Overview on infectious diseases

Having agreed to write this article, I was unsure how to proceed, as the title is vast and I could probably fill an entire issue.

Therefore, I have decided to focus on a few key developments for infectious disease control and new incursions of disease.

Notifiable disease update

Last summer, I wrote an article for Vet Times about exotic diseases in cattle, sheep and pigs, highlighting what vets and their farmers needed to worry about (VT53.37). The APHA updated its contingency plan (17 July 2023) for exotic notifiable diseases of animals in England. In this plan, the following were highlighted as being of most concern: avian flu and Newcastle disease, foot-and-mouth disease, rabies, bluetongue (BT), African swine fever and classical swine fever, African horse sickness and lumpy skin disease. When I wrote about bluetongue virus (BTV), I did not anticipate then that we would have another outbreak quite so soon (we had been BTV free since 2010). BTV infects all species of ruminant, with severe disease usually in certain breeds of sheep and deer, cattle usually acting as reservoirs of infection, and is transmitted by biting midges.

Typical clinical signs include pyrexia, excessive salivation, depression, respiratory signs (dyspnoea, panting, nasal discharge), hyperaemia of the muzzle, lips, face, eyelids and ears, leading to oedema. The tongue can become hyperaemic and oedematous, leading to a “blue tongue”. The hyperaemia can spread to the coronary band of the hoof, causing coronitis and lameness. You may also see ulceration of the oral mucosa.

The outbreak certainly was not the serotype we were expecting, with BTV-1, BTV-4 and BTV-8 already present on the continent. BTV-8 has been endemic in France since 2015, with a new strain identified in August 2023 that causes uncharacteristic clinical signs of BT with pyrexia, mouth ulcers and coughing.

Current BTV-8 vaccines do appear to be effective, although it has spread to neighbouring countries.

In September 2023, BTV-3 was identified in the Netherlands and, subsequently, found in the UK in December 2023. No commercially available vaccine exists in the EU at the time of writing, and the existing vaccine serotypes do not provide cross-protection.

The route of BTV-3 incursion into the Netherlands is unknown, but the initial infection sites were approximately 20km from Schiphol Airport and may have arisen due to infected midges catching a lift and arriving by plane. BTV does not pose a threat to human health, but is notifiable in the UK, meaning any suspicion of disease must be reported immediately.

Lower winter temperatures decrease midge activity and BTV transmission; however, on 19 April the Government issued a warning, as we are now out of the seasonal low vector period, with biting midge activity increasing with the warmer spring weather, so we need to be vigilant.

BTV has continued to circulate on the continent, increasing the risk of windborne incursion.

Farms close to the east coast (Norfolk to Kent) and south coast (Kent to Devon) are considered at highest risk of incursion, and vets should advise their clients to monitor for clinical signs of BT.

We also need to ensure clients exhibit caution when purchasing and moving animals from abroad to avoid buying in new strains which are circulating elsewhere; within the UK, we also need to ensure infected animals are not moved to uninfected areas.

“The Oxford Covid-19 vaccine, which was important in halting the recent pandemic, highlighted what can be achieved with a viral vector vaccine.”

 

While writing this article, we had another notifiable disease occur with a single classical bovine spongiform encephalopathy (BSE) case confirmed on a farm in Ayrshire. The animal died on farm following clinical signs consistent with BSE.

Affected cattle do not usually show signs of BSE until they are at least four or five years old, with clinical signs developing over a period of weeks or months. Signs include behavioural changes, with animals appearing apprehensive or nervous with repeated, exaggerated reactions to touch or sound, and can show aggression towards humans and other cows. A high-stepping gait – particularly the hindlegs – may be observed and affected animals are often reluctant to cross concrete or drains, turn corners, enter yards or go through doorways. The first sign often reported by dairy farmers is manic kicking during milking or reluctance to allow milking.

Including this case, only five cases of classical BSE have confirmed in the UK since 2014. These cases are expected and in line with projections for the tail end of the 1992 epidemic. The Government highlights that no risk exists to human health or food safety, as the animal was a breeding animal not intended to enter the food chain.

Emerging infectious diseases

Earlier this year, vets were alerted to a syndrome occurring in lactating dairy cattle in northern Texas. The cattle presented with reduced feed intake and rumination, and an abrupt drop in milk production. The milk had an appearance like colostrum; thickened and a creamy yellow.

On affected farms, incidence peaked four to six days after the first animals were affected and then tapered off after 10-14 days, with most animals slowly returning to regular milking. Clinical signs were commonly reported in multiparous cows during mid to late lactation, with 10 per cent to 15 per cent morbidity and low mortality.

Initial testing failed to reach a diagnosis. Then, in early March 2024, similar clinical cases were reported in dairy cattle in other south-western states. Deaths of wild birds and domestic cats were also observed within affected farms in the Texas outbreaks. The domestic cats were fed raw colostrum and milk from sick cows. Clinically affected cats were depressed, had stiff body movements, ataxia, blindness, circling, copious ocular nasal discharge, an absence of menace reflexes and pupillary light responses, and a weak blink response. In these cats, a 50 per cent mortality rate was reported.

On 21 March, milk and tissue samples from cattle and tissue samples from the deceased cats tested positive for influenza A virus (IAV), with high levels of viral nucleic acid found in milk. Subsequently, the virus was confirmed and characterised as highly pathogenic avian influenza (HPAI) H5N1 virus by the US Department of Agriculture’s National Veterinary Services Laboratory (25 March 2024; Burrough et al, 2024).

The H5N1 strain has been circulating since it was first detected in China in 1996. Since 2021, it has been spreading ferociously in birds globally, killing hundreds of millions of domestic and wild birds and occasionally infecting mammals (Kozlov and Mallapaty, 2024). Previous reports exist of IAV infection in cattle in Japan in 1949 and Europe in 1997-98 and 2005-06, with clinical signs including milk drop; however, this is the first widespread outbreak to be reported in cattle caused by H5N1.

In this outbreak, cattle are thought to have been initially infected by ingesting feed or water contaminated with faeces from infected wild birds; however, it seems likely cow-to-cow spread has occurred as disease developed in resident cattle herds in other states that received infected cattle, and scientists are trying to work out if this has occurred and how. Only dairy cattle have been affected so far.

The high levels of virus found in milk could suggest that cows are being infected through contaminated surfaces at milking. Pasteurisation of commercial milk mitigates risks for transmission to humans, but consuming raw milk could pose a risk to human health (Burrough et al, 2024; Kozlov and Mallapaty, 2024).

At the time of writing, one dairy worker in Texas has been infected, and the virus has been confirmed to be closely related to the strains found in the dairy cattle. This worker is recovering, with the only clinical sign being conjunctivitis (Looi, 2024).

Infectious disease control developments

At the end of 2023, a new cattle vaccine became available in the UK against bovine coronavirus (BCoV). The vaccine Nasalgen-C is produced by MSD Animal Health and is for bovine respiratory disease (BRD). BCoV is known to cause enteric disease with enterocolitis in calves and winter dysentery in adult cows, but the role of the virus in BRD has been poorly understood. The first report implicating BCoV as a respiratory pathogen was in the 1980s, and the virus has been identified in nasal secretions and other respiratory samples (Ellis, 2019; Rahe et al, 2022).

Several studies have reported that BCoV is among the most frequently detected viruses in BRD in calves. Infection of just BCoV is thought to cause only mild or moderate clinical signs, perhaps explaining some of the difficulty in earlier work; however, latest work has demonstrated that BCoV infection increased Pasteurella multocida adherence, highlighting the role BCoV plays in mixed infections (Fahkrajang et al, 2021).

This vaccine can be given from the day of birth onwards. As it is an intranasal vaccine, calves are protected from around five days after vaccination, and with growing concerns over antimicrobial use and the cost of BRD, this provides us with another tool to help control and reduce BRD on farm. 

With growing concerns about antimicrobial and anthelmintic resistance and emerging diseases, vaccines probably do represent the single most cost-efficient and reasonable way to combat and eradicate infectious diseases.

Traditionally, vaccines consist of either inactivated/attenuated versions of the entire pathogen or subunits of it. This is in comparison to novel experimental vaccines that employ nucleic acids to produce the antigen of interest directly in vivo and include DNA plasmid vaccines, messenger RNA (mRNA) vaccines and recombinant viral vectors. Vaccines produced using nucleic acid have several advantages, including their ability to induce durable immune responses, high vaccine stability and ease of large-scale manufacturing.

Viral vectors have been used to deliver antigens for more than 40 years. The Oxford COVID-19 vaccine, which was important in halting the pandemic, highlighted what can be achieved with a viral vector vaccine and has pushed forward the development of viral vector vaccines. It was also discovered during the pandemic that heterologous vaccination strategies using vector/mRNA vaccines could improve immunity (Travieso et al, 2022).

In 2023, the Nobel prize for physiology or medicine was awarded to Katalin Karikó and Drew Weissman for their groundbreaking, decades-long work on mRNA that enabled the unprecedented rapid development of the mRNA vaccines that helped to stem the COVID-19 pandemic.

This work has provided us with the possibility of producing novel vaccines against infectious diseases where traditional vaccine development has been unsuccessful.

I often say to our veterinary undergraduates that I believe vaccine developments from the work on Covid-19 ones will play a massive role in veterinary and human medicine over their lifetime as veterinary surgeons.