Porcine Proliferative Enteropathy: Etiopathogenesis and Prevalence

1. Introduction

Porcine proliferative enteropathy (PPE) is a highly endemic bacterial enteritis caused by Lawsonia intracellularis, posing a significant global concern [1]. This enteric disease is characterized by adenomatous proliferation of immature intestinal epithelial cells in the distal small intestines and has been a serious issue on pig farms worldwide [2]. Its economic burden is substantial, with herd-level prevalence ranging from 48% to 100% at swine production sites globally [3]. Farm prevalence studies in Europe, Asia, and Northern America have indicated that 24 to 47% of pig farms had a serious incidence of PPE in recent years [4]. Informed estimates of economic losses, using specific production data and disease diagnostic information, have ranged from an annual loss of 4 million GB pounds to the British industry and a staggering US $ 98 million to the United States industry [5].
L. intracellularis is a Gram-negative, non–spore–forming, microaerophilic, curved-shaped rod that is obligately intracellular [6]. The bacterium is 1.25 to 1.75 mm long, 0.25 to 0.43 mm in width, and exhibits a trilaminar outer envelope [7]. It is like a tiny, living torpedo, with a unipolar flagellum that propels it extracellularly in cultivated organisms, demonstrating darting motility in vitro upon escape from infected enterocytes [8]. Besides swine, L. intracellularis infects many species of domestic and wild animals, including horses, hamsters, rabbits, foxes, deer, ferrets, ostriches, and nonhuman primates [9].

2. Transmissions

The transmission dynamics of PPE involve a complex interplay of factors, including fecal shedding, pig-to-pig contact, and environmental contamination [10]. The high shedding rates of L. intracellularis in feces and its prolonged environmental survival create favorable conditions for intra-herd transmission [11]. Pigs clinically affected with PPE can shed at least 3 × 108 L. intracellularis per gram of feces, so less than one gram of infected feces is required to infect naive pigs [12,13]. The infection of a single pig within a group or pen is likely to result in the infection of susceptible pigs in contact, as sentinel pigs became infected 8 days after they were housed in contact with pigs inoculated with 105 of L. intracellularis [14]. Furthermore, some studies have shown that L. intracellularis can survive in feces in contaminated pig pens for at least 2 weeks at temperatures between 9°C and 18°C [12,13]. Therefore, the combination of pigs shedding large numbers of bacteria in feces, the prolonged survival of the bacteria in the environment, and the small doses required to initiate an infection strongly favor the transmission of infection within the herd [15].

Environmental contamination also plays an essential role, with contaminated surfaces acting as reservoirs for L. intracellularis [16]. Some investigations indicated that slatted and meshed flooring were significant risk factors for PPE [17,18]. These results suggested that insufficiently cleaned floors are commonly found in postweaning facilities, which may increase the infection rate of L. intracellularis in herds [18]. Furthermore, rodents may further cause transmission of L. intracellularis within swine populations [19]. Previous studies have demonstrated L. intracellularis infection and proliferative enteropathy in rodents, which are external vectors that cannot be ignored in pig farms [12,20]. Farm management practices, such as swine grouping, feed management, stocking density, and hygiene, significantly influence the risk of infection [21]. All-in-all-out management systems and proper hygiene protocols, including thorough cleaning and disinfecting of pens between pig groups, are essential for preventing transmission [22,23]. For instance, previous research observed the risk of L. intracellularis infection was six times greater in a continuous flow management pig production system when compared to an all-in-all-out management program [24].

3. Infection mechanisms

The infection mechanism of PPE involves several key steps:

3.1  Ingestion of Contaminated Material: Pigs become infected by ingesting food or water contaminated with feces containing L. intracellularis [8].
3.2  Entry into the Intestinal Epithelial Cells: After ingestion, L. intracellularis penetrates the cells lining the intestinal mucosa, primarily the epithelial cells of the ileum (the last part of the small intestine) [25]. L. intracellularis preferentially adheres to the immature epithelial cells and then multiplies and spreads in these cells as they divide [26].
3.3  Proliferation and Localized Infection: Within the infected epithelial cells, L. intracellularis multiplies, causing damage to the host cell and inducing changes in its structure and function [27]. This proliferation leads to the formation of characteristic microscopic lesions, resulting in crypt hyperplasia in the intestinal mucosa, where there is an abnormal increase in the number of cells in the intestinal crypts [28].
3.4  Symptoms occur: Infected epithelial cells with L. intracellularis are characterized by the lower expression of apical membrane transporters involved in nutrient acquisition [6]. Excessive non-absorbed solutes in the intestinal lumen result in osmotic/malabsorptive diarrhea.

4. Clinical symptoms

Porcine proliferative enteropathy can manifest in two distinct clinical presentations: chronic diarrhea and stunted growth in growing-finishing pigs, known as porcine intestinal adenomatosis (PIA), or acute hemorrhagic diarrhea leading to mortality in gilts and finishing pigs close to market age, referred to as proliferative hemorrhagic enteropathy (PHE) (Figure 1) [8]. Besides, based on morphological properties, four forms of porcine ileitis are recognized in pigs: (1) PIA, (2) necrotic enteritis (NE), (3) regional ileitis (RI), and (4) PHE (Figure 2) [2]. Of these, PIA is considered to be the uncomplicated, chronic form, NE is considered to be due to secondary infection superimposed on PIA, RI is considered to be the recovery stages of NE, and PHE is regarded as the acute form of the ileitis [29].

Figure 1. Porcine small intestine. (1a): Proliferative hemorrhagic enteropathy (PHE). Observe mucosa thickened and blood in the lumen (arrow). (1b): Porcine intestinal adenomatosis (PIA), with marked thickening of intestinal mucosal with small reddening area (circle) [15].

Figure 2. Porcine proliferative enteropathy classification. (organized from [30])

The acute presentation of PHE, a severe form of PPE, primarily affects adult pigs between 4 and 12 months of age [31]. Typical symptoms can include acute diarrhea of varying severity, often accompanied by occasional black tarry feces, which may progress to watery diarrhea with frank blood [32]. Pallor, weakness, and rapid death are common observations, particularly in severe cases, leading to mortality rates as high as 50% [33,34]. Notably, pregnant sows may experience abortion following infection [35]. While some cases progress rapidly to death, others may exhibit sudden death without preceding symptomatic signs [36]. The chronic form of PIA commonly affects weaners and growers and is observed as persistent chronic diarrhea but can cause mortality [29]. The symptoms of PIA present reduced weight gains and nonuniformity (Figure 3) in weight among 6 to 12-week-old pigs. Pigs with PIA can also progress to NE, which can lead to death [37]. Necrotic enteritis destroys mucosa, resulting in extensive coagulative necrosis of the epithelium, with yellowish-grey lesions on the mucosal surface [38]. The pigs that survive this NE episode may progress to RI, a progressive granulation tissue proliferation in the lamina propria and submucosa [8].

Figure 3. The chronic form of proliferative enteropathy was confirmed in these uneven pigs by identifying gross and histologic lesions (excerpted from [39]).

Additionally, subclinical enteritis may manifest as variations in pig size, sporadic diarrhea, decreased growth rates, and potential signs of anorexia and apathy [40]. Monitoring individual weight gain can aid in the early identification of subclinical infections, helping to mitigate potential economic losses. It is crucial to differentiate PPE from similar pathologies such as swine dysentery, salmonellosis, and porcine intestinal adenomatosis, which also present with hemorrhagic diarrhea [41]. Despite the variability in clinical presentation, the subclinical form of PPE is considered the most common, posing challenges in detection due to the absence of overt clinical signs but still impacting production parameters adversely.

5. Prevalence

Many investigations from different countries show that PPE is an endemic disease widespread across every continent, and it is involved in pork production and occurs in many different production systems [3,42]. The prevalence of PPE is determined either by the use of L. intracellularis-specific serology assays, such as indirect immunofluorescence assay (IFA), indirect immunofluorescent antibody test (IFAT), or by molecular assays, such as the polymerase chain reaction (PCR) and nested PCR (nPCR) [43]. Reported herd prevalence in the countries varies from 6.7 to 93.7%, while the number of positive animals per herd (within-herd prevalence) ranges from 0.7 to 43.2% [3]. However, the influencing factors (e.g., age and diagnostic methods) should be considered when interpreting these values [44]. Table 1 lists some of the currently known results of European surveys [3]. The prevalence of L. intracellularis in feces (by PCR) has been reported to range from 20 to 75% in positive herds of large pig-producing countries such as the United States, Brazil, and Denmark [10,45,46]. However, 4.5%, 30%, and 37.6% of the herds in Spain, Taiwan, and Norway also tested as PPE positive, respectively [47-49]. Positive fecal PCR results usually indicate L. intracellularis presence, either currently or in the recovery stages, and high seroprevalence indicates that pigs were previously exposed to L. intracellularis. Serological analysis by IFAT or ELISA tests revealed that approximately 60 to 100% of farms in the United States, the European Union, and Australia were positive for L. intracellularis antibodies [43,50].

Table 1. Herd prevalence of L. intracellularis in total and per age category in different European countries was detected by PCR.

Age categories: Nursery pigs (NP): weaner - 25 kg; Growing pigs (GP): 25- 40 kg, Finishing pigs (FP): 40 kg – slaughter; and Sows (S).
Diagnostic methods: Enzyme-linked immunosorbent assay (ELISA), indirect Immunofluorescence assay (IFA), Polymerase chain reaction (PCR), and nested PCR (nPCR).

6. Summary

Table 2. Brief description of porcine proliferative enteropathy (sorted by Dr. Ko-Hua Tso)

7.  References

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