Diphtheria in England: 2022
Updated 23 May 2023
Applies to England
© Crown copyright 2023
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This report summarises the epidemiology of diphtheria in England for 2022 and reiterates current recommendations on diagnosis and clinical management of diphtheria.
Main messages
Diphtheria is a vaccine-preventable disease that can be life-threatening.
From January to December 2022, toxigenic corynebacteria was isolated from 87 human individuals in England. Of these 87 cases, there were:
- 76 Corynebacterium diphtheriae (C. diphtheriae) cases (including 72 among asylum seekers with recent arrival in England and 4 travel-acquired cases)
- 11 Corynebacterium ulcerans (C. ulcerans) cases
- 1 non-toxigenic tox gene-bearing (NTTB) case of C. diphtheriae
There were 3 deaths, 2 of whom were confirmed with toxigenic C. ulcerans and 1 asylum-seeking individual with toxigenic C. diphtheriae detected from a throat swab.
There were 72 cases of toxigenic C. diphtheriae among asylum seekers with recent arrival in England and 1 probable case clinically compatible with diphtheria but for whom toxigenic C. diphtheriae was not isolated. Of these 72 cases:
- 36 cases had cutaneous symptoms
- 3 cases had severe respiratory diphtheria
- 10 cases had mild respiratory symptoms
- 2 cases had both cutaneous and respiratory symptoms
- 2 cases had other presentation
- 20 cases were respiratory carriers
Of the 4 travel-acquired cases of toxigenic C. diphtheriae, 3 presented with cutaneous symptoms while the fourth was an asymptomatic carrier in the same household as 2 of the cases.
5 of the 11 toxigenic C. ulcerans cases presented with cutaneous symptoms, 1 case had classical respiratory diphtheria with a membrane and 4 were asymptomatic respiratory carriers. The remaining case had toxigenic C. ulcerans isolated from pleural fluid with an atypical presentation.
There was 1 NTTB C. diphtheriae case who presented with mild respiratory symptoms.
All the toxigenic C. ulcerans cases were linked to companion animals.
Background
Diphtheria is a very rare infection in England due to the success of the routine immunisation programme that was introduced in 1942, when the average annual number of cases was about 60,000 with 4,000 deaths (1). Over the past decade, the number of diphtheria cases in England has increased from an average of 2 to more than 10 cases per year (with the exception of 2020).
Diphtheria vaccine is an inactivated toxoid vaccine available as a combination vaccine that is highly effective in protecting individuals from the effects of toxin-producing corynebacteria.
The 3 Corynebacterium species that can potentially produce toxin are:
- C. diphtheriae
- C. ulcerans
- Corynebacterium pseudotuberculosis (C. pseudotuberculosis)
C. diphtheriae is associated with person-to-person spread via respiratory droplets and close contact. C. ulcerans and C. pseudotuberculosis are both less common globally and are traditionally associated with farm animal contact and dairy products and, more recently, for C. ulcerans, with companion animals. (2, 3)
Although there is no direct evidence of person-to-person transmission of C. ulcerans infection, there have been incidents that suggest this mode of transmission is possible (3) and therefore contact tracing is carried out as for cases of toxigenic C. diphtheriae.
Diphtheria can present with a range of clinical presentations. Classic respiratory diphtheria is characterised by a swollen ‘bull neck’ and strongly adherent pseudomembrane which obstructs the airways; a milder respiratory form of the disease where patients present with sore throat or pharyngitis can occur in immunised or partially immunised individuals (2).
Cutaneous presentations, characterised by ‘rolled edge’ ulcers, are also common, particularly in tropical regions (3).
Treatment involves prompt administration of diphtheria anti-toxin (DAT) for severe cases to prevent the late complications from circulating toxin and appropriate antibiotics for clearance of the organism from the nasopharynx. Public health management of clinical cases of diphtheria in England is provided by local Health Protection Teams (HPTs), including identification, assessment and prophylaxis of close contacts.
Laboratory confirmation of diphtheria is usually made by detection of the expression of diphtheria toxin in isolates of C. diphtheriae, C. ulcerans or C. pseudotuberculosis or initially by detection of DNA from these species together with the toxin gene, using PCR.
The determination of toxigenicity in England requires submission of isolates of these 3 species to UK Health Security Agency’s (UKHSA) Vaccine Preventable Bacteria section (VPBS), Respiratory and Vaccine Preventable Bacteria Reference Unit (RVPBRU), which is the National Reference Laboratory (NRL) for diphtheria. Identification and the presence of the toxin (tox) gene are tested for by real-time PCR. If the tox gene is detected, the isolate is tested for expression of diphtheria toxin using the Elek test (4). Public health actions proceed on the basis of the results from PCR testing.
The availability of both PCR and Elek testing has identified a number of C. diphtheriae isolates carrying the tox gene (PCR-positive) but not expressing the toxin (Elek-negative), termed non-toxigenic tox gene-bearing (NTTB) strains (3). The pathogenesis and clinical significance of isolation of this organism are not yet well understood; NTTB are not thought to cause diphtheria and therefore, as reversion to toxin expression is considered highly unlikely, updated guidelines recommend such cases are managed as non-toxigenic strains with antibiotic therapy only if clinically indicated.
Cases of diphtheria in England in 2022
This 2022 review updates a previous annual review of diphtheria cases in England for 2021 (5). Data sources for the enhanced surveillance of diphtheria include notifications, reference and NHS laboratory reports, death registrations, and individual case details such as vaccination history, source of infection, and severity of disease obtained from hospital records and general practitioners.
During 2022, toxigenic strains of corynebacteria were identified from 87 persons by the NRL. This compares with 10 toxigenic strains in 2021 (7 C. ulcerans; 3 C. diphtheriae), 1 toxigenic strain in 2020 (C. ulcerans), 10 toxigenic strains in 2019 (all C. ulcerans) and 11 toxigenic strains in 2018 (3 C. ulcerans; 8 C. diphtheriae). One NTTB C. diphtheriae strain was also identified during the 2022 period, 1 in 2021 and 2 in each of the years 2020, 2019 and 2018.
Diphtheria is a notifiable disease in accordance with the amended Public Health (Control of Disease) Act 1984 and accompanying regulations (6). Suspected cases are reported to UKHSA via the Notifications of Infectious Diseases (NOIDs) system by registered medical practitioners based on clinical suspicion; or by local microbiology laboratories via the Second-Generation Surveillance System (SGSS) on identification of a notifiable organism.
In 2022, there were 22 diphtheria notifications received from NOIDs for England; laboratory investigation identified:
- 3 notifications as toxigenic C. diphtheriae infections
- 8 notifications as non-toxigenic C. diphtheriae infections
The 11 remaining notifications were submitted presumptively in the absence of identification of corynebacteria by local testing and were subsequently found to not be a corynebacterial infection. All toxigenic cases were formally notified to UKHSA via SGSS or through direct referral of isolates to the NRL.
During 2022, the NRL received a total of 253 isolates for confirmation and toxigenicity testing from 242 individual cases for investigation (45 human and 5 animals) from England. This compares with 50 isolates (45 human and 5 animals) in 2021, 29 isolates (25 human and 4 animals) in 2020, and 101 isolates (96 human and 5 animal) in 2019.
Eighty one Isolates from 76 individuals were identified as toxigenic C. diphtheriae and 14 isolates from 11 individuals as toxigenic C. ulcerans, only 3 of which were formally notified (Table 1). Toxigenic C. ulcerans strains were confirmed from a further 20 isolates (from 18 companion animals), 15 of which were not epidemiologically linked to a human case.
Of the remaining isolates, 106 were non-toxigenic C. diphtheriae, 17 were non-toxigenic C. ulcerans and 14 were not C. diphtheriae, C. ulcerans, or C. pseudotuberculosis. One NTTB C. diphtheriae was also isolated.
Table 1. Summary of (a) Diphtheria notifications (NOIDs) (b) Toxigenic corynebacteria by strain and (c) NRL toxigenicity testing, England: 2022
| (a) Total diphtheria notifications in 2022 | |
|---|---|
| Number due to toxigenic C. diphtheriae | 3 |
| Number due to toxigenic C. ulcerans | 0 |
| Number due to non-toxigenic tox gene bearing (NTTB) C. diphtheriae | 0 |
| Number due to non-toxigenic C. diphtheriae | 8 |
| Notified but did not meet possible case classification | 11 |
| (b) All toxigenic corynebacteria isolates from human cases in 2022 | |
|---|---|
| Toxigenic C. diphtheriae [note 1] | 81 |
| Toxigenic C. ulcerans [note 2] | 14 |
| NTTB C. diphtheriae | 1 |
| (c) All toxigenic corynebacteria isolates from human cases in 2022 | |
|---|---|
| Toxigenic C. diphtheriae | 81 |
| NTTB C. diphtheriae | 1 |
| Non-toxigenic C. diphtheriae | 106 |
| Toxigenic C. ulcerans [note 3] | 34 |
| Non-toxigenic C. ulcerans [note 4] | 17 |
| Other – Not C. diphtheriae, C. ulcerans, or C. pseudotuberclerosis [note 5] | 14 |
[note 1] Includes multiple isolates from 4 individuals
[note 2] Includes multiple isolates from 3 individuals
[note 3] Includes 20 isolates from 18 companion animals, 15 not epidemiologically linked to a human case
[note 4] Includes 9 isolates from companion animals
[note 5] Includes 1 isolate from a companion animal
Toxigenic Corynebacterium diphtheriae
In 2022, toxigenic C. diphtheriae strains from 76 individuals were identified in England, including 4 cases among residents in England and 72 cases among asylum-seeking individuals with recent arrival in England (presented separately below).
The 4 cases among residents in England had an age range of 10 to 60 years. Of these, 3 cases were among fully vaccinated individuals in the same household, aged under 15 years, with recent travel to Sri Lanka. Two cases presented with infected bites on the lower limbs; contact tracing identified a further asymptomatic case in a family member.
Toxigenic C. diphtheriae was isolated from a wound swab in a fourth individual, usually resident in the Gambia. The case was male, aged 60 years, and of unknown vaccination status. The case sustained an injury to the hand and was hospitalised for 2 days with low grade fever; DAT was not indicated.
Initial contact tracing for the 4 cases identified 8 close contacts. Seven contacts were offered antibiotic prophylaxis and vaccinations (as necessary); 1 contact was not in England. Due to the ongoing adherence to coronavirus (COVID-19) protocols, the use of personal protective equipment (PPE) was deemed sufficiently protective against the transmission of C. diphtheriae and C. ulcerans; no breaches in PPE use were reported among healthcare workers in contact with the cases and therefore none were considered to be close contacts.
One NTTB C. diphtheriae isolate was identified in 2022 from an individual with mild respiratory symptoms. The case was a fully vaccinated male, aged in their twenties, with no history of recent travel. Contact tracing identified 3 close contacts; all were offered antibiotic prophylaxis and vaccinations.
Toxigenic Corynebacterium diphtheriae in asylum seekers
During 2022, an outbreak of diphtheria was reported among migrants in Europe (7) with a similar increase in cases identified among individuals arriving by small boat to England (8).
Toxigenic C. diphtheriae was isolated from 72 asylum-seeking individuals in England; an additional probable case (clinically compatible with diphtheria but for whom toxigenic C. diphtheriae was not isolated) was also identified. Cases were predominantly young males with a median age of 17 years (range 2 to 41 years), with no (or unknown) vaccination history.
The majority of cases have presented with cutaneous skin lesions or wounds acquired during extensive travel en route to the UK thus prompting clinical assessment and screening for corynebacteria. There were 35 cases with toxigenic C. diphtheriae isolated from wound swabs. Not all cases presenting with wounds had subsequent isolation of C. diphtheriae, with other organisms (such as Group A Streptococcus and Staphylococcus aureus) also commonly isolated from these sites.
There were 2 severe cases of respiratory diphtheria. Both cases had classical diphtheria, presenting with sore throat, pseudomembrane and fever, and requiring hospitalisation and treatment with DAT. Contact tracing from 1 of the cases identified a further 2 individuals (1 respiratory case and 1 asymptomatic carrier) with toxigenic C. diphtheriae isolated from throat swabs.
There was 1 fatality in an individual from whom the detection of DNA from C. diphtheriae and the diphtheria toxin gene was confirmed by PCR from a throat swab. However, the cause of death is subject to a coroner’s inquest, which has yet to take place.
There were 30 confirmed cases with toxigenic C. diphtheriae isolated from nose and/or throat samples. Of these cases:
- 10 cases reported mild respiratory symptoms (including sore throat, cough and/or swollen glands)
- 20 cases reported no (or unknown) associated respiratory symptoms
Of note, 11 cases with respiratory carriage reported skin lesions or wounds, but C. diphtheriae was not isolated from these sites.
There were 2 cases with both respiratory and cutaneous presentation and 2 cases with other presentations (toxigenic C. diphtheriae was isolated from a urethral swab and a penile skin swab, but with no lesions or significant wounds noted).
In response to the increase in cases, supplementary guidance was developed to support management of cases in asylum seeker accommodation settings in England as part of an Enhanced National Incident response. In addition, mass antibiotic prophylaxis and vaccination have been recommended for all individuals resident in, or previously resident in, initial reception centres where significant barriers to individual targeted case and contact management have been identified (such as challenges with contact tracing, testing and prophylaxis). This mass intervention has been recommended to continue until October 2023 with planned regular review in the interim.
Toxigenic Corynebacterium ulcerans
There were 14 toxigenic C. ulcerans isolates from 11 individuals identified in 2022, of which 5 had a cutaneous presentation (including 1 with secondary isolation from a throat swab), 1 had classical respiratory diphtheria (with pseudomembrane), 4 were asymptomatic carriers, and 1 had toxigenic C. ulcerans isolated from pleural fluid with an atypical presentation. Of the cases, 8 were men and the age range was 22 to 81 years.
Only 5 cases had a recorded history of receiving diphtheria-containing vaccines, of which 4 were fully vaccinated. Five cases were hospitalised and 1 case was treated with DAT. There were 2 fatalities, in individuals aged over 60, and 80 years, respectively. All cases had contact with domestic pets, and swabs were taken from the animal contacts of 10 cases. In total, swabs were taken from 12 companion animals and 3 of these swabs tested positive for C. ulcerans (2 of which were from animals in the same household).
Toxigenic C. ulcerans was isolated from a non-healing diabetic ulcer on 2 occasions in the same individual in 2022. The case was male, aged in their sixties, with unknown vaccine history and contact with 2 pet dogs each testing positive during respective episodes. The second course of treatment for both the human and animal contacts was coordinated due to suspected recolonisation from the animals (or an environmental source) as the factor for the repeat episode.
Four further cutaneous cases of C. ulcerans were reported, with contact tracing identifying 1 additional asymptomatic carrier among close contacts. All individuals were aged over 60 years, with unknown vaccination history, and 4 were male. All had contact with cats and/or dogs in the household, of which swabs from only 1 dog were positive for toxigenic C. ulcerans.
There were 2 fatalities: 1 case was admitted to hospital with necrotising fasciitis and died 3 days after admission; the other case had a history of respiratory issues, required emergency intubation, and died 7 days after admission due to pneumonia and sepsis.
There was 1 case of classical respiratory diphtheria requiring admission to the ITU and treatment with DAT. The case was male, aged in their seventies, and only partially vaccinated. He had contact with 2 dogs in the household; no swabs were taken for the animals.
The remaining case was admitted to hospital with breathing difficulties and toxigenic C. ulcerans was subsequently isolated from pleural fluid. The case was a fully vaccinated female, in their fifties. Contact tracing identified 3 asymptomatic carriers in the household, aged between 22 and 62 years and all fully vaccinated. The cases had contact with 2 dogs in the household; both tested negative for C. ulcerans.
Contact tracing from all toxigenic C. ulcerans cases identified 45 close contacts including 12 household contacts, 5 non-household contacts, and 28 health care workers. All contacts were swabbed, offered chemoprophylaxis and vaccination (where appropriate).
Due to the ongoing adherence to COVID-19 protocols, the use of personal protective equipment (PPE), was deemed sufficiently protective against the transmission of C. diphtheriae and C. ulcerans; no breaches in protocol were reported by the other health care workers in contact with the cases and therefore they were not considered as close contacts.
Table 2. Clinical presentation of diphtheria cases and causative organism, England 2022
| Clinical presentation of cases | Toxigenic C. diphtheriae | Toxigenic C. ulcerans | NTTB C. diphtheriae | Total |
|---|---|---|---|---|
| Severe respiratory diphtheria (sore throat with exudate or membrane) | 3 | 1 | – | 4 |
| Mild respiratory diphtheria (sore throat/pharyngitis) | 10 | – | 1 | 11 |
| Cutaneous diphtheria | 39 [note 6] | 4 | – | 43 |
| Cutaneous and respiratory diphtheria | 2 | 1 | – | 3 |
| Asymptomatic/respiratory carrier | 21 | 4 | – | 25 |
| Other | 2 | 1 | – | 3 |
[note 6] Includes 1 probable case clinically compatible with diphtheria but from whom C. diphtheriae was not isolated at local testing.
Further information
Microbiological laboratories are requested to promptly submit all suspect isolates of C. diphtheriae, C. ulcerans and C. pseudotuberculosis to the NRL at UKHSA, RVPBRU, Colindale, London using the laboratory request form R3.
From 1 April 2014, the test result which helps inform public health actions is a real-time PCR result which confirms the identity of C. diphtheriae, C. ulcerans or C. pseudotuberculosis and determines whether the gene for the diphtheria toxin (tox) is present.
If the tox gene is detected, the isolate goes on to have an Elek test to confirm expression of toxin (4). The NRL also provides advice on all aspects of laboratory testing for diphtheria and related infections. Advice on immunisation against diphtheria, provision of vaccine and provision of DAT for therapeutic use is available from the UKHSA Colindale Immunisation and Vaccine Preventable Diseases Division and in the recently published revised guidance for public health control and management of diphtheria.
As a disease becomes rare, the completeness and accuracy of surveillance information become more important and each clinical diagnosis (that is, notification) needs to be confirmed by laboratory diagnosis. In addition to notifications, enhanced surveillance for diphtheria incorporates data from reference and NHS laboratories, death registration, and individual case details such as vaccination history, source of infection and severity of disease obtained from hospital records, general practitioners and local incident team reports.
Linkage of notified cases of suspected diphtheria and confirmatory laboratory data shows that most notifications are cases of pharyngitis associated with isolation of non-toxigenic strains of C. diphtheriae, and therefore interpretation of notification data should be undertaken with caution.
References
1. UKHSA. ‘Diphtheria: the green book, chapter 15’
2. Wagner KS, White JM, Crowcroft NS, De Martin S, Mann G, Efstratiou A (2010). ‘Diphtheria in the United Kingdom, 1986-2008: the increasing role of Corynebacterium ulcerans’. Epidemiology and Infection: volume 138, issue 11, pages 1519-1530
3. UKHSA (2022). ‘Public health control and management of diphtheria in England: 2022 guidelines’
4. De Zoysa A, Efstratiou A, Mann G, Harrison TG, Fry NK (2016). ‘Development, validation and implementation of a quadruplex real-time PCR assay for identification of potentially toxigenic corynebacteria’. Journal of Medical Microbiology: volume 65, issue 12, pages 1521-1527
5. UKHSA (2022). ‘Diphtheria in England: 2021’. Health Protection Report: volume 16 number 5
6. UKHSA (2021). ‘Notifiable diseases and causative organisms: how to report’
7. European Centre for Disease Prevention and Control (October 2022). ‘Increase of reported diphtheria cases among migrants in Europe due to Corynebacterium diphtheriae, 2022’.
8. UKHSA (2022). ‘Diphtheria: cases among asylum seekers in England, health protection report (data to 25 November 2022)’