Diphtheria in England: 2023
Updated 29 August 2024
Applies to England
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This report summarises the epidemiology of diphtheria in England for 2023 and reiterates current recommendations on diagnosis and clinical management of diphtheria.
Main messages
The main points arising from this report are that:
- diphtheria is a vaccine-preventable disease that can be life-threatening
- from January to December 2023, toxigenic corynebacteria were isolated from 27 human individuals in England
- of these 27, 16 were Corynebacterium diphtheriae cases (including 13 among asylum seekers with recent arrival in England and 3 travel-acquired cases) and 11 were C. ulcerans cases
- there were zero deaths
- of the 13 C. diphtheriae cases among asylum seekers, 6 had cutaneous symptoms, 3 had mild respiratory symptoms and 3 had both cutaneous and respiratory symptoms (the remaining one case was a respiratory carrier)
- all of the 3 travel-acquired cases of toxigenic C. diphtheriae cases presented with cutaneous symptoms
- 9 of the 11 toxigenic C. ulcerans cases presented with cutaneous symptoms (one case had an infected joint bursa while the remaining case presented with a rash and fatigue)
- there were no non-toxigenic tox gene-bearing (NTTB) cases, compared to one last year
- there were no cases presenting with classical respiratory diphtheria with membrane
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 are 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 (3).
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 three 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 (3).
Cases of diphtheria in England in 2023
This 2023 review updates a previous annual review of diphtheria cases in England for 2022 (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 2023, 40 toxigenic strains of corynebacteria were identified from 27 persons by the NRL. This compares with toxigenic strains identified from 87 persons in 2022 (76 C. diphtheriae, of which 72 were among asylum seekers with recent arrival in England; 11 C. ulcerans), 10 toxigenic strains in 2021 (7 C. ulcerans; 3 C. diphtheriae), one 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). No NTTB C. diphtheriae strains were identified during the 2023 period, compared to one in both 2022 and 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 2023, there were 33 diphtheria notifications received from NOIDs for England. Laboratory investigation identified:
- 2 notifications as toxigenic C. diphtheriae infections
- 15 notifications as non-toxigenic C. diphtheriae infections
The 16 remaining notifications were submitted presumptively in the absence of identification of corynebacteria by local testing. Ten were subsequently found not to be a corynebacterial infection, and one was not tested after being deemed clinically incompatible with diphtheria. Both toxigenic cases were formally notified to UKHSA through direct referral of isolates to the NRL.
During 2023, the NRL received a total of 328 isolates for confirmation and toxigenicity testing from 278 individual cases for investigation (170 human and 108 animals) from England. This compares with 253 isolates from 242 individual cases (202 human and 40 animals) in 2022, 50 individual isolates (45 human and 5 animals) in 2021 and 29 individual isolates (25 human and 4 animal) in 2020.
Fourteen isolates from 11 individuals were identified as toxigenic C. ulcerans and 26 isolates from 16 individuals as toxigenic C. diphtheriae, only 2 of which were formally notified (Table 1). Toxigenic C. ulcerans strains were confirmed from a further 48 isolates from 40 animals, one of which was epidemiologically linked to a human case.
Of the remaining isolates, 116 were non-toxigenic C. diphtheriae, 68 were non-toxigenic C. ulcerans, 3 were non-toxigenic C. pseudotuberculosis, and 53 were not C. diphtheriae, C. ulcerans, or C. pseudotuberculosis.
Table 1. Summary of (a) Diphtheria notifications (NOIDs) (b) Toxigenic corynebacteria by strain and (c) NRL toxigenicity testing, England: 2023
| (a) Total diphtheria notifications in 2023 | |
|---|---|
| Number due to toxigenic C. diphtheriae | 2 |
| Number due to toxigenic C. ulcerans | 0 |
| Number due to non-toxigenic C. diphtheriae | 15 |
| Notified but did not meet possible case classification | 16 |
| (b) All toxigenic corynebacteria isolates from human cases in 2023 | |
|---|---|
| Toxigenic C. diphtheriae [note 1] | 26 |
| Toxigenic C. ulcerans [note 2] | 14 |
| NTTB C. diphtheriae | 0 |
| (c) All toxigenic corynebacteria isolates from human cases in 2023 | |
|---|---|
| Toxigenic C. diphtheriae | 26 |
| NTTB C. diphtheriae | 0 |
| Non-toxigenic C. diphtheriae | 116 |
| Toxigenic C. ulcerans [note 3] | 62 |
| Non-toxigenic C. ulcerans [note 4] | 68 |
| Non-toxigenic C. pseudotuberclerosis [note 5] | 3 |
| Other – Not C. diphtheriae, C. ulcerans, or C. pseudotuberclerosis [note 6] | 53 |
Note 1. Includes multiple isolates from 5 individuals
Note 2. Includes multiple isolates from 3 individuals
Note 3. Includes 48 isolates from 40 animals
Note 4. Includes 53 isolates from 47 animals
Note 5. Includes 1 isolate from an animal
Note 6. Includes 6 isolate from animals
Toxigenic Corynebacterium diphtheriae
In 2023, toxigenic C. diphtheriae strains from 16 individuals were identified in England, including 3 cases among residents in England and 13 cases among asylum-seeking individuals with recent arrival in England (presented separately below).
The 3 cases among residents in England had an age range of 24 to 49 years. Two of the cases were among individuals with recent travel to Sri Lanka (not epidemiologically linked) and the third had recent travel to Somalia. All 3 had unknown immunisation history. One of the cases had potential onset in Sri Lanka and was referred to the International Health Regulations National Focal Point for international contact tracing.
Initial contact tracing for the 3 cases identified 11 close contacts, 2 of which were healthcare workers (HCWs) whose personal protective equipment (PPE) was deemed insufficient. One of the cases was lost to follow up so contact tracing outside of the healthcare setting was not possible. All identified close contacts were offered antibiotic prophylaxis and vaccinations (as necessary). HCWs were individually risk assessed and excluded from work until negative diphtheria test results were obtained, as appropriate. Two of the contacts were children and were excluded from school until negative diphtheria test results were obtained.
Toxigenic Corynebacterium diphtheriae in asylum seekers
In 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). This continued into 2023, though there was a marked decrease in cases.
Toxigenic C. diphtheriae was isolated from 13 asylum-seeking individuals in England. Cases were predominantly young males (range 13 to 36 years), with no (or unknown) vaccination history.
The majority of cases 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 9 cases with toxigenic C. diphtheriae isolated from wound swabs, 4 of whom also presented with respiratory carriage. 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 no cases of severe respiratory diphtheria, and no fatalities.
There were 8 confirmed cases with toxigenic C. diphtheriae isolated from nose and/or throat samples. Of these cases, 5 reported mild respiratory symptoms (including sore throat, cough and/or swollen glands) and 3 cases reported no (or unknown) associated respiratory symptoms.
There were 4 cases with both respiratory and cutaneous presentation.
In response to the increase in cases in 2022, 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 were recommended for all individuals residing in, or previously residing in, initial reception centres. These recommendations continued until a review in October 2023, following which asylum seekers who arrived in the UK were offered a diphtheria vaccination as soon as possible with early testing, treatment, and isolation of cases continuing. The supplementary guidance was updated to reflect this (9).
Toxigenic Corynebacterium ulcerans
There were 14 toxigenic C. ulcerans isolates from 11 individuals identified in 2023, of which 9 had a cutaneous presentation, 1 had an infected joint bursa, and 1 had a sore throat and rash (with isolation from a throat swab). The age range for these cases was 7 to 89 years.
Six of the cases were hospitalised, though one of these hospitalisations was due to an unrelated injury. No cases were treated with DAT, and there were no fatalities. All but one of the individuals were recorded to have contact with animals, though only one of the animal contacts tested positive for C. ulcerans. Four cases were known to have had some diphtheria containing vaccine throughout their lives, though vaccination history for all was incomplete.
Contact tracing for all cases was carried out, with all identified close contacts being offered antibiotic prophylaxis and vaccinations (as necessary). A total of 30 HCWs were identified as close contacts as they were deemed to be wearing insufficient PPE. HCW close contacts were risk assessed individually and excluded from work until a negative diphtheria test was returned, as appropriate. All were offered antibiotic prophylaxis and a dose of diphtheria containing vaccine.
Table 2. Clinical presentation of diphtheria cases and causative organism, England 2022
| Clinical presentation of cases | Toxigenic C. diphtheriae | Toxigenic C. ulcerans | Total |
|---|---|---|---|
| Severe respiratory diphtheria (sore throat with exudate or membrane) | – | – | 0 |
| Mild respiratory diphtheria (sore throat/pharyngitis) | 3 | – | 3 |
| Cutaneous diphtheria | 9 | 9 | 18 |
| Cutaneous and respiratory diphtheria | 3 | – | 3 |
| Asymptomatic/respiratory carrier | 1 | – | 1 |
| Other | – | 1 | 1 |
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 (10).
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 (3).
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. Interpretation of notification data should therefore be undertaken with caution.
References
1. UKHSA (2013). ‘Diphtheria: the Green Book, chapter 15’
2. Wagner KS, White JM, Crowcroft NS, De Martin S, Mann G, Efstratiou A. ‘Diphtheria in the United Kingdom, 1986-2008: the increasing role of Corynebacterium ulcerans’. Epidemiology and Infection 2010: volume 138, issue 11, pages 1,519-1,530
3. UKHSA (2023). ‘Public health control and management of diphtheria in England: 2023 guidelines’
4. De Zoysa A, Efstratiou A, Mann G, Harrison TG, Fry NK. ‘Development, validation and implementation of a quadruplex real-time PCR assay for identification of potentially toxigenic corynebacteria’. Journal of Medical Microbiology 2016: volume 65, issue 12, pages 1,521-1,527
5. UKHSA. ‘Diphtheria in England: 2021’. Health Protection Report 2023: volume 16, number 5
6. UKHSA. ‘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 (data to 25 November 2022)’
9. UKHSA (2023). ‘Supplementary guidance for cases and outbreaks in asylum seeker accommodation settings’
10. UKHSA. ‘R3: Vaccine preventable bacteria section request form’