membrane) with no PPE. The IMT should consider if it is appropriate to offer chemoprophylaxis to human contacts who have had higher risk exposures. High-risk exposures that occurred more than 10 days ago should be discussed by the IMT.

Management of close human contacts

This will be led by the local HPT. The process involves:

1. Assessing the degree of contact with animal

Determine if the human exposure fulfils the criteria for close contact. If yes, consider whether this could have been a high-risk exposure (see section on Antibiotic treatment).

2. Informing human contacts and advising them to self-monitor

Health protection staff should provide the case and contacts with a fact sheet on diphtheria (see Appendix 2), check the health status of close contacts, explain the symptoms to be aware of (fever, sore throat, swollen neck glands, development of a membrane, skin lesions), and advise them to seek urgent medical attention if they become unwell. Close contacts should be advised to self-monitor for 10 days after the date of their last exposure to the animal. For those unable to self-monitor, the health protection staff should advise their carer or otherwise designated individual.

Contacts of an infected animal should be advised to wash their hands after handling the animal or animal environment, particularly after treating wounds, cleaning discharge from the nose, eyes and so on. The owner should also be encouraged to avoid close contact with the infected animal and prevent the animal from licking other animals or humans until treatment has finished and negative clearance swabs have been achieved.

3. Exclusion from work or school

Exclusion of close contacts from work is generally not advised unless they work in high-risk occupations such as healthcare workers, those who work with unimmunised people or those involved in milk production. This list is not exhaustive and there may be other instances where exclusion would be appropriate. Usually, individuals in occupations listed above should stay off work until they receive negative swab results, though individual circumstances can be considered.

4. Swabbing

All close human contacts should be offered a swab (nasopharyngeal and throat swabs and any new skin lesions if present) via their GP and samples sent for bacterial culture to a local or regional public health laboratory (this will differ depending on regional arrangements). Health protection staff should inform the case’s GP of the situation. Request forms must be labelled for Corynebacterium ulcerans (or C. ulcerans) screening to ensure the laboratory uses the appropriate selective media for culture or that corynebacterial grown on non-selective media are followed up as appropriate. These samples should be sent, with warning, to the local laboratory or regional public health laboratory (isolates would be forwarded to Colindale by the local laboratory for toxigenicity testing only if a culture is positive for C. ulcerans).

If a human contact’s swab is positive for toxigenic C. ulcerans, they should be managed as a confirmed case of diphtheria (as per the guidance on the public health control and management of diphtheria in England). Public health action should also be initiated if a human contact is C. ulcerans culture positive but results from toxigenicity testing are awaited.

5. Chemoprophylaxis

Antibiotic chemoprophylaxis is not required for most human contacts of animals with toxigenic C. ulcerans. However, if the exposure to the animal is assessed as being particularly high risk (for example, direct contact with secretions from a wound, handling of a diphtheritic membrane) or if there are concerns about clinical vulnerability of a contact, this should be discussed with the individual’s GP.

Decisions on recommendations for chemoprophylaxis should be made by the local HPT using locally agreed chemoprophylaxis pathways.

For detailed information on chemoprophylaxis please see the guidance on the public health control and management of diphtheria in England.

6. Immunisation

The vaccination status of close human contacts should be assessed.

Close contacts of a confirmed animal diphtheria case who are appropriately immunised for age should be immunised with a diphtheria-toxoid-containing vaccine, unless a diphtheria-toxoid-containing vaccine has been given within the previous 12 months. For those who are not appropriately immunised, a diphtheria-containing dose should be given immediately, and the schedule completed according to the guidelines available on vaccination of individuals with uncertain or incomplete immunisation status.

Infections may still occur in fully vaccinated individuals as the diphtheria toxoid vaccine prevents the symptoms of infection, but does not prevent acquisition of carriage.

Management of laboratory contacts

Individuals who may have been exposed to C. ulcerans in a laboratory (without appropriate PPE) should be followed up as close human contacts as above. If needed, they should be offered a booster of diphtheria-containing vaccine. If required, the RVPBRU laboratory at Colindale offers a test to determine the levels of diphtheria toxin-neutralising antibodies in the serum. These can be submitted using the R3 form: vaccine preventable bacteria section request form via the GP or local laboratory route. There is a charge associated with this service.

Management of index animal

Animal health issues fall under the remit of APHA and are not the responsibility of the HPT. However, awareness of the management of animal cases and contacts is important as it may impact on public health. The likely animal actions APHA will advise are therefore included here for broader context and understanding to assist in collaborative management of the public health situation.

Antibiotic treatment

All animal specimens should be collected before antibiotic treatment is started, if possible. If antibiotics have already been started then samples should still be taken.

APHA will advise on appropriate antibiotic treatment of animals. Antimicrobial susceptibility results will guide appropriate antibiotic choices. Where daily administration of tablets is not possible, a long-acting antibiotic injection may be advised. To confirm clearance of toxigenic C. ulcerans, repeat swabs should generally be taken 5 to 7 days following completion of the antibiotic course. If the animal remains positive for C. ulcerans on repeat swabs, APHA will advise on further management. Where there is more than one companion animal present in a defined setting but only one tests positive for toxigenic C. ulcerans, APHA may recommend treatment of all animals due to the risk of transmission of infection between animals in the household through close contact or sharing of food or water bowls.

Isolation

APHA will advise on the management of animals. However, to minimise the public health risks from potential onward transmission of infection from infected animals, there should be consideration to minimise the contact between the index animal, and other animals or people outside the household; APHA will provide advice on the length of isolation required. If possible, contact between the index animal and members of the household should be limited for at least 48 hours after beginning antibiotic treatment.

Environmental contamination or fomites

There is little evidence of transmission of C. ulcerans through the environment or fomites and it can be assumed to be very rare. APHA may be able to provide advice in specific circumstances. However, once household pets have completed their course of antibiotics, bedding, bowls and toys should be thoroughly washed. It is recommended that they are hot washed, that is, with water over 60°C. If it is not possible to wash bedding, the owners should consider replacing it if possible.

Close animal contacts

Definition of close animal contact

The IMT should explore if any other animals are considered to be close contacts of the index animal and should refer to APHA for further risk assessment. Animals would only be considered close contacts if they have had intimate or regular close contact with the index animal. For example, dogs who briefly interact while out on a walk would not be considered close contacts.

Examples of animals that would be considered close contacts include animals that:

• live in the same household as the index animal (for example, other companion animals)
• regularly attend the same setting as the index animal (for example, they share a dog sitter or attend the same pet daycare centre)
• may have had close contact with an undressed wound, or been exposed to respiratory droplets from the index animal
• share food or water bowls with the index animal
• share bedding or toys with the index animal
• engage in mutual grooming with the index animal

Management of close animal contacts

Sample collection and testing

APHA responsible for animal health management and will advise on the collection and analysis of animal samples and the management of animals. If the animal with toxigenic C. ulcerans infection has been in close contact with other animals, the health status of these animals should be assessed, and swabs should be taken if possible. If these animals are also positive for toxigenic C. ulcerans, the animal should also be treated as a confirmed animal case (see section on Classification and management of close human contacts).

Sample collection usually involves taking throat swabs from the close animal contacts. Any skin lesions present should also be swabbed. Charcoal swabs should be used for bacterial culture. The swabbing is carried out through the animal’s private veterinary surgeon (PVS), but swabs are then sent to the APHA Regional Laboratory in Starcross, Devon where cultures to identify the presence of C. ulcerans are undertaken. If C. ulcerans is isolated the positive isolates would then be notified to UKHSA RVPBRU and once permission granted, sent for toxigenicity testing.

The natural history of C. ulcerans in animals is not fully understood and animals may pass on the infection to humans without exhibiting signs of illness themselves. As it can be difficult to obtain good quality swabs from some animals and they may no longer be carrying the infection when swabbed, it may not always be possible to confirm the presence of toxigenic C. ulcerans infection in an animal that appears to be the likely source of a human infection.

Cost of animal investigations

While APHA will cover the costs of culturing the swabs taken from animals, there are other costs associated with investigation of animals with possible toxigenic C. ulcerans. These costs will usually need to be covered by the owner.

C. ulcerans is not a notifiable disease in animals and investigation (including swabbing) and treatment are unlikely to be covered by pet insurance policies if the animal is otherwise healthy. Therefore, before testing animal contacts, it is important to discuss who will cover the costs of swabbing by the PVS and the implications of a positive test with the owner. This may include:

• the cost of any private veterinary consultations
• the cost and potential outcome of antibiotic treatment, including possible side effects
• clearance swabs
• potential for further treatment

It is appropriate for veterinary staff from APHA to discuss veterinary issues with the owners or PVS. It is not possible to give an accurate estimate for these costs, as they will vary depending on the size and number of animals involved, the number of appointments needed, the type and amount of antibiotic required, and the PVS involved. The owner is encouraged to request an estimate for these actions and interventions. The IMT should discuss alternative funding options if the owner is unable to cover the costs.

Antibiotic treatment

APHA lead on the management of animals in these cases in collaboration with the PVS. Where there is more than one animal present in a household or other defined setting but only one tests positive for toxigenic C. ulcerans, APHA may recommend treatment of all animals due to the risk of transmission of infection through close contact, shared food or water bowls and so on. Ideally the timing of this antibiotic treatment should be coordinated so that all animals are treated at the same time, to reduce the risk of reinfection within the household.

Contact animals should also ideally have clearance swabs following completion of antibiotics and this should be coordinated with clearance swabs for the index animal. However, this may need to be discussed with the owner by APHA and the PVS, as they would likely incur the cost of any clearance swabs required.

Non-toxigenic C. ulcerans

Non-toxigenic strains of C. ulcerans have been reported in companion animals. There is no public health follow-up required for non-toxigenic C. ulcerans in animals. For more information on non-toxigenic C. ulcerans see the guidance on the public health control and management of diphtheria in England.

Communications

Information should be disseminated promptly and appropriately to human contacts to aid understanding, increase the likelihood that advised behaviours are adhered to, minimise anxiety, and control rumours (a fact sheet can be found in Appendix 2).

It is unlikely that a toxigenic C. ulcerans case in an animal will draw attention from the press, but guidance on what to include in a reactive press statement can be found in the guidance on the public health control and management of diphtheria in England.

HPTs may want to consider liaison with regional communication leads to prepare reactive lines and/or proactively promote public messaging, depending on the scale of the incident.

The EIZ team is running an enhanced surveillance scheme for the investigation into the epidemiology and risk factors for Corynebacterium ulcerans infection linked to companion animals. This will be in the form of a telephone interview with a member of the household and will be conducted by the EIZ team. An appropriate time for conducting the interview will be discussed with the HPT but the household should be informed that a member of the EIZ team will be getting in contact at an appropriate time to gather more information.

References

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2. Gilbert R and others. ‘Corynebacterium ulcerans, a pathogenic microorganism’. Journal of Laboratory and Clinical Medicine 1926: volume 12, pages 756 to 761

3. Fakes R and others. ‘Toxic reaction to Corynebacterium ulcerans’ The Lancet 1970: volume 295, issue 7,641, page 298

4. Sing A and others. ‘Classical diphtheria caused by Corynebacterium ulcerans in Germany: amino acid sequence differences between diphtheria toxins from Corynebacterium diphtheriae and C. ulcerans’ Clinical Infectious Diseases 2005: volume 40, issue 2, pages 325 to 326

5. Meers P. ‘A case of classical diphtheria, and other infections due to Corynebacterium ulcerans‘ Journal of Infection 1979: volume 1, issue 2, pages 139 to 142

6. Gubler J and others. ‘Classical pseudomembranous diphtheria caused by Corynebacterium ulcerans’ Schweizerische Medizinische Wochenschrift 1990: volume 120, issue 48, pages 1,812 to 1,816

7. Hart R. ‘Corynebacterium ulcerans in humans and cattle in North Devon’ Epidemiology and Infection 1984: volume 92, issue 2, pages 161 to 164

8. Bostock A and others. ‘Corynebacterium ulcerans infection associated with untreated milk’ Journal of Infection 1984: volume 9, issue 3, pages 286 to 288

9. Mattos-Guaraldi A and others. ‘First detection of Corynebacterium ulcerans producing a diphtheria-like toxin in a case of human with pulmonary infection in the Rio de Janeiro metropolitan area, Brazil’ Memorias do Instituto Oswaldo Cruz 2008: volume 103, pages 396 to 400

10. Pers C. ‘Infection due to Corynebacterium ulcerans producing diphtheria toxin: a case report from Denmark’ Acta Pathologica Microbiologica Scandinavica Series B: Microbiology 1987: volume 95, issue 16, pages 361 to 362

11. Kisely S and others. ‘Corynebacterium ulcerans: a potential cause of diphtheria’ Communicable Disease Report. CDR Review 1994: volume 4, issue 5, pages R63 to R64

12. UKHSA. ‘Diphtheria: notifications, deaths and laboratory isolates data’ 2022

13. Olson M and others. ‘Gangrenous dermatitis caused by Corynebacterium ulcerans in Richardson ground squirrels’. Journal of the American Veterinary Medical Association 1988: volume 193, issue 3, pages 367 to 368

14. Wagner K and others. ‘Diphtheria in the UK 1986 to 2008: the increasing role of Corynebacterium ulcerans’ Epidemiology and Infection 2010: volume 138, issue 11, pages 1,519 to 1,530

15. Konrad R and others. ‘Possible human-to-human transmission of toxigenic Corynebacterium ulcerans’ Clinical Microbiology and Infection 2015: volume 21, issue 8, pages 768 to 771

16. Abbott Y and others. ‘Toxigenic Corynebacterium ulcerans associated with upper respiratory infections in cats and dogs’ Journal of Small Animal Practice 2020: volume 61, issue 9, pages 554 to 560

17. Contzen M and others. ‘Corynebacterium ulcerans from diseased wild boars’ Zoonoses and Public Health 2011: volume 58, issue 7, pages 479 to 488

18. Corti M and others. ‘Rare human skin infection with Corynebacterium ulcerans: transmission by a domestic cat’ Infection 2012: volume 40, issue 5, pages 575 to 578

19. Eisenberg T and others. ‘Nontoxigenic tox-bearing Corynebacterium ulcerans infection among game animals, Germany’ Emerging infectious diseases 2014: volume 20, issue 3, page 448

20. Foster G and others. ‘Corynebacterium ulcerans in free-ranging otters’ The Veterinary Record 2002: volume 150, issue 16, page 524

21. Fuursted K and others. ‘Non-toxigenic tox gene-bearing Corynebacterium ulcerans in a traumatic ulcer from a human case and his asymptomatic dog’ Microbes and Infection 2015: volume 17, issue 10, pages 717 to 719

22. Hirai-Yuki A and others. ‘Isolation and characterization of toxigenic Corynebacterium ulcerans from 2 closed colonies of cynomolgus macaques (Macaca fascicularis) in Japan’ Comparative Medicine 2013: volume 63, issue 3, pages 272 to 278

23. Katsukawa C and others. ‘Toxigenic Corynebacterium ulcerans isolated from a hunting dog and its diphtheria toxin antibody titer’ Microbiology and immunology 2016: volume 60, issue 3, pages 177 to 186

24. Marini RP and others. ‘Corynebacterium ulcerans in ferrets’ Emerging Infectious Diseases 2014: volume 20, issue 1, page 159

25. Rau J and others. ‘Corynebacterium ulcerans infection in roe deer (Capreolus capreolus)’ Berliner und Munchener Tierarztliche Wochenschrift 2012: volume 125, issues 3 and 4, pages 159 to 162

26. Saeki J and others. ‘The detection of toxigenic Corynebacterium ulcerans from cats with nasal inflammation in Japan’ Epidemiology and Infection 2015: volume 143, issue 12, pages 2,660 to 2,665

27. Schuhegger R and others. ‘Detection of toxigenic Corynebacterium diphtheriae and Corynebacterium ulcerans strains by a novel real-time PCR’ Journal of Clinical Microbiology 2008: volume 46, issue 8, pages 2,822 to 2,823

28. Simpson-Louredo L and others. ‘Corynebacterium ulcerans isolates from humans and dogs: fibrinogen, fibronectin and collagen-binding, antimicrobial and PFGE profiles’ Antonie Van Leeuwenhoek 2014: volume 105, issue 2, pages 343 to 352

29. Tejedor MT and others. ‘Caseous lymphadenitis caused by Corynebacterium ulcerans in the dromedary camel’ The Canadian Veterinary Journal 2000: volume 41, issue 2, page 126

30. Berger A and others. ‘Tox-positive Corynebacterium ulcerans in hedgehogs, Germany’ Emerging Microbes and Infections 2019: volume 8, issue 1, pages 211 to 217

31. Katsukawa C and others. ‘Toxigenic Corynebacterium ulcerans isolated from a wild bird (ural owl) and its feed (shrew-moles): comparison of molecular types with human isolates’ BMC Research Notes 2016: volume 9, issue 1, pages 1 to 6

32. Thomas A and others. ‘Active circulation of Corynebacterium ulcerans among nonhuman primates’ Microbiology Spectrum 2022, pages e00894 to e00922

33. Busch A and others. ‘Genome sequence of a pathogenic Corynebacterium ulcerans strain isolated from a wild boar with necrotizing lymphadenitis’ BMC Research Notes 2019: volume 12, issue 1, pages 1 to 3

34. Katsukawa C and others. ‘Prevalence of Corynebacterium ulcerans in dogs in Osaka, Japan’ Journal of Medical Microbiology 2012: volume 61, issue 2, pages 266 to 273

35. Hacker E and others. ‘Corynebacterium ulcerans, an emerging human pathogen’ Future Microbiology 2016: volume 11, issue 9, pages 1,191 to 1,208

36. Meinel DM and others. ‘Next generation sequencing analysis of 9 Corynebacterium ulcerans isolates reveals zoonotic transmission and a novel putative diphtheria toxin-encoding pathogenicity island’ Genome Medicine 2014: volume 6, issue 11, pages 1 to 13

37. Meinel DM and others. ‘Zoonotic transmission of toxigenic Corynebacterium ulcerans strain, Germany, 2012’ Emerging Infectious Diseases 2015: volume 21, issue 2, page 356

38. Hogg R and others. ‘Possible zoonotic transmission of toxigenic Corynebacterium ulcerans from companion animals in a human case of fatal diphtheria’ The Veterinary Record 2009: volume 165, issue 23, page 691

39. Sykes JE and others. ‘Corynebacterium ulcerans bronchopneumonia in a dog’ Journal of Veterinary Internal Medicine 2010: volume 24, issue 4, pages 973 to 976

40. Berger A and others. ‘Toxigenic Corynebacterium ulcerans in woman and cat’ Emerging Infectious Diseases 2011: volume 17, issue 9, page 1,767

41. Vandentorren S and others. ‘Toxigenic Corynebacterium ulcerans in a fatal human case and her feline contacts, France, March 2014’ Eurosurveillance 2014: volume 19, issue 38, page 20,910

42. Kamada T and others. ‘Case of acute pharyngitis caused by Corynebacterium ulcerans in Ibaraki Prefecture’ Nihon Jibiinkoka Gakkai Kaiho 2012: volume 115, issue 7, pages 682 to 686

43. Lartigue M-Fdr and others. ‘Corynebacterium ulcerans in an immunocompromised patient with diphtheria and her dog’ Journal of Clinical Microbiology 2005: volume 43, issue 2, pages 999 to 1,001

44. Otsuji K and others. ‘The first fatal case of Corynebacterium ulcerans infection in Japan’ JMM case reports 2017: volume 4, issue 8

45. Yasuda I and others. ‘Severe pneumonia caused by toxigenic Corynebacterium ulcerans infection, Japan’ Emerging infectious diseases 2018: volume 24, issue 3, page 588

46. Wake K and others. ‘Transmission of toxigenic Corynebacterium ulcerans infection with airway obstruction from cats to a human’ Acute Medicine and Surgery 2021: volume 8, issue 1

47. Zendri F and others. ‘Case report: toxigenic Corynebacterium ulcerans diphtheria-like infection in a horse in the UK’ Frontiers in Veterinary Science 2021: volume 8, page 650238

Appendix 1. Draft IMT agenda

1. Welcome, introductions and apologies
2. Purpose of meeting
3. Minutes and actions from previous meetings (if applicable)
4. Update on situation to date
   • epidemiological
   • microbiological
   • environmental
5. Current risk assessment
6. Control measures
   • household
   • veterinary practice
   • other settings (human or animal)
7. Further investigations
   • epidemiological
   • microbiological
   • environmental
8. Communications
   • household
   • veterinary practice
   • public (if required)
9. Agreed actions
10. Any other business (AOB)
11. Next meeting

Appendix 2. Corynebacterium ulcerans (C. ulcerans) fact sheet: reducing the risk of diphtheria for people who have had contact with an infected animal

Corynebacterium ulcerans

Corynebacterium ulcerans (shortened to C. ulcerans) is a type of bacteria that can cause a disease called diphtheria. C. ulcerans can affect humans and animals. You are receiving this fact sheet because you are a close contact of an animal that has been diagnosed with toxigenic C. ulcerans.

Due to the success of a highly effective vaccination programme, it is uncommon to see diphtheria in the UK. The majority of cases acquired within the UK are mild infections in people who have not been fully vaccinated, or in older adults who have been fully vaccinated but their immunity has reduced. Although diphtheria can be a serious illness, there are effective treatments available including antibiotics. There are also steps that you can take to prevent yourself from catching diphtheria. These steps are included in this fact sheet.

Diphtheria

Diphtheria is a caused by a toxin (poison) made by bacteria. Corynebacterium diphtheriae and C. ulcerans are the 2 most common bacteria that can cause diphtheria. It can also be caused by Corynebacterium pseudotuberculosis, although this is very rare. If the infection is left untreated, it can be potentially life threatening.

Symptoms of diphtheria in humans

Symptoms usually begin 2 to 5 days after being in contact with the diphtheria bacteria. Symptoms will depend on the site of infection, but the most severe form of diphtheria affects the throat and tonsils. This is known as respiratory diphtheria.

The first symptoms are usually a sore throat, loss of appetite and a mild fever. Within 2 to 3 days, a membrane may form over the mouth and tonsils that can make it hard to swallow and breathe. The infection can also cause the lymph glands and tissues on both sides of the neck to swell (sometimes referred to as a ‘bull neck’).

The bacteria responsible for diphtheria can also cause small skin sores that form larger ulcers, which usually appear on exposed limbs, particularly the legs. This form of the disease is known as cutaneous diphtheria.

Presentation in animals

Animals infected with C. ulcerans can develop nasal congestion, streaming eyes and sneezing. C. ulcerans bacteria can also cause skin lesions, ulcers or abscesses in animals. You should consult a private veterinary surgeon if your pet develops any unexplained skin wounds or lumps.

Spread of diphtheria

C. ulcerans bacteria can live in the mouth, throat, nose or skin of people or animals with the infection. While very uncommon, there have been cases of pets with C. ulcerans passing the infection on to humans. The bacteria may spread when a person or animal comes into contact with droplets in the air after an infected person or animal has coughed or sneezed. Less frequently, the infection may also spread following close contact with undressed skin lesions, or while providing wound care or other care (for example, grooming an animal or changing its bedding).

C. ulcerans infection has also been found in a wide range of other, non-domestic, animals. The infection may spread from farm animals to humans, from animals to vets treating those animals, or from people drinking unpasteurised milk or other unpasteurised dairy products.

Animals may also be able to pass the bacteria to each other by sharing food or water bowls, toys or bedding.

Diphtheria vaccination

If your local health protection team advises that you are considered to be a close contact of an animal with C. ulcerans you will be advised to get in touch with your GP to check your vaccination status. If you have not been vaccinated against diphtheria you will be offered a full course of the vaccination. If you have been vaccinated previously, but this was more than 12 months ago, you will be offered a booster dose to boost your immunity against infection.

Diphtheria vaccination protects against the disease in humans and is very effective. It gives protection against disease by producing antibodies to the diphtheria toxin. The vaccine prompts the body to produce antibodies against the diphtheria toxin so that if the person comes into contact with diphtheria later in life, the body’s immune system will be able to protect itself.

Diphtheria vaccination is given as part of the UK’s primary immunisation programme. All infants should receive the primary immunisation course of 3 doses of a diphtheria-containing vaccine in the first year, usually given at 8, 12 or 16 weeks of age. Children should receive a first booster dose between 3.5 and 5 years of age and a second booster dose between 13 and 18 years of age.

Diagnosis

In humans and animals, diagnosis is based on clinical examination and the testing of swabs, usually taken from the throat but also sometimes from sores in the case of cutaneous diphtheria. Special laboratory tests are needed to detect the toxin and confirm the diagnosis.

Follow-up of human contacts

It is not usually recommended that human close contacts of animals with C. ulcerans are treated with antibiotics, although there are exceptions to this. This is because the risk of the bacteria being passed on to a person is low. Antibiotics can also have some side effects, and should only be given if absolutely necessary.

You will be offered a swab to test for diphtheria infection, as you may still catch the infection even if you have been fully vaccinated. The diphtheria vaccine doesn’t stop you from catching the infection, but will help to stop you from developing symptoms of diphtheria.

You should closely monitor yourself and members of your family for the symptoms of diphtheria in humans outlined in this information sheet for at least 10 days after your pets have completed their antibiotic treatment. If you do not own the affected animal but were advised by your health protection team that you are considered to be a close contact, you should monitor yourself for symptoms for 10 days after your last contact with the animal. If you do develop any symptoms, you should get in touch with your GP. It may be helpful to have this information sheet to hand when you talk to your GP.

Treatment of animals with C. ulcerans infection

If your pet is diagnosed with C. ulcerans, your vet is likely to prescribe antibiotics. They will usually advise that your pet is swabbed again a few days after completing the antibiotics to ensure they have cleared the infection. You may also be advised to treat any other animals in the household with antibiotics at the same time and to have the animals swabbed together when they have completed the course. This will reduce the chance that the animals will re-infect each other, and potentially be able to pass the bacteria on to you or a member of your family.

Like almost all diseases and injuries your pet may suffer, it is your responsibility as the owner to manage the C. ulcerans infection. Investigation, including swabbing, and treatment is unlikely to be covered by your pet insurance policy therefore it is likely that you will have to pay for any costs.

What you need to do while your pet is being treated for C. ulcerans infection

Your vet will advise you on how to care for your pet. This may include instructions for wound care if your pet has a skin lesion or abscess. If possible, you should wear disposable gloves while caring for your pet’s wound, and wash your hands thoroughly afterwards. You should also wash your hands thoroughly with soap and water after handling your pet, their food or water bowl, bedding and toys.

When your pet has completed their course of antibiotics, their bedding, bowls and toys should be thoroughly washed; it is recommended that they are hot washed in water over 60°C.

If it is not possible to wash your pet’s bedding, you may consider replacing it when your pet’s antibiotic treatment is complete.

If your pet often sits on the sofa or bed, you should discourage them from doing so until they have completed their course of antibiotics. If this is difficult to enforce, ensure you wash any bedding or sofa covers regularly whilst your pet is being treated or put an extra blanket on the sofa or bed for them to sleep on which is separate from your bedding and easier to wash.

You should prevent your pet from licking other animals or people. While it may be difficult to keep animals in the same household apart, keep your pet away from animals outside the household until your vet advises that they have cleared the infection. You can still take your pet for a walk, but try to avoid direct contact between your pet and other animals and humans when out walking until the antibiotic course is complete. When picking up your pets faeces, try to wear gloves when doing so.

You do not need to avoid having guests at your house, but ideally, avoid letting your pet have contact with anyone from outside your household until they have cleared the infection. If someone does come to the house and has minimal contact with your pet (for example, sitting in the same room as your pet, or stroking your pet) they would not be considered to be a close contact of the animal.

Unless you have been identified as working in a high-risk occupation, it is not necessary for you to stay off work or school if you are completely well. If you develop any of the symptoms of diphtheria in humans described in this information sheet, you should stay off work or school and get in touch with your GP.

Management of diphtheria in humans

The risk of developing diphtheria following contact with an animal infected with C. ulcerans is low. However, if you are diagnosed with diphtheria, a doctor will prescribe you a course of antibiotics, and particularly in cases of severe respiratory diphtheria they will also advise other medicines (such as anti-toxin) to stop the effects of toxins produced by the bacteria.

Additional information about diphtheria can be found on the NHS website.

Appendix 3. Template email to veterinary practices

This email template may not be required in all incidents. If indicated, it can be shared with veterinary colleagues to summarise key public health actions for animals and their human contacts.

Re: [animal’s name]; [type of animal]; owned by [owner’s name] of [owner’s address]

Dear [colleague]

I am writing regarding the recent diagnosis of [animal’s name] with Corynebacterium ulcerans infection. As you will be aware, C. ulcerans was isolated from a recent sample from [site of sample]. As there is a low risk of transmission of C. ulcerans to humans from an animal index case, some public health follow-up is required for the close human contacts of [animal’s name].

Actions for [animal’s name]

You may already have given the owners of [animal’s name] advice regarding antibiotic treatment and clearance swabbing. We would be grateful if you could also consider coordinated treatment and clearance swabbing of any other household pets if appropriate. There are no funds available for this, so the cost of treating and swabbing additional pets would need to be met by the owners.

To confirm clearance of toxigenic C. ulcerans, repeat swabs should ideally be taken at least 5 to 7 days following completion of the antibiotic course. If the animal remains positive on repeat swabs, the Animal and Plant Health Agency (APHA) will be able to advise on further management.

We will advise the owners to wash pet bowls, toys and bedding when all household pets receiving treatment have completed their course of antibiotics. We would be grateful if you could re-enforce this advice.

Actions for human contacts

A close human contact is usually considered to be someone who regularly handles or cares for the animal (for example, an owner who lives in the same household and has close contact such as grooming, wound care or changing bedding).

However, a member of veterinary staff may also be considered a close contact if they cared for the animal (for example have provided wound care) without personal protective equipment (PPE: gloves, apron, surgical mask). Any possible veterinary contacts should be discussed with the health protection team (HPT), who can assist in risk assessing if the member of staff should be followed up as a contact.

If the HPT agrees a member of staff is a contact, the same actions should be taken as the owner and other close human contacts of the animal.

These actions include:

• the member of staff should receive written and verbal ‘warn and inform’ advice, and should self-monitor for symptoms for 10 days since their last contact with the animal; if they develop symptoms (including sore throat, fever, loss of appetite) they should discuss urgently with occupational health if appropriate, or with their own GP
• chemoprophylaxis is not routinely recommended for human contacts unless the exposure was particularly high risk (the health protection team or incident management team should be able to advise)
• the member of staff only needs to be excluded if they have symptoms or had a particularly high-risk exposure
• the member of staff should have nasopharyngeal and throat swabs, and skin swabs if they have an open wound or skin lesion
• the member of staff’s immunisation status should be checked; if they have not completed a primary immunisation schedule for a diphtheria-containing vaccine, this should be completed; if they have completed the primary schedule, they should be offered a booster; if the primary schedule or a booster has been received in the last 12 months, no further action is needed

If you have any questions, contact your local health protection team.

Appendix 4. Epidemiology of toxigenic C. ulcerans human and animal cases in England, 2009 to 2021

Note that cases are based on the date of onset of symptoms.

Table 5a. Toxigenic C. ulcerans cases (human index)

Year	N [note 1]	Positive contacts: animal	Positive contacts: human
2009	2	0	0
2010	1	0	0
2011	2	0	0
2012	1	0	0
2013	0	0	0
2014	1	1	0
2015	3	0	0
2016	2	1	0
2017	1	0	0
2018	3	0	0
2019	8	1	2
2020	1	0	0
2021	7	2	0
Total	32	5	2

[note 1] One individual with a positive laboratory isolate in 2019 also had 2 further positive isolates in 2021, not displayed in these tables.

Table 4b. Toxigenic C. ulcerans cases (animal index)

Year	N	Positive contacts: animal	Positive contacts: human
2009	-	-	-
2010	-	-	-
2011	-	-	-
2012	-	-	-
2013	-	-	-
2014	-	-	-
2015	-	-	-
2016	-	-	-
2017	1	0	0
2018	2	0	0
2019	7	0	0
2020	2	0	0
2021	2	0	0
Total	14	0	0

1. Laboratory identification and confirmation of diphtheria: Isolation of diphtheria toxin-producing corynebacteria (indicated by PCR detection of toxin gene and confirmed by Elek test) from a clinical specimen by a reference laboratory. ↩ ↩²