Mandatory reporting urged after diphtheria-like infection found in horse in Britain

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The characteristic pseudomembrane is classically seen in diphtheria. The horse in the case study had a similar lesion. Photo: User: Dileepunnikri, CC BY-SA 3.0 via Wikimedia Commons

The case of a diphtheria-like infection confirmed in a gelding in Britain indicates a role for horses as reservoirs for the bacterium Corynebacterium ulcerans, which can infect a range of species.

Diphtheria and diphtheria-like infections are caused by three Corynebacterium species, Corynebacterium diphtheriae, Corynebacterium ulcerans, and Corynebacterium pseudotuberculosis.

All can harbor the gene responsible for the production of diphtheria toxin, a potentially lethal exotoxin.

While C. diphtheriae causes classic human diphtheria and is carried almost exclusively by people, C. ulcerans and C. pseudotuberculosis are mainly veterinary organisms.

Nevertheless, both have infected people, with clinical signs indistinguishable from those caused by C. diphtheriae being increasingly reported.

Flavia Zendri and her fellow researchers, in a case report published in the journal Frontiers in Veterinary Science, noted that while the incidence of classic human diphtheria has declined globally as a result of extensive vaccination programs, C. ulcerans has been established as an emergent pathogen in several countries, including France, Britain, Germany, and the United States.

Consequently, human infections associated with toxin-producing C. ulcerans have exceeded those caused by toxigenic C. diphtheriae in many industrialized countries, including Britain.

C. ulcerans infections in people were originally described following livestock exposure and consumption of unpasteurized milk, but more recently domestic pets have been progressively implicated in cross-species transmission.

Occasionally, they said, a link between the toxin-producing C. ulcerans strains isolated from pets and their respective owners has been established.

Companion animals carrying C. ulcerans, particularly cats, are often free of symptoms but may present with a clinical infection involving upper respiratory disease.

In their study, the researchers described the admission of a six-year-old bay warmblood-cross gelding to a British university veterinary hospital late in 2019. The horse had been affected by a nasal discharge, comprising pus and mucus, from his right nostril for 10 days. Imaging showed no sinus or dental involvement.

An endoscopic examination revealed a large membrane similar to those seen in cases of diphtheria. Swabs were taken for analysis.

Investigation revealed the presence of C. ulcerans and Streptococcus equi subsp. zooepidemicus.

Given the risk of spreading the infection, the horse was moved to an isolation unit and infection control measures implemented.

Molecular-based testing confirmed the presence of the toxin-producing form.

The horse was treated with antibiotics and showed progressive clinical improvement until the nasal and pharyngeal lesions healed three weeks after admission. No C. ulcerans was isolated from follow-up nasal specimens obtained four weeks after hospital admission. At this point, all antimicrobial treatment ended and the horse was discharged upon full clinical recovery a week later.

Discussing their findings, the researchers said: “To the best of our knowledge, horses represent an as yet undescribed companion animal species able to carry and develop C. ulcerans-associated infection resembling human respiratory diphtheria.

“Hence, horses may be a reservoir of this zoonotic pathogen, and a differential diagnosis of respiratory diphtheria-like illness should be considered in this species based on clinical findings.”

Diphtheria, they noted, is a statutory notifiable disease in people in Britain, but animal-associated toxigenic C. ulcerans is not reportable in England.

However, their preliminary microbiological findings were communicated to the national public health and veterinary authorities because of the concern over possible zoonotic implications — that is, the potential for it to jump to humans.

The equine strain was referred to Public Health England for further diagnostics, and authorities initiated an outbreak investigation, with comprehensive contact tracing carried out for 49 people who had been exposed to the ill horse.

Diphtheria-containing booster vaccinations were given, and swabs were taken from 46 people, including the horse owner, two family members, and 43 equine surgeons/veterinary students.

None was positive for C. ulcerans, and the public health investigation was closed.

Timely communication between the laboratory and the equine clinicians, and their collaboration with the medical, veterinary, and public health authorities, enabled prompt confinement of the infection, the researchers said.

Given the prior detection of the bacterium in sick humans in Britain, further studies are warranted to explore the epidemiology and possible relationship between equine and human C. ulcerans infections, the study team said.

“This study suggests that toxigenic C. ulcerans isolation and associated animal infections should be included on the list of reportable zoonotic organisms, to protect public health.

“This report warrants future studies on the carriage and infection of equids with C. ulcerans to further understand the role that infected or colonized horses may play in the epidemiology of human diphtheria-like zoonotic infections.”

The study team comprised Flavia Zendri, Cajsa Marie Isgren, Matthew Sinovich, Peter Richards-Rios, Katie Hopkins, Katherine Russell, Natalie Groves, David Litt, Norman Fry, and Dorina Timofte, variously affiliated with the University of Liverpool and the National Infection Service.

Zendri F, Isgren CM, Sinovich M, Richards-Rios P, Hopkins KL, Russell K, Groves N, Litt D, Fry NK and Timofte D (2021) Case Report: Toxigenic Corynebacterium ulcerans Diphtheria-Like Infection in a Horse in the United Kingdom. Front. Vet. Sci. 8:650238. doi: 10.3389/fvets.2021.650238

The case report, published under a Creative Commons License, can be read here.

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