Keywords

4.1 Prologue

All known porcine coronaviruses (CoVs) belong to the genera Alphacoronavirus, Betacoronavirus and Deltacoronavirus of the subfamily Coronavirinae, in the family Coronaviridae, of the order Nidovirales (de Groot et al. 2008) [https://data.ictvonline.org/taxonomy-search.asp?msl_id=30 (Fig. 4.1)]. Affections of gastrointestinal, respiratory, peripheral and central nervous systems are usually visualised. Five swine CoVs are recognised: (1) the transmissible gastroenteritis virus (TGEV), first defined in 1946; (2) the porcine respiratory coronavirus (PRCV), a mutant of TGEV, isolated in 1984; (3) the porcine epidemic diarrhoea virus (PEDV), isolated in 1977; (4) the PHEV (porcine haemagglutinating encephalomyelitis virus) isolated in 1962; and (5) the PDCoV (porcine deltacoronavirus) described in 2012. The first two, TGEV and PRCV, belong to the Alphacoronavirus 1 species together with closely associated CoVs of cats and dogs, and PEDV and human CoVs (229E and NL63) form distinct species in the Alphacoronavirus genus. PHEV and PDCoV belong to the Beta- (Betacoronavirus 1 species) and Deltacoronavirus genera, respectively. PDCoV is closely related to the deltacoronaviruses from Asian leopard cats and Chinese ferret badgers (Ma et al. 2005). While PRCV induces primarily subclinical infections in pigs, enteropathogenic swine alphacoronaviruses (TGEV, PEDV, SeCoV, porcine enteric alphacoronavirus) and PDCoV are allied with a severe enteric disease of variable severity depending on the animal age and immune status. One serotype is recognised for each swine CoV species.

Fig. 4.1
figure 1

Phylogenetic tree of porcine coronaviruses of the Alpha-, Beta- and Deltacoronavirus genera. Closed circles indicate potential ancestral non-porcine coronaviruses. Bootstrap** with 1000 replicates was used to determine the reliability of each node

Full size image

TGEV and PEDV have been reportedly co-circulating in Eurasia and the USA. Recently in Europe, a pathogenic recombinant TGEV/PEDV variant (swine enteric coronavirus, SeCoV) was recognised and described (Akimkin et al. 2016; Belsham et al. 2016; Boniotti et al. 2016). SeCoV that contains PEDV S protein on a TGEV backbone apparently leads to disease clinically indistinct from the TGEV- and PEDV-produced ones (Table 4.1). Additionally, a novel bat-HKU2-like porcine coronavirus [porcine enteric alphacoronavirus (PEAV), GDS04 strain] associated with severe diarrheal disease in suckling piglets was identified in Southern China in 2017 (Gong et al. 2017) (Table 4.1). However, its prevalence and adaptation status to the swine host are unknown.

Table 4.1 Comparative pathogenesis of porcine enteric CoVs
Full size table

Currently, PHEV, the only porcine betacoronavirus, has a worldwide prevalence (Li et al. 2016). In neonatal piglets devoid of maternal antibodies (generally in those purchased from infection-free herds), PHEV causes either encephalomyelitis or a condition characterised by vomiting and wasting. Generally, maternal immunity protects piglets which have taken colostrum for up to 15 weeks, while in pigs older than 3–4 weeks and adult swine the infection is mostly subclinical. Therefore, it is seldom considered to be of economic importance. However, a recent report of an uncommon respiratory (influenza-like) presentation and increasing prevalence of PHEV in adult exhibition swine in the USA (Lorbach et al. 2017) may indicate a potential tropism shift that could lead to a substantial change in its epidemiology. To clear this complex epidemiological position, continuing monitoring and development of state-of-the-art rapid and reliable tools and techniques are needed to confirm and provide a clear differential diagnosis (Kim et al. 2001; Masuda et al. 2016).

CoVs are enveloped and pleomorphic, 60–160 nm in diameter. Swine CoV shaves single-stranded, polyadenylated, large genomic RNA (25–30 kDa) of positive-sense polarity that is infectious. The genome profile, replication strategies as well as protein expression match to other human and animal CoVs (Enjuanes and Van der Zeijst 1995; Gonzalez et al. 2003; Laude et al. 1993). Most porcine CoVs have four basic structural proteins: a large surface glycoprotein (S, spike protein that forms a monolayer of club-shaped spikes defined as the corona); a small membrane protein (E); an integral membrane glycoprotein (M); and a nucleocapsid protein (N). However, PHEV contains a haemagglutinin-esterase (HE) protein that forms a second shorter layer of surface spikes (de Groot et al. 2008). TGEV, PEDV and PDCoV also transcribe 1–2 accessory proteins encoded by open reading frame (ORF)3 (TGEV and PEDV), ORF6 (PDCoV), and ORF7 (TGEV and PDCoV). The complete genome organisation is 5′UTR-ORF1ab, S, ORF3, E, M, ORF6, N and ORF7-3′UTR.

An overall nt and amino acid sequence similarity of 96–98% among TGEV and PRCV proposes that PRCV evolved from TGEV. Two characteristic features of the PRCV genome that may account for its altered tissue tropism include a large omission (621–681 nt) in the N-termini of the S gene resulting in a reduced S protein size and variable sequence changes in the ORF3 (Ballesteros et al. 1997; Sanchez et al. 1999).

While there is no evidence of the existence of different PEDV serotypes (Lin et al. 2015a), genetically, PEDV strains are classified into two groups: (1) classical (isolates from Eurasia that are genetically similar to the prototype CV777 strain) and (2) emerging PEDV strains (Lin et al. 2016; Vlasova et al. 2014). All classical PEDV strains contain inserts and omissions in the spike gene (S INDEL) that are not present in the majority of the highly virulent emerging PEDV strains (Vlasova et al. 2014). Thus, these highly virulent strains that originally emerged in China in 2010 and transmitted to the USA, Europe and other Asian parts are referred to as emerging non-S INDEL PEDV strains. Recombinants between these two major groups of PEDV contain a set of deletions-insertions in their spike gene identical to those of the classical strains. They are called S INDEL strains and circulate in Asia, Europe and the USA. Additionally, a few reports described other uncommon PEDV variants that bear large deletions (194–216 aa) in the N-terminal domain (NTD) of the S protein and designated as S1 NTD-del type of PEDV (Diep et al. 2017; Oka et al. 2014; Suzuki et al. 2015). Unlike the altered tissue tropism from enteric TGEV to respiratory PRCV, these (S INDEL and S1 NTF have been reported-del) PEDV strains have kept their enteric predilection, but with lower virulence (Suzuki et al. 2016; Hou et al. 2017).

Swine enteric CoVs (TGEV, PEDV and PDCoV) are highly contagious and are associated with severe disease forms such as diarrhoea and vomition, and increased mortality in young ones (often 100%). They can cause sporadic outbreaks (endemic) or large-scale epidemics in swine-producing countries (Fig. 4.2). No specific treatments are available for any of the swine enteric CoVs that so far have resisted eradication efforts in different geographic regions. In this chapter, we have reviewed the diseases due to CoVs that continue evolving in domestic and wild swine, as well as another possible reservoir (avian or bat species) or secondary hosts including carnivores, or via the interspecies spread, recombination and generation of deletion escape variants. We also review PRCV that has lost its enteric tropism but is capable of inducing protective immune responses against TGEV that altered its global epidemiology.

Fig. 4.2
figure 2

Different stages of evolution of swine enteric coronaviruses

Full size image

4.2 Pathogenesis and Clinical Signs

4.2.1 TGEV

Extensive necrosis of mature enterocytes of jejunum and ileum within 24 h after infection results in reduced enzymatic activity (alkaline phosphatase, lactase, etc.), disrupted digestion, and cellular electrolyte (including sodium) balance. These changes primarily lead to the deposition of fluid in the intestinal lumen, acute malabsorptive diarrhoea (Moon 1978). The loss of extravascular protein and copious dehydration in piglets can be fatal (Butler et al. 1974). The latter can also lead to metabolic acidosis and hyperkalaemia, causing abnormal cardiac function.

TGE gross lesions are limited to the gastrointestinal tract. The distension of the stomach and the small intestine are seen to be filled up with curdled milk and sometimes petechial haemorrhages are visualised (Hooper and Haelterman 1966a). The small intestinal wall is thin and transparent. The villous atrophy in the jejunum and lesser in the ileum regions are the major TGE lesions and are more pronounced in neonatal pigs than in ≥3-week-old piglets (Moon 1978; Hooper and Haelterman 1966b). The increased severity of TGEV infection results in higher mortality (often 100%) in piglets less than 2 weeks of age that decreases in older pigs (Table 4.1). Although swine of any age is susceptible to TGEV, the mortality in TGEV seropositive groups and swine more than 5 weeks of age is usually low. Mechanisms that represent age-dependent susceptibility to clinical ailment comprise the slower substitution of tainted villous epithelial cells with newly differentiated enterocytes migrating from crypts in newborn pigs (Moon 1978). These lesions are similar to PEDV/PDCoV (Debouck et al. 1981; Jung et al. 2015a) lesions, but more severe than those caused by rotavirus (RV) (Bohl et al. 1978). Pathologic observations and degree of villous atrophy are exceptionally variable in pigs from endemic herds (Pritchard 1987).

Lungs (alveolar macrophages) and mammary gland tissues are recognised extra-intestinal sites for TGEV replication (Kemeny et al. 1975). Hitherto report shows pneumonia due to oronasal infection of pigs with TGEV (Underdahl et al. 1975), and the clinical significance of mammary gland infection is imprecise. However, agalactia is frequently observed in TGEV-affected sows, and TGEV spreads quickly among the population.

4.2.2 PRCV

PRCV replicates efficiently in porcine type 1 and 2 pneumocytes and is seen in epithelial cells of the nares, trachea, bronchi and bronchioles, and alveoli, and on occasion in alveolar macrophages (Atanasova et al. 2008; Pensaert et al. 1986; O’Toole et al. 1989). It can be noticed in blood and tracheobronchial lymph nodes. After experimental infection, nasal PRCV shedding usually lasts for 4–6 days. Pulmonary lesions and clinical signs subside consequently with an increase in the virus-neutralising (VN) antibody titres (Atanasova et al. 2008). Although PRCV is sometimes found in enterocytes, it does not spread efficiently to adjacent epithelial cells (Cox et al. 1990), and faecal shedding is low or undetectable.

PRCV predominantly causes upper and lower respiratory tract disease. The lesions appear to include lung and bronchointerstitial pneumonia, with regular peribronchiolar and perivascular lymphohistiocytic handcuffing (Atanasova et al. 2008; Cox et al. 1990; Halbur et al. 1993; Jung et al. 2007). The PRCV-induced bronchointerstitial pneumonia results in (1) thickened alveolar septa due to macrophage and lymphocyte infiltration, (2) hypertrophy and hyperplasia of type 2 pneumocytes, (3) aggregation of cell debris and inflammatory leukocytes in alveolar and bronchiolar lumina because of airway epithelial necrosis and (4) peribronchiolar or perivascular lymphohistiocytic inflammation.

4.2.3 PEDV

Clinical signs are evident between 22 and 36 h postinfection and match with the peak of viral replication (Table 4.1). The clinical presentation (watery malabsorptive diarrhoea, vomiting, depression and anorexia) and pathological lesions of PEDV are clinically indistinguishable from those of TGEV (Debouck et al. 1981; Coussement et al. 1982).

Morbidity is nearly 100% in piglets and variable in sows. Neonates below 1 week of age often die due to severe dehydration, and mortality touches 50–100%, whereas mortality is low in older pigs and they recover within a week. In sows, severity of diarrhoea is constant and frequently shows only depression and anorexia. Similarly, fattening pigs may develop watery faeces and can become anorexic and depressed within a week. As with TGEV, slower enterocyte turnover and immature innate immune system may add to the more extreme clinical signs, higher mortality and slower recuperation in PEDV-tainted piglets in contrast to weaned pigs (Jung et al. 2015a; Moon et al. 1975; Annamalai et al. 2015).

Each outbreak generally lasts for ~3–4 weeks; however, it might be longer on large breeding farms with multiple, isolated units and variable levels of lactogenic immunity in gilts/sows. PEDV-exposed pregnant sows can provide sufficient lactogenic immunity to protect their piglets, and PED outbreaks stop. After the passage of acute outbreak, diarrhoea may persist and is recurrent in weaned pigs, resembling endemic TGE form (Martelli et al. 2008).

The severity of lesions and the virus replication levels in naturally and experimentally infected suckling piglets vary for classical PEDV, emerging non-S INDEL and S INDEL PEDV strains (Jung et al. 2015a; Coussement et al. 1982; Kim and Chae 2003; Pospischil et al. 1981; Sueyoshi et al. 1995; Lin et al. 2015b; Madson et al. 2014). Lesions remain localised to the small intestine that is swollen and filled up with watery, yellowish liquid. Microscopic examination shows syncytia, vacuolation and shedding of small intestinal enterocytes primarily on the proximal villi. Similar to TGEV, PEDV infection results in degeneration of enterocytes that reduces the villous height:crypt depth (VH: CD) ratios and the enzymatic activity. Although PEDV antigens were detected in colonic epithelial cells, no associated histopathologic changes have been observed (Debouck et al. 1981).

Viral RNA has been confirmed in the serum, and different tissues (including lung, spleen, liver and muscle) of pigs euthanised during PEDV infection (Suzuki et al. 2016; Jung et al. 2014, 2015a; Lohse et al. 2017; Chen et al. 2016a; Park and Shin 2014) with high RNA titres in the serum of 7–8 log10 GE/mL coinciding with peak RNA titres in faeces (11–12 log10 GE/mL) (Jung et al. 2015a). Additionally, PEDV RNA is identified in 40.8% (20/49) of sow milk samples during the epidemics caused by emerging PEDV strains (Sun et al. 2012).

4.2.4 PDCoV

The clinical signs are observed within 1–3 days after PDCoV infection in suckling and older pigs. Although clinical symptoms are similar (Table 4.1), they are less pronounced compared to PEDV and TGEV infections (Chen et al. 2015; Hu et al. 2016; Jung et al. 2015b; Ma et al. 2015). They include acute, watery diarrhoea due to malabsorption induced by the massive loss of absorptive enterocytes. Additional signs may include vomiting, dehydration, weight loss, lethargy and death. Vacuolation of the infected colonic epithelial cells may inhibit water and electrolyte reabsorption. The seronegative pigs are susceptible to PDCoV infection at any age, with high morbidity that can reach 100% in piglets. Evaluation of filed cases in the USA, China and Thailand in 2014 shows that PDCoV infection is associated with up to 40–80% mortality among suckling pigs (Anon 2014). The infection on breeding establishments remains self-limiting and stops when pregnant sows develop lactogenic immunity adequate to secure their offspring.

Gross lesions include thinned and transparent intestinal walls (jejunum to the colon) with a collection of a lot of yellow liquid with gas. Often stomach is found bloated with curdled milk.

PDCoV replicates in the epithelial cell of the large and small intestine. Lesions look like those seen in TGEV and PEDV infections but are mild (Chen et al. 2015; Hu et al. 2016; Jung et al. 2015b; Ma et al. 2015). Histological findings are intense, multifocal to diffuse, mild to extreme atrophic enteritis of jejunum and ileum, at some point joined by mild vacuolation of caecal and colonic epithelial cells (Jung et al. 2015b). Amid acute infection, PDCoV antigens are available in the villous epithelium of the mid-jejunum to the ileum and a lesser degree, in the duodenum, and caecum/colon (Jung et al. 2016a). PDCoV antigens may also be noticed in immune cells of the intestinal lamina propria, Peyer’s patches and mesenteric lymph nodes (Hu et al. 2016). Inflammatory cell (macrophage, lymphocyte and neutrophil) infiltration can be observed in the lamina propria. Acute necrosis of PDCoV-infected enterocytes (Jung et al. 2016a) results in marked villous atrophy in jejunum and ileum, but not duodenum or large intestine, which coincides with fewer PDCoV antigen-positive duodenal, caecal or colonic epithelial cells (Chen et al. 2015; Jung et al. 2015b). Acute-phase viremia with low PDCoV RNA titres in serum is observed (Chen et al. 2015; Hu et al. 2016). After recovery of pigs from clinical disease, huge amount of PDCoV antigens are found in the gut lymphatic tissues (Hu et al. 2016). Additionally, low or moderate quantities of PDCoV RNA, but not antigens, are detected in multiple organs, feasibly as of viremia (Chen et al. 2015; Ma et al. 2015; Jung et al. 2016b). Decreased levels of PDCoV shedding (compared with PEDV and TGEV) in the faeces may be indicative of its incomplete adaptation to pigs and can contribute to its slower spread among swine herds and the lower mortality of nursing pigs (Jung et al. 2015b).

4.3 Incidence and Prevalence of the Disease

4.3.1 TGEV

TGEV was first detected in the USA in 1946 from outbreaks of acute diarrhoea with high mortality in piglets (Doyle and Hutchings 1946). Since then the disease has been reported in several pig-rearing countries practicing intensive pig farming system, including Europe, Asia (Japan, Korea, Malaysia and Taiwan), the Americas (North, Central and South) and Africa (Zaïre, Ghana). Despite the widespread application of vaccines, TGEV infections were a prime reason for enteric disease and mortality in piglets in the USA and globally in the 1960s–1980s. The presence and extensive prevalence of PRCV, a deletion mutant of TGEV, narrowed the clinical impact of TGE (Laude et al. 1993; Pensaert et al. 1986, 1993; Brown and Cartwright 1986; Pensaert 1989; Yaeger et al. 2002). Currently, sporadic outbreaks of profuse diarrhoea in piglets due to TGEV in TGEV/PRCV seronegative herds are yet to be confirmed in North America, Europe and Asia. However, careful differentiation between TGEV and emerging TGEV/ PEDV recombinants may be needed.

Two epidemiologic forms of TGE are apparent: epidemic and endemic. Epidemic TGE noticed transcendently in seronegative flocks. After entry, the illness transmits quickly to swine of any age, particularly in winters, with inappetence, vomition or diarrhoea in affected animals. Suckling pigs exhibit prominent clinical signs and get quickly dehydrated. Lactating sows usually show anorexia and agalactia, with reduced milk production, which further adds to piglet mortality.

Endemic TGE indicates the persistence of the virus and disease in a group perpetuated by the continuous influx of susceptible swine. It is a classic sequel to a primary outbreak and occurs in seropositive animals that regularly have farrowing (Stepanek et al. 1979), additions of the herd or mixing of susceptible pig population. In endemic groups, TGEV spreads slowly among grown-up pigs (Pritchard 1987). Sows are most of the time resistant and asymptomatic and will transfer a variable level of passive lactogenic immunity to their offspring. In these groups, mild TGEV diarrhoea is seen with mortality under 10–20% in pigs from ~6 days of age until ~2 weeks post-weaning.

4.3.2 PRCV

PRCV infects the respiratory tract with limited or no shedding in faeces (Pensaert 1989). The first isolation of PRCV was from Belgium in 1984 (Pensaert et al. 1986) and 1989. PRCV was detected in the USA in the herds without a prior history of TGEV infection or vaccination (Hill et al. 1990; Wesley et al. 1990). Antibodies produced in PRCV-infected pigs neutralise the TGEV.

Since the first report, the virus has been introduced rapidly in Europe (Laude et al. 1993; Brown and Cartwright 1986; Have 1990; van Nieuwstadt et al. 1989) and attained endemic status worldwide, including entering TGEV-free countries (Laude et al. 1993; Pensaert 1989; Pensaert et al. 1993). A serological survey from the USA in 1995 demonstrated that clinically healthy pigs from different herds were found to be seropositive for PRCV (Wesley et al. 1997) in Iowa State.

4.3.3 PEDV

The classical PEDV strains were the cause of several epidemics with heavy mortality in Europe from 1971 until the late 1980s. However, after 2000, reports are very rare. In Italy, an epidemic involving 63 herds occurred in 2005 and 2006 where pigs of all ages were found affected, but mortality was mainly limited to suckling piglets (Martelli et al. 2008). Because of the low clinical importance of the disease, no surveillance studies were conducted until the emergence of new PEDV variants in Europe in 2014. Note that the historical prevalence of classical PEDV in the European swine population is unknown. An emerging non-S INDEL strain led to an outbreak in Ukraine in 2014; while outbreaks in European countries (Germany, Belgium, France, the Netherlands and Slovenia) were confirmed as of S INDEL strains (Lin et al. 2016).

Infections associated with classical PEDV strains were originally reported in China in the late 1970s. Since then, PED has spread among swine farms and became leading cause of viral diarrhoea, despite the use of vaccines (targeting the prototype PEDV strain CV777) (Wang et al. 2016a; Xuan et al. 1965). Likewise, housefly (Musca domestica) is also proposed as a mechanical vector for TGEV (Pilchard 1965). TGEV antigen is seen in flies on a swine herd and TGEV shedding up to 3 days from experimentally feeding flies (Gough and Jorgenson 1983). Notably, surveys done in Central Europe confirmed the presence of TGEV antibodies in nearly 30% of the feral pigs (Sedlak et al. 2008). Although TGEV shedding is detectable for up to 104 dpi (Underdahl et al. 1975), it is undefined yet whether infectious virus particles are shed or transmitted at that time. Adding of sentinel pigs to a herd at 3, 4 and 5 months after a past TGE outbreak resulted in no new disease in the introduced pigs (Derbyshire et al. 1969).

4.6.2 PRCV

Swine population density, farm distances and seasons influence PRCV epidemiology (Pensaert 1989; Have 1990). Pigs get PRCV infection at any age through contact or airborne transmission. The risk of spreading PRCV increases in zones of high swine density, where the virus can journey several miles.

4.6.3 PEDV

As for other enteric viral infections, in PEDV also direct or indirect faecal-oral transmission is the main route of virus transmission. Acute outbreaks in non-immune farms often occur within 4–5 days after newly purchased pig arrival. The virus enters farms mostly via infected pigs, but also by contaminated feed, trucks, boots or other fomites. Farm workers may also act as a vehicle for virus transmission to naïve pigs (Dee et al. 2014, 2016; Schumacher et al. 2016). Evidence of PEDV aerosol transmission is reported in some (Alonso et al. 2014) but not other studies (Niederwerder et al. 2016). In four-week-old pigs infected with emerging non-S INDEL PEDV strain, infectious virus excretion lasted for 14–16 days (Crawford et al. 2015). Nevertheless, a few pigs shed PEDV RNA, at 42 days post-initial oral exposure, but non-infectious virus particles were seen in faeces.

Similar to TGEV, after initial outbreaks on the breeding farms, PEDV can become endemic if sufficient litters of pigs are produced and weaned, allowing maintaining the virus. Of note, a report from South Korea showed 9.75% PEDV infection rate in wild boars (Lee et al. 2016b), although their role in maintenance and transmission of PEDV is unclear.

4.6.4 PDCoV

The main method of PDCoV transmission is the faecal–oral route. Faeces, vomit and other contaminated fomites are the major sources of the virus. Experimentally induced PDCoV diarrhoea lasted for ~5–10 days, with faecal virus RNA shedding lasting for up to 19 days (Hu et al. 2016; Ma et al. 2015). Pigs generally continue shedding PDCoV RNA in the faeces after recovery from disease; therefore, another possible reservoir for PDCoV may be subclinically infected or convalescent carriers.

4.7 Prevention and Control

4.7.1 TGEV

Treatment of clinically affected newborn piglets is usually ineffective in field situations; however, electrolyte/glucose solution supplementation of piglets that are 1 week or older may reduce their mortality (Bohl 1981). Extra heat, deep bedding and antibiotic solutions (to treat secondary infections) generally can improve piglet health.

Enhanced biosecurity measures should be maintained to decrease a chance of introduction of infected animals, and contaminated vehicles from TGEV-affected farms to susceptible herds. TGEV infection can be spread not only with infected live animals but also with unprocessed tissues of slaughtered TGEV-infected animals (Forman 1991).

Many methods for immunising sows to induce lactogenic immunity and consequent protection of neonatal piglets have been attempted (Chattha et al. 2015; Saif and Jackwood 1990; Bohl and Saif 1975). Several viral vaccines (virulent, attenuated, inactivated and recombinant subunit) with different routes of administration (oral, intra-nasal, subcutaneous, intramuscular and intra-mammary) (Saif and Sestak 2006; Moxley and Olson 1989) have been evaluated in the past. To note, intramuscular, parenteral or intra-mammary administration of pregnant sows with live attenuated, inactivated or subunit vaccines did not offer complete protection but were found to be effective to reduce piglet mortality rates (Brim et al. 1994). Unlike natural intestinal infection with the virulent virus, attenuated viruses do not stimulate the gut-MG-sIgA axis sufficiently for the induction of immunity similar to that observed following this. There are two commercial vaccines based on a live-modified TGEV strain for combined oral-intramuscular administration produced by Merck Animal Health: PROSYSTEM® TGE/Rota and PROSYSTEM® TREC. These vaccines can effectively stimulate a response in previously exposed pigs, but do not protect the naïve population.

Herd immunity can be enhanced by exposing all the sows to virulent TGEV (using intestinal contents or gut tissues of affected pigs) to boost lactogenic (milk) immunity (Bohl and Saif 1975; Bohl et al. 1972). This practice is called feedback and results in the rapid development of immunity in pregnant sows (particularly in those due to farrow 2 weeks or more after the start of the outbreak) and reduces losses in newborn piglets. However, it may also result in dissemination of other pathogens (potentially present in TGEV-containing faeces/intestinal contents) to adjacent herds. On small-scale farms, herd immunity is accomplished, and TGEV infection is self-limiting. In contrast, in larger farms (≤200 sows) with a continuous farrowing system and continual influx of susceptible animals, TGEV infection frequently becomes endemic after the primary outbreak (Saif and Sestak 2006). Elimination of endemic TGE in a herd can be attempted using the feedback method. After this is done, no weaning of piglets should occur during the following 3–4 weeks so that there remains no susceptible host in the herd while TGEV is circulating on the farm.

4.7.2 PEDV

Due to the lack of PEDV-specific antivirals, the treatment is focused on alleviating the diarrhoeal disease. PEDV-infected pigs must get enough water to reduce dehydration, which exacerbates the severity of the disease. Temporary withholding of feed may benefit fattening pigs during the acute stage of the disease.

As in the case with TGEV, appropriate biosecurity measures should be applied to avoid the introduction of PED onto farms. Present epidemiological knowledge indicates that virus is spread between farms mainly through animal and human traffic, and contaminated feed (https://www.aphis.usda.gov/animal_health/animal_dis_spec/swine/downloads/secd_final_report.pdf). Careful disposal of the dead stock is recommended.

In contrast to the present situation in Asia, in Europe, PEDV infection (with mostly mild S INDEL strains in circulation) is considered to be of marginal economic importance and therefore does not warrant the development of a vaccine (Lee 2015). However, severe classical PEDV outbreaks in Asia have necessitated the development of PEDV vaccines to prevent and control the infection. In China, the CV777-based inactivated and attenuated PEDV vaccines were approved in 1995 and 1998, respectively (Wang et al. 2016b). Soon after, attenuated vaccines based on classical PEDV strains KPEDV-9 and DR13 were commercialised in 1999 and 2004, respectively, in Korea (Kweon et al. 1999; Song et al. 2007). Since 1997 a commercial attenuated PEDV vaccine based on cell culture-adapted classical PEDV P-5V strain (Nisseiken Co. Ltd., Japan) is administered to sows in Japan (Sato et al. 2011). These vaccines based on classical PEDV strains appeared to satisfactorily control PED in Asia until the highly virulent non-S INDEL PEDV strains have emerged (Lee 2015). As demonstrated in the field, the classical PEDV vaccines have failed to protect pigs from severe diarrhoeal disease associated with the emerging highly virulent non-S INDEL PEDV strains (Lee 2015).

The deliberate exposure of pregnant sows (feedback method) to PEDV promotes the rapid development of lactogenic immunity and thus shortens the course and the severity of the disease on the farm (Chattha et al. 2015). However, as mentioned in the TGEV section, this method may contribute to the spread of other infectious agents throughout the farm. We have recently demonstrated that high dose of virulent PEDV administered to sows can substantially increase their piglet survival rate as compared to low-dose and mock-infected sows (Fig. 4.3) (Langel et al. 2016). This novel finding suggests that the current feedback-based control strategies can be improved by ensuring the uniform administration of high-dose PEDV to pregnant sows.

Fig. 4.3
figure 3

Mucosal immune responses and lactogenic immunity may be influenced by PEDV dose given to pregnant swine. Gilts received high and high, low PEDV dose or mock at 3–4 weeks prepartum. All piglets were PEDV-challenged at 3–5 days post-partum (Langel et al. 2016)

Full size image

Since the outbreaks of 2013, the USA has conditionally licensed two PEDV vaccines targeting emerging non-S INDEL PEDV strains: alphavirus-based vaccine (Harris vaccinesâ„¢, now Merck Animal Health) and an inactivated vaccine (Zoetis) (2014). The first vaccine was developed in June 2014 using a replication-deficient Venezuelan equine encephalitis (VEE) virus packaging system expressing the S protein of an emerging non-S INDEL PEDV strain (Crawford et al. 2016). The second vaccine developed in September 2015 was an inactivated whole-virus (non-S INDEL PEDV) vaccine plus an adjuvant (Crawford et al. 2016). In October 2016, an inactivated vaccine based on non-S INDEL PEDV strain AJ1102 was licensed in China (Wang et al. 2016b). In South Korea, an inactivated vaccine candidate based on non-S INDEL strain KNU-141112 was demonstrated to be protective in sows and their suckling piglets (Baek et al. 2016). However, the efficacy of these vaccines/vaccine candidates in the field is not assessed. To date, reverse genetics platforms have been generated for both classical and emerging non-S INDEL PEDV strains using different approaches (Beall et al. 2016; Jengarn et al. 2015; Li et al. 2013) and can be used for the future rational design of safe and effective PEDV vaccines.

4.7.3 PDCoV

The disease-preventive measures adopted for TGEV and PEDV control and prevention can be useful for PDCoV infection too. In the absence of any suitable vaccines or antivirals to control PDCoV disease, reliable regime includes symptomatic action giving bicarbonate liquids and ad lib water to alleviate acidosis and dehydration in suckling pigs. Antibiotics administration may be beneficial in the case complicated by concurrent/secondary bacterial infection. In the event of heavy mortality, feedback techniques must be opted to stimulate lactogenic immunity and reduce mortality. Additionally, during PDCoV epidemics, a strict biosecurity plan must be implemented to lessen PDCoV spread via infected fomites. The systems all in/all out and thorough disinfection (using phenolic disinfectants, bleach, peroxides, aldehydes or iodophors) can break the disease cycle.