Epidemiological aspects of some equine viral diseases

Abstract


Introduction
The economic value of the horses is highly considerable. So, any infectious threat not only affects the endemic areas but also affects the exportation and importation process (1,2). Viral diseases are colossal threats to the human and animal populations. They have extended their geographic distribution and emerged in new regions of the world (3)(4)(5)(6). Many diseases were underestimated due to using of serological methods as it more available and easier to practice (7)(8)(9). But, in the recent decades, molecular detection and phylogeny become so important in monitoring the spreading (10,11). Morbidity and mortality from these diseases might affect the draft power, thereby, affecting food security and poverty level especially in rural areas (12).
Most equine viral diseases are notifiable ones but the African horse sickness (AHSV), equine influenza virus (EIV), equine viral arteritis (EVA), Equine infectious anaemia virus (EIAV), and equine herpesviruses (EHV) are the most important ones (13). The low economic importance of natural reservoirs (donkeys and mules) adding to its natural resistance to show clear clinical manifestations affects the conducted studies and surveys. Accordingly, they must have the same focus of interest since they are abundant in number and have close contact with horses in several regions (14). The African horse sickness virus (AHSV) is one of the OIE notifiable diseases due to its devastating nature. It is endemic in some South and East countries of Africa adding to Asian South-East countries. The virus's endemicity depends mainly on the presence of the vertebrate reservoir and the lack of safe and effective vaccines for effective control strategies (15).
The EIV is one of the most economically remerging pathogens causing respiratory problems due to its rapid spread and highly contagious nature adding to a wide range of affected hosts (16). The EVA disease has a significant economic impact on the breeding farms due to the occurrence of EVA-associated abortion outbreaks and the virus's ability to create carrier stallions (17). The "swamp fever" is a chronic infectious disease caused by the EIAV of the family Retroviridae. It has a significant economic effect on the equine industry due to its worldwide distribution adding to the obligatory elimination of infected cases (18). The Equine herpes viruses are the most important equine disease not only for their wide spread, but also due to their responsibility for causing different clinical forms adding to developing a latent infection status which prevents complete control of the disease (4,7). Not all available vaccines provide complete protection against abortion or even viremia (19). Egypt is an important centre for raising and marketing the pure breed of Arabian horses. The absence of appropriate monitoring surveys might threaten the horse industry locally and internationally (20). To combat equine diseases, it is imperative to understand their epidemiological situation (21). Accordingly, the presented review aims to outline the epidemiological situation of the most notifiable equine viral diseases, including causative agents, clinical signs, history and incidence, geographical distribution, and prevalence with special concern to the source of infection, and methods of transmission.

Causative agents
The AHSV is a double-stranded RNA virus belonging to the Orbiviruses genus in the family Reoviridae. With a diameter around 80 nm, it has nine antigenically different serotypes. The genome is composed of ten segments. The Orbiviruses are characterised by intragenic recombination occurrence. In AHSV, it was a result of exchanges between live attenuated vaccine viruses and field isolates. This mechanism resulted in increased virulence, expanded host range, increasing viral survival against host defences (22). The EIV type A is classified under the genus Influenza A, family Orthomyxoviridae, it has 8 segments of RNA strands with a negative sense, type D was also found in human and equines. The virus hemagglutinin (HA) and neuraminidase (NA) proteins are the essential surface spikes and antibodies produced against the first one can block virus-cell entrance and antigenic drift at this gene could result in the problem of vaccine failure. While antibodies against NA result in virus aggregation inside the host cell and hinder its release (23). The EVA is an enveloped virus with a 12.7-kb positive-sense, single-stranded, infectious RNA genome. It is classified as the prototype member of the family Arteriviridae, the new genus Equarterivirus. There is only one known serotype. It is highly species specific as it only infects members of the family Equidae (24). The EIAV has a diameter of 115 nm. It contains two copies of single-stranded, positive-sense RNA genome about 8.2 Kbp and is classified under the genus Lentivirus, subfamily of Orthoretrovirinae, and family of Retroviridae. It is related to bovine immunodeficiency virus (BIV) and HIV. As they were derived from a single ancestor. Although viral proteins are immunogenic, but the provoked antibodies do not have the capability of infection elimination (25). Nine herpesviruses have been identified to infect the family Equidae. The EHV1 is classified under genus Varicellovirus, subfamily Alphaherpesvirinae, family Herpesviridae, the virion is 200-250 nm in diameter and has a double stranded DNA of 150 kbp (26). EHV-l and EHV-4 have extensive antigenic cross-reactivity, and both were discriminated as the primary cause of abortion and respiratory signs in different outbreaks (27). (Figure 1).

Clinical signs
Infection of horses with African horse sickness (AHSV) may result in developing one of the 4 clinical forms cardiac, pulmonary, mixed pulmonary and cardiac, adding to the sickness fever form. Mules usually develop pulmonary and mixed forms. Zebras rarely develop serious clinical signs. The mildest form tends to be in resistant species such as donkeys, or horses with partial immunity. This form can also occur in zebras, although mostly are asymptomatic (28) (Figure 2). The equine influenza virus (EIV) infected donkeys could develop more severe clinical respiratory signs compared to other equids due to bacterial broncho-interstitial pneumonia or due to coinfection with pulmonary nematodes. Usually, the infected horses did not develop carriers, and the vaccinated animals may exhibit no clinical signs and may go unnoticed (29). Although the disease is classified as a selflimiting disease and not life-threatening, but the presence of secondary bacterial infection complicates the case (30) (Figure 3). Natural infection with equine viral arteritis (EVA), results in subclinical or mild symptoms, the most significant losses are due to the reproductive form expressed as abortion in 70% of mares. It could occur at any time but mainly after the first third of pregnancy with or without previous signs (24). The infected stallions suffer from deterioration of semen quality, resulting in subfertility status for 2 months (31).
All equines are susceptible for the equine infectious anaemia virus (EIAV), infection. Although any of the disease's signs could appear, the donkeys showed reduced fever and less or no clinical manifestations. The chronic form was developed in horses recovered from the acute infection with moderate to severe haemolytic anaemia, recurrent febrile episode, and weight loss. The resistant animals become inapparent carriers with a reduced intensity of signs within 1-2 years and remain infected for all life span but stress or immunosuppression induce these viremia and reactivation episodes (32).
The equine herpes viruses (EHV) infection usually results in one of respiratory, abortion, neonatal, and equine herpes myeloencephalopathy (EHM) forms. Lesions were more severe in the mare's aborted foetuses in comparison with those from she-donkey. The aborted foetuses showed pulmonary oedema with bronchial secretions, necrotic hepatic areas adding to oedematous and congested placenta (33). The nervous signs are due to ischemic degeneration in the central nervous system. The incubation period for the EHM is challenging to determine because the primary infection could occur a long time before (34).

Prevalence and geographical distribution
Although morbidity and mortality rates due to AHSV are very high, it depends on different factors. The disease is endemic in tropical and subtropical areas of Africa, south of the Sahara, from Senegal in the west to Ethiopia and Somalia in the east and extending as far south as South Africa (35). Most of the serological studies indicated circulating of the disease with a high seroprevalence rate of 75% in the studied donkeys and 63% in horses of Ethiopia and Zimbabwe (36). In Gambia, 96% of the tested horses and donkeys were seropositive for AHS serotype 9 (37). All AHSV serotypes are circulating in Namibia, and Zimbabwe except for AHSV-8 with the AHSV-9 and AHSV-6 were the most prevalent serotypes detected in donkeys (38). A recent outbreak was reported in Thailand with afraid of being a threat to other Asian countries as sometimes the virus jumps out of endemic regions and spread far away as India and Pakistan (39) (Figure 4). The EIV infection is characterised by high morbidity and low mortality rates. In the spring of 2003, the virus was confirmed in a large outbreak in the UK. In 2020 many outbreaks occurred even in the vaccinated animals (40). Since 2007, many South Asian and European countries reported the presence of multiple outbreaks. All of the viruses belong to Florida sub lineage clade 1. Many countries in Africa in 2018 and 2019 reported multiple mortalities in horses and donkeys (35). In Canada, a survey revealed a 56% morbidity rate with the H3N8 was the predominant type. While in a previous study on racing horses the prevalence was 76%.  The EVA has low morbidity and low mortality rates, the worldwide epidemiological studies showed its prevalence across parts in North and South America, Africa, Asia, and Europe. Iceland and Japan are apparently healthy. New Zealand succeeded in the virus's eradication. The seroprevalence of EVA infection varies between and within the same countries (42). In 1998 only 0.6% of the horses showed seropositivity to the EVA in the USA but during 2007, a significant rise was recorded (43). The virus was detected for the first time in Serbia in 2017, with a low rate of 16 % (44). In Poland, the rate raised to be 92% and 71% in tested mares and stallions respectively (45). In the last 20 years, EVA in donkeys was recorded in many countries of Asia, Europe, and America ( Figure 6).
Since the beginning of the 21 th century, multiple outbreaks of EIAV were reported in areas with intensive equine industry. In 2009, a major outbreak was reported in France (46), Germany during 2020 although the country was free since 2017. In Mongolia during 2016, only 1.4% overall seroprevalence rate was recorded, positive samples were relatedness to genotypes from Europe with no relation with those near China and Japan (47). Nearly 3.3% of the examined Brazilian Donkeys sera were found to be positive.
Interestingly, no clinical signs were observed which magnifies their epidemiological role. The disease is highly endemic in South American countries have one of the largest equine populations (48). EIAV tends to reoccur after a long gap of time as in India1999 then 2012 (32). In France during 2000 and 2009 (46). Surveillance of the most important infectious diseases including the EIAV in the UK during 2000 showed an absence of clinical cases (49). Recent surveys in Middle East countries revealed an absence in Israel, Saudi Arabia, and the Gulf area (50) (Figure 7).  The EHV disease is characterised by high morbidity and low mortality rates, however, sometimes deaths could be up to 40%. The disease is endemic worldwide even in countries using the vaccine for control. Outbreaks are notified to the OIE periodically from many countries; France, Great Britain, and Belgium, in the United States, in New Zealand, Australia, Chile, Argentina, Israel, and United Arab Emirates (51) (Figure 8).

Source of infection and methods of transmission
The Culicoide imicola biting midges is the main biological vector for AHSV transmission. Also, Anopheles stephensi and Aedes aegypti were involved in the biological transmission of AHSV. The, but the importance of these types in the epidemiology of the virus remains unclear (52). AHSV was also isolated from the camel tick with transstadial transmission only (53). Furthermore, the brown dog tick was capable of transmission to dogs and horses. An earlier study suggested that Stomoxys calcitrans can mechanically transmit the virus (54). Regarding EIAV, blood from infected cases is the main source of infection. Mechanical transmission usually occurs through horseflies and deerflies of the family Tabanidae. Stable flies (Stomoxys calcitrans), and mosquitoes can transmit the virus but less efficiently. Also, it could be transmitted iatrogenically through transfusion with contaminated blood or its products or bloodcontaminated needles and other veterinary surgical instruments (55). Excretion of virus particles in the different body secretions from sub-clinically infected (partially immunized) or those incubating the disease is the main source of horizontal transmission of many viruses. The EIV is highly contagious and spreads rapidly between susceptible hosts horses as a result of coughing, ocular and nasal discharge. The aerosol can spread effectively through the air up to 1-2 km of distance (56). The same route was cleared in EVA (57), and EHV transmission (58). The aborted tissues and placental fluids contain a high amount of viruses so they are the main source of infection either directly or indirectly through contaminated fomites. Many studies considered latently infected cases are the main source of infection after their reactivation (4).
Venereal virus transmission occurs through natural breeding or artificial insemination with infective semen obtained from acutely infected or carrier stallions (the only reservoir) or even embryo transfer from mares inseminated with infective semen to native recipient ones as in EVA (57. In EIAV possibly could occur if the mare's vagina had lacerations as experimental subcutaneous inoculation of infected semen resulted in disease occurrence (59). Although EHV1 was detected by PCR in the stallion's semen but the risk of transmission by venereal route is unclear (60). Lastly, vertical transmission of EIAV might happen in utero, at parturition, or following the ingestion of infected colostrum or milk. But trans-placental transmission appears to be very rare (25), and sometimes in AHSV (Figure 9).

Conclusion
Equines are of great economic importance in the old and recent history. Most of the equine viral diseases were recorded a long time ago even with different names but with similar clinical signs. Some of these viruses could persist for a long time and form carrier status. Aerosols and body excretions are the main sources of infection with EIV, EVA, and EHV but insect vectors have an important role in the transmission of arboviruses like AHSV and EIAV. Accordingly, adherence to the scientific rules of preventive immunizations and taking all health measures to combat insects, which are the main carriers of some viral diseases that affect horses, are very important ways to reduce horse infection and reduce economic losses.