A risk assessment of equine piroplasmosis entry, exposure and consequences in the UK

Abstract Background Equine piroplasmosis (EP) is currently not endemic in the UK, despite a lack of formal surveillance and the presence of carrier horses in the equine population. Pathogen establishment would have significant welfare and economic impacts on the national equine industry, but the disease is often overlooked by UK practitioners. Objectives To assess the risk of disease entry, exposure and consequences to the UK equine population. Study design Qualitative risk assessment. Methods A qualitative risk assessment was constructed utilising the current World Organisation for Animal Health (OIE) published framework for importation risk assessment, assessing the key areas of disease entry, exposure and consequences to the UK equine population. Results The overall risk of EP entry to the UK via importation of infected equidae with acute disease is very low but considered medium with subclinical carrier animals. Entry via importation of ticks or the importation of blood is considered very low. The risk of EP exposure to susceptible equidae in the UK is considered low by the infection routes of tick‐bites, contaminated needles and contaminated blood, but very high via transplacental transfer. However, the consequences of EP endemic establishment are considered of high significance to the UK equine industry. Main limitations A lack of available numerical data for events and variables in disease import risk meant a qualitative assessment was the most practical method for this scenario. Conclusions This risk assessment highlights that EP positive animals are able to enter and are currently present in the UK, and that conditions do exist that could allow forward transmission of the disease. It has highlighted a gap in existing policy where the UK falls behind OIE guidelines and has suggested steps to correct this discrepancy and improve national biosecurity.


| INTRODUCTION
Equine piroplasmosis (EP) results from single or co-infection with the intracellular blood apicomplexan parasites Theileria equi and Babesia caballi and is a disease of global welfare and economic significance. 1 Only a tenth of the global equine population is estimated to live in areas free of endemic disease, 2 including the UK, Ireland, USA, Australia and Japan.
EP is transmitted through the bite of infected tick vectors, however artificial transmission through iatrogenic blood-to-blood contact is possible. Clinical disease is similar regardless of the infecting parasite species and presents in both acute and chronic forms. Acute cases typically present with pyrexia, lethargy, dehydration, anorexia and anaemia, with death occurring in severe or neglected cases. 3 In the chronic form, clinical signs are milder with animals displaying fluctuating malaise, anorexia, weight loss or reduced performance. 2,4 Infected animals become carriers, acting as reservoirs for further infection. This carrier status can persist for years 5 or life, 6 even continuing despite medical treatment, 7 with potential for acute recrudescence in times of co-infection or stress.
Equine piroplasmosis has serious effects on the reproductive capacity of an equine population. Transplacental transmission of T. equi in infected mares can result in abortion, fatal neonatal piroplasmosis at birth or the offspring being born a sub-clinical carrier of disease. [8][9][10] Ultimately the disease has significant implications for animal welfare and fertility as well as local and global equine industry and trade.
Historically, EP has not established in the UK due to a lack of competent tick vector species. 11 However, Dermacentor reticulatus, a major EP vector species, is increasingly being identified as endemic in some areas of the British Isles. 12 The UK does see positive cases associated with imported animals, 9,13 but tick-borne transmission within the British Isles has yet to be recorded despite the presence of EP positive animals.
Unlike other EP-free countries, there is no official obligation to report the disease in the UK, and UK cases are only monitored indirectly via EP diagnostic submissions to laboratories contributing to the Equine Quarterly Disease Surveillance Report. 14 An import risk analysis encompasses the steps of hazard identification (the pathogen or risk to be considered), risk assessment (entry, exposure and consequence assessment and risk estimation associated with the hazard), risk management (options available to manage the hazard) and risk communication (information exchange with affected parties and stakeholders). 15 Here the authors focus primarily on the risk assessment component of the analysis, with the purpose of highlighting the most important risks and consequences to be considered by veterinarians and individuals involved in equine importation to the UK. Consequently, the goals of this qualitative risk assessment (QRA) are to estimate the likelihood and consequences of introduction and onward spread of EP into the UK and discuss recommendations to mitigate the threat.

| MATERIALS AND METHODS
This QRA addressed the specific risk question 'What is the current risk of EP being introduced to the UK and disease becoming endemic in UK resident equines?' providing a detailed account of entry and exposure pathways, and an assessment of consequences from EP introduction.
Qualitative risk assessments express the likelihood of a risk using words (e.g. negligible to high risk), in contrast to quantitative risk assessments which uses numerical measures, such as the number and frequency of events, to numerically express the probability of a risk and the magnitude of its effect.
At present, there is lack of either available, comprehensive or up-to-date numerical data for UK equine and tick population size and distribution, the current prevalence of EP in UK resident equines, the efficacy of EP transmission by indigenous UK tick species, and many other important variables surrounding UK EP entry and transmission. Consequently, this disease import risk assessment necessitated a qualitative rather than quantitative risk assessment approach for the UK situation. 16 This QRA was constructed utilising the comprehensive World Organisation for Animal Health (OIE) published framework and guidance for importation risk assessment 15 which is adopted by the UK Department of Environment, Food and Rural Affairs (DEFRA). 17 This QRA follows three key areas of the OIE framework: i. Entry assessment -What is the probability of EP entering the UK from EP disease endemic countries?
T A B L E 1 Terminology for assessed level of risk and uncertainty level 16,18 Risk term Definition  (Table 1). Where applicable, overall risk estimates probabilities were combined using a previously described matrix 16 (Figure 1).

| Entry assessment
Three likely risk pathways for EP entry into the UK have been identified ( Figure 2). A summary of entry pathway risks, described in detail below, is presented in Table 2.

| Importation of EP infected carrier equidae
What is the likelihood of an EP infected animal being able to enter the UK?
There are currently no formal requirements to screen equidae for EP prior to or at importation. However, animals are required to be certified free of clinical disease following clinical examination at a pre-export inspection by an official veterinarian of the exporting country on the day of loading for export 19 and declared by the owner or breeder to have been free from contact with equidae suffering from contagious or infectious disease in the 15 days prior to examination. 20 Additionally, animals may be subject to post-import inspection at UK Border Control Posts. 19  What is the likelihood of an animal imported to the UK from an endemic area being EP positive?
The likelihood of an imported individual being EP positive will vary with the country of origin and previous travel history, in Europe alone overall seroprevalence of T. equi and B. caballi in endemic countries is 30% and 8% respectively, and PCR prevalence is 25% and 2% respectively. 24 Due to the high financial costs involved in international equine transport, it is assumed that frequently travelled performance animals and high value animals represent the greatest proportion of imported equines, and these animals are often subject to more stringent biosecurity controls, such as the HHP scheme, 23 to reduce the risk of disease dissemination. However, a lack of published data gives this assumption a high uncertainty level.
It is concluded that the risk of an imported equid being EP positive is medium, although may vary from low to high depending on the animal's travel history. The overall risk estimate of EP into the UK is considered very low in case of animals with acute disease, but medium through the introduction of animals with subclinical disease.

| Importation of EP infected ticks
What is the likelihood of an EP infected tick being able to enter the UK?
There are five known genera of ticks that can act as EP vectors; Amblyomma spp., Dermacentor spp., Haemaphysalis spp., Hyalomma spp. and Rhipicephalus spp. 25 All are multi-host ticks and in EP endemic areas feed on cohabiting non-equine animals, and these animals may also act as a vehicle to transport an EP positive tick into the UK. 26,27 Ectoparasiticide treatment of equidae is not required before UK importation. 19 The probability of detecting ticks on an EP carrier animal during the pre-export inspection would depend on the anatomical location, number and age of the ticks present. Instances have been documented of adult ticks from EP competent species being detected on horses after UK importation. 28 Therefore, there is a low risk of an EP infected tick entering the UK on imported equidae.
All bovine animals imported to the UK are also subjected to a compulsory pre-export veterinary examination, with additional compulsory ivermectin treatment for the prevention of warble fly immediately post-import. 29 Although ivermectin is not directly licensed for use against ticks, there is evidence of activity against a range of tick species. 30 Consequently, the risk of these species transporting an EP infected tick into the UK would be very low.
Ovine, caprine and other ungulate imports are also subject to the same pre-export inspection, but not compulsory warble fly treatment. 31,32 There is therefore a low risk of an EP infected tick being imported with these animals.
Pet canines and felines require a pet passport or animal health certificate prior to UK entry 33

| Importation of EP infected equine blood
Transfusion with EP infected equine blood is a viable method of transmission. 7,38 The importation to the UK of whole equine blood is tightly regulated due to concerns over African Horse Sickness and other pathogens. Importation of equine blood products for purposes other than research require specific authorisation from the Animal and Plant Health Agency (APHA) Import of products, animals, food and feed system (IPAFFS). 39 General licences for research purposes are available for importation of heat treated blood, 40 but certain samples may require specific APHA authorisation. 41 The stringent controls on importation of blood from equidae mean the risk of importing EP via infected blood is very low. However illegal importation of blood poses an ever present disease risk, as demonstrated with the 2006 EIA outbreak in Ireland resulting from the illegal importation of equine serum from Italy. 42 The risk of illegally imported blood being EP infected is considered medium.
The overall risk of EP entry via infected blood should be considered very low.  Table 3.

| Vector-borne transmission
What is the likelihood of UK ticks acquiring EP infection from an imported carrier animal?
Dermacentor reticulatus is the only indigenous UK tick species known to be capable of EP transmission and has a limited distribution. 12 An imported carrier animal would have to become resident in an area with an active population of ticks to increase the risk beyond a negligible level.
Transmission of EP from a carrier animal to D. reticulatus through tick feeding has not been directly studied, but studies of other tick species have shown efficiencies of between 7%-50%. 43  Wales, Devon and Essex, 12 with the latter linked to an outbreak of canine piroplasmosis. 44 The UK currently operates the Public Health England's Tick Surveillance Scheme (TSS). 45 This passive scheme relies on voluntary submissions from members of the public, veterinarians, health and wildlife workers. 46  Exmoor, although this is widely accepted to be a substantial underestimate due to the problem of horse abandonment on the moor, 47 and an estimated 1500 animals on Dartmoor. 48 With no formal surveillance of either population numbers or EP disease within these animals, they form an area of potential EP exposure and disease reservoir.
The life cycle of D. reticulatus also has an influence on exposure risk.
The tick is extremely hardy, able to live up to 4 years without a blood meal, remaining active during the winter and able to survive prolonged periods below À0 C. 37 Consequently, EP positive ticks could provide an environmental threat to grazing animals for a number of years.
There are no specific data regarding D. reticulatus, but other Dermacentor species can transfer B. caballi from one generation of tick to the next via transovarian transmission, 49  The susceptibility of naïve equidae to tick-borne EP is well documented 38 and a 2009 outbreak in Texas, USA, saw the efficacy of tick driven EP spread result in 81.1% EP seropositivity within exposed horses over a period of months. 54 In that locality a novel vector Amblyomma cajennense was identified as the primary tick vector, highlighting that endemic tick populations may assume increased importance after arrival of the pathogen in a new locality.
Given the limited existence of UK equid populations in areas of vector tick populations, 12 the risk of a susceptible animal being exposed to an EP infected tick should be considered low.
However, the risk of EP infection by an infected tick feeding on a susceptible equid should be considered medium.

| Mechanical transmission
What is the likelihood of hypodermic needles and equipment becoming contaminated by an EP carrier animal?
Legitimate routine procedures such as diagnostic sampling, treatment and vaccination, along with other illicit practices, 55  Therefore, the general risk of hypodermic needles and equipment being exposed to EP infected blood should be considered medium, and the risk of contamination following use on known EP carrier animals should be considered high.
What is the likelihood of EP contaminated needles or equipment transferring infection to a susceptible equid?
Disposable syringes and hypodermic needles are both inexpensive and readily available in the UK, as are pathways for their safe disposal.
It is assumed there is widespread good practice among veterinary professionals regarding needle hygiene and disposal.
However, episodes of poor practice do occur; a Newmarket equine fertility unit during the 1990s saw EP transmission to 61 of 66 animals due to syringe sharing, 13 and the sharing of needles between horses has been implicated in disease spread in Australia 58 and the USA. 55,59 There have been no recorded instances of disease transmission via equipment other than needles and syringes.
The risk of susceptible equidae being exposed to contaminated needles and equipment is considered low. Given previous reports, the risk of infecting a susceptible animal with a contaminated needle or syringe should be considered high. The risk of EP infection via other blood-contaminated equipment should be considered very low.

| Haematological transmission
What is the likelihood of a susceptible equid being infected through transfusion of EP infected blood?
The intravenous transfusion of naïve animals with infected blood is highly efficient and the preferred method of inoculation for experimental infection studies. 7 The illicit nature of this practice makes quantifying the significance of this risk difficult, although it is assumed that such practices are not widespread in the UK.
There has been no study of the capability of EP to survive storage in blood bags, but another piroplasm, Babesia microti, can remain infective in blood stored at 4 C for up to 21 days. 62 It is assumed that this may apply to T. equi and B. caballi, but the uncertainty of this statement is high.
Consequently, the risk of susceptible equines being exposed to EP infected blood should be considered low, however the risk of susceptible equidae becoming infected from the transfusion of EP infected blood should be considered very high.

| Transplacental transmission
What is the likelihood of an unborn foal being born infected from an EP carrier dam?
Theileria equi can be transmitted transplacentally to foals from as early as month four of gestation 10  mares in one study. 10 Carrier mares can continue to birth EP positive foals for several years. 9 All foals born to an EP infected dam are exposed, so exposure risk should be considered very high. Given an apparently high rate of infection, the risk of neonate infection from an infected dam is high.

| Consequence assessment
An outbreak via the described exposure pathways carries direct and indirect consequences (Figure 4).

| Direct consequences
Outcome of exposure in animals The risk of an animal being infected in the UK is low.
However, the severity of the consequences will vary between individuals.
Considering acute disease cases, outbreaks in Florida 2008 55  Consequences at index premises, regional and national level Consequences at index premises, regional and national level Consequences at index premises and regional level disease are likely to be severe, with mortality rates as high as 69% observed in untreated naïve animals. 63 Mortality within those animals developing chronic disease or carrier status is likely to be very low, only occurring in the event of acute disease recrudescence. However

Production and performance losses
Despite low mortality in chronic cases, productivity losses can be significant. In South Africa, EP is a common cause of abortion 2 with up to 11% of abortions in Thoroughbred mares attributed to There is also concern regarding reduced athletic performance in carrier animals, 10,56 with South African reports suggesting around 2% of young stock are lost from the industry before their first race due to EP related poor performance or disease, 65 although the effect of EP status on performance has recently been debated. 66 Given the potential for a high rate of morbidity before disease is detected, chronic EP infection poses the most likely threat of high direct consequences on both productivity and performance.

Effects on domestic equine industry and trade
The UK has a significant equine industry 67  Thus, the economic consequences of endemic EP to the UK equine industry would be high.

Effects on international equine trade
A UK EP outbreak may lead to countries banning equine imports, such as seen with a 5-month Japanese ban of French imports in February 2016 following the identification of EP-seropositive foals in a French shipment. 68 Establishment of EP within the UK equine population, and subsequent change in national disease status, would not only restrict the number of animals available for export to certain countries, but potentially threaten existing movement policies.
The consequences to international trade following an EP outbreak should be considered high to very high depending on the extent of the incident.

Disease control and eradication costs
Florida provides a pertinent example of tick-born EP eradication difficulties and expense. Following EP introduction with imported Cuban horses, an intense state eradication programme was initiated in 1962, with eradication only declared 26 years later at a total cost of over $12 million to the state. 69 Rapid containment and eradication of EP incursion has only ever been achieved when spread has occurred via mechanical methods, such as the later 2008 Florida outbreak. 55 Consequently, attempts to control and eradicate an incursion of EP into the UK would have high financial and resource costs.

Surveillance of imported equidae
There is currently no EP screening required for entry of equidae into the UK, unlike other EP-free countries. The USA has particularly stringent entry requirements that includes pre-import inspection for ectoparasites and a quarantine period. 70