Equine influenza vaccination in the UK: Current practices may leave horses with suboptimal immunity

Abstract Background Vaccination is integral to preventive healthcare. Despite numerous guidelines on equine vaccination, evidence of current vaccination practices is lacking. Objectives To describe current vaccination practices advised by vets treating horses in the United Kingdom (UK) and compare practices with manufacturer datasheets and current guidelines. Study design Cross‐sectional survey. Methods An online questionnaire was distributed using email addresses acquired through professional registration listings and social media, targeting vets who treat horses in the UK. The questionnaire collected demographic data and information regarding vaccination practices and vaccine hesitancy. Descriptive statistical analysis was performed. Results Questionnaires were completed by 304 UK vets working with horses used for leisure (97.4%, n = 296/304), competition (86.2%, n = 262/304), stud‐work (47.7%, n = 145/304) and racing (40.5%, n = 123/304). Variation was identified in vaccine protocols for competition and noncompetition horses. Fifty‐seven per cent (n = 170/298) of respondents reported variation in advised ‘booster’ frequency; most commonly (n = 118) advising a 6‐monthly vaccination in competition horses and annual vaccination in noncompetition horses. Most common vaccination guidelines volunteered were British Horseracing Authority (68.8%, n = 172/250) and Federation Equestre Internationale (66.4%, n = 166/250). Most vaccination practices were not consistent with datasheet guidance. Only 7.7% (n = 23/300) of respondents complied with datasheet timeframes between the second and third vaccination. Adverse events following vaccination in the previous year were encountered by 66% (n = 199/304) of respondents, representing 2760 adverse events; but only 526 (19.1%) cases were reported to the Veterinary Medicines Directorate. Most common reactions were transient, including stiffness (931), localised swelling (835), lethargy (559) and pyrexia (355). 86.4% respondents reported vaccine hesitancy from horse owners, most commonly due to perception of over‐vaccination, cost and concern regarding adverse events. Main limitations Potential selection, respondent and recall bias. The recent Equine Influenza (EI) and Equine Herpes Virus (EHV) outbreaks in the UK may have altered responses. Conclusions Current equine vaccination practices, although complying with competition rules, are mostly noncompliant with datasheet guidelines, potentially risking suboptimal immunity.


| INTRODUC TI ON
Vaccination is an integral component of preventive medicine in equine practice. Equine vaccination is most commonly performed against equine influenza (EI) and tetanus, with an owner-based survey reporting 71.3% horses were vaccinated for both EI and tetanus in Great Britain 1 with lower vaccination rates in ponies, retired and companion animals. This study, however, is likely to be an overestimation due to respondent bias, and although sufficient data in this area are lacking, crude estimates which take into account vaccine manufacturer sales and the estimated horse population in the United Kingdom (UK) give an approximate figure of only 30% horses that are vaccinated (R. Newton, personal communication, 2020).
There are multiple sources of guidance and regulations on equine vaccination in the UK, particularly for EI; including various competition, riding club and racing rules, [2][3][4] in addition to organisations including the World Health Organisation for Animal Health (OIE). 5 These guidelines often differ from each other and also from the manufacturer's published datasheets, 6 as summarised in Table 1.
With outbreaks of EI, and equine herpes virus (EHV) in the UK in 2019, the effectiveness of vaccination continues to be under close scrutiny. Equiflunet, 7 a free online disease surveillance tool created by the Animal Health Trust, reported 228 laboratory confirmed outbreaks of EI in 2019, most of which affected multiple horses. Of concern were numerous reports of EI in vaccinated animals in the UK and internationally. [8][9][10][11] One factor in vaccination failure is noncompliance with the published vaccination guidelines available at the time which has been demonstrated in cats. 12 However, to date, there has been a lack of data on current equine vaccination practices; whether veterinary advice is consistent with datasheet recommendations and which factors or available guidelines influence vets' decision making.

| MATERIAL S AND ME THODS
An online questionnaire was created using JISC software (JISC Online Surveys © , 2020). The questionnaire was first piloted to 6 veterinary surgeons to assess that the questions were answerable, and the software was effective. No changes were required following the pilot. The questionnaire link was distributed using practice email addresses acquired through the Royal College of Veterinary

TA B L E 1 (Continued)
the number of responses reported for each question varies and is stated throughout.

| Respondents
The survey resulted in 304 valid responses from veterinary surgeons treating horses. Seventy-four per cent respondents worked only with horses; others were mixed practitioners. 55.2% were less than or equal to 10 years graduated. The respondents' workload consisted of a combination of leisure horses (97.4%), competition horses (86.2%), stud (47.7%) and racing (40.5%). Respondents were asked to indicate the interval that they advise following the primary course of vaccinations and prior to attending an event. Only 10.2% (n = 26/254; 95% CI 7.1%-14.6%) of respondents complied with the datasheet recommendation of a minimum of 14 days prior to attendance, all other respondents advised return to competition prior to this ( Figure 5).

| Adverse drug reactions following vaccination
Over half of respondents (65.5%, n = 199/304) encountered at least one adverse drug reaction (ADR) following vaccination in the

| Vaccine hesitancy
The and 11.1% (n = 29/298; 95% CI 6.9%-13.6%) encountered it often (more than monthly). The most common reasons for vaccine hesitancy in horse owners encountered by respondents were as follows unnecessary need of vaccination, previous or anticipated ADR, side effects and lack of effectiveness (Table 3). antigens; most commonly by incorporating EI vaccination into protocols for geriatric/unridden animals (as opposed to tetanus alone previously).

| D ISCUSS I ON
This study provides insights into equine vaccination practices performed by vets in the UK. As expected, 14  This study demonstrated that 29.6% of respondents may perform first vaccination (V1) before 6 months of age, although age of first vaccination has been correlated with the presence of maternally derived antibodies and both of these factors may impair the establishment of an effective humoral response. 15 Foals receiving V1 at 6 months of age had significantly higher antibody levels (optimal immunity) 1 month after V3 than foals receiving V1 at 4 months (suboptimal immunity). Differing levels of immunity can result in alteration in viral shedding and clinical signs. The single radial haemolysis (SRH) assay of antibodies is predictive for disease severity. SRH antibody levels greater than 85 mm 2 are associated with reduced clinical signs and levels between 120 and 154 mm 2 are associated with resistance to clinical disease. 16 All manufacturers of authorised EI products within the UK advise a 3rd vaccination (V3) 5 months following the 2nd vaccination (V2) due to the duration of immunity (5 months) following V2. 6  Another concern highlighted by this study is the low level of ADR reported despite frequent encounters of adverse events.
Participants reported encountering 2760 adverse events in the last 12 months, of those events only 19.1% were formally reported. This is an area which requires improvement as a profession in order to provide necessary feedback to pharmaceutical companies and the veterinary medicines directorate (VMD) for drug safety. The concern about the risk of ADR appears to be a significant contributing factor when encountering vaccine hesitancy in horse owners. The risk of ADR was the most common reason given for refusal of Hendra vaccination by Australian horse owners. 25 Vaccine hesitancy (VH) has been defined by the WHO as "delay in acceptance or refusal of vaccines despite availability of vaccination services" and was categorised as one of the top 10 threats to global health in 2019. 13 This study identified vaccine hesitancy or reluctance occurring in owners in the equine sector, with 11.1% practitioners encountering VH frequently. A recent meta-synthesis study of childhood VH 26 outlines similar themes of causation of VH to our equine study such as concern regarding side effects, and mistrust of health professionals, pharmaceutical companies and the information which they deliver. With regard to childhood vaccination, the doctor's advice has been shown to be the most important predictor of vaccine acceptance. 27,28 Awareness of this growing problem is, therefore, vital in the veterinary field, in order to address the underlying issue, as reduced uptake of vaccination will in turn affect our ability to promote herd immunity. Further research exploring horse owners' perception of vaccination is required.
As this study was a cross-sectional questionnaire requiring voluntary uptake, there was the potential for selection bias of the respondents. The ADR section and vaccine hesitancy section of the survey required respondents to estimate the frequency of hesitancy and adverse events encountered, therefore, may not be entirely accurate due to recall bias. A prospective study based on vaccination protocols would be welcome. It is possible that the recent EI and EHV1,4 outbreaks in the UK just prior to this survey could have affected the responses given. In an attempt to manage the effect of the recent EI outbreak on vaccination protocols, respondents were asked to report any changes in their practice in the last 12 months. In light of the EI outbreak, many competition guidelines altered their ruling to reduce the duration between booster vaccinations due to evidence of waning immunity over time since last vaccination. 8,10,18,29 These changes were supported by the change in practice of vets in this study, with 97.2% of respondents increasing the frequency of vaccination, most commonly (57.4%) to 6 monthly.
In addition to this, there was a human health pandemic (COVID19) at time of authorship, though following closure of the survey, which also has implications for equine vaccination. The RCVS and British Equine Veterinary Association (BEVA) advised against routine vaccination during the period of lockdown, and as a consequence many competition guidelines were relaxed to allow annual vaccination. This added a further level of complexity for practitioner's decision-making regarding vaccination, and vets need to be aware of the duration of immunity stated by the manufacturers' datasheet as horses vaccinated outside this schedule may not be fully protected.
In conclusion, this study has identified a lack of compliance with manufacturers' datasheets that may promote immunity gaps leading to a reduction in the effectiveness of vaccination programs within the UK equine population. Such gaps may increase the risk of EI outbreaks, even among competition animals complying with the competition's ruling. Updating competition requirements to one strategy across all equestrian disciplines could reduce the number of differing guidelines and, in turn, improve equine welfare.

CO N FLI C T O F I NTE R E S T S
MSD (source of funding) produce a range of equine vaccinations; however, they were not involved in the development of the survey, and they did not have access to the results.

AUTH O R CO NTR I B UTI O N S
A. Wilson contributed to study execution, data analysis and interpreta-

E TH I C A L A N I M A L R E S E A RCH
Ethics approval was obtained through the University of Liverpool Veterinary Ethics Committee (VREC838).

OWN ER I N FO R M ED CO N S ENT
Completion of the questionnaire was taken as participant consent.

DATA ACC E S S I B I L I T Y S TAT E M E N T
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

PE E R R E V I E W
The peer review history for this article is available at https://publo ns.com/publo n/10.1111/evj.13377.