Etiology, pathogenesis and treatment of ileitis infections

Steven McOrist School of Veterinary Medicine and Science, University of Nottingham, United Kingdom

Porcine Proliferative Enteropathy (ileitis)

This comprises a group of conditions involving pathological changes in the ileum and lower small intestine associated with the bacterium Lawsonia intracellularis. This exists on most if not all farms. Infected faeces are the major vehicle for spread around the farm.

important difference in the tests for these surveys is that the PCR test positive indicates that the pig was a clinical case of ileitis, actively excreting the organism at the time of the test, but the serology test indicates that the pig has been exposed to positive ileitis faeces in the recent weeks before the sample was collected. There are some broad questions that arise from the data presented in Table 1. First, there is a very high level of infected farms across Asia. The widespread nature of the infection suggests that the disease is endemic on most farms, with many pigs presumably not showing obvious diarrhoea. In moderate-dose challenge-exposure studies, approximately a half of any group of challenged pigs do not go on to develop visible diarrhoea, but did suffer noticeable ileum lesions and poor growth performance. Possible carrier

inferred from the serologic data, have in fact suffered the infection, but failed to develop beyond a localized intestinal lesion.

Ileitis in China
In China, the data originated from three recent studies. In one study, 76% of 17 farms sampled near Shanghai were PCR-positive on faeces and ileum tissue. Over 65 percent of cases of diarrhoea and deaths in 2 to 4 month old pigs were positive by their PCR. In a second larger study, 1,650 blood samples were collected from 33 pig farms in 6 provinces and tested by ELISA. All of the pig farms tested (100%) were positive for ileitis. The infection was lowest in the weaner pig age groups, but increased steadily from pigs 13 weeks-old up to gilts, which had a high level of infection. These

Current prevalence in Asia

Prevalence data has been gathered from participating diagnostic laboratories and specific published references, illustrating a high level of infection in Asia, see Table 1. Independent studies have confirmed the >90% sensitivity and specificity of the IFAT and IPMA serologic assays used - these use Lawsonia antigen coated wells, with immuno-fluorescence or immunoperoxidase detection of bound antibody.

Table 1. Estimation of percentages of porcine proliferative enteropathy prevalence in surveys of farms and pigs in different countries, 2000-2004
Country China Japan Korea Malaysia Thailand The Philippines Vietnam USA Canada In some studies, the faeces PCR was also used, with Lawsonia-specific primers used to detect Lawsonia bacteria in DNA extracted from the faeces of pigs, usually pigs with diarrhoea. The Positive farms % 100 94 100 100 100 86 77 96 95 Positive pigs % 40-100 60 70 50 38 42 35 60 60 Number of farms tested 50 378 100 10 24 40 13 405 78

sites other than the lower intestine, such as the tonsils, are rarely infected, except in heavily infected pigs. This suggests that the numerous serologicpositive but apparently healthy pigs

studies confirmed ileitis as the most common cause of diarrhoea among pigs of this age in China.

in weaner pigs in commercial farms in Vietnam has been always a problem for pig producers.

Ileitis in Korea
Pig farming in Korea largely consists of well-run intensive farms. Recent specific studies of ileitis have looked at numerous pig farms in Korea. An initial study using the PCR test tested faeces samples from 35 farms in 6 provinces of Korea. Although this test has the lowest sensitivity of any current test, they found that up to 33% of farms were positive for ileitis. A more comprehensive survey using the sensitive and specific immunofluorescence assay investigated over 800 samples from 65 farms in the 6 provinces and found all 65 farms had at least one positive pig. On each farm, usually 50 to 60% of pigs were positive.

Ileitis in Thailand, Philippines, Malaysia

Limited local surveys have been conducted in all these countries, which are summarised in Table 1. In Thailand, Kasetsart University found that 100% of a total of 24 Thai farms tested positive for Lawsonia by serology and that an average of 38% of the pigs tested on those farms were positive. One 2,500 sow commercial Thai farm examined in detail had an average number of positive pigs from 11% at 8 weeks of age (early weaners) up to 39 % at 16 weeks of age (finishers). Only limited initial surveys have been reported from the Philippines and Malaysian farm groups. Data for the important pig industries of Burma, Indonesia, Laos and Cambodia is not available, but ileitis is certainly active in these countries also. The intensive Culindo pig farms at Bulan in Indonesia-Singapore (20,000 sows) have diagnosed many cases of ileitis in occasional pathology investigations.

and the resulting poor performance in pigs affected by either the subclinical or chronic form of PPE is an important form of economic loss. The subclinical form is merely harder to detect because poor performance is less apparent and there may be few actual runt pigs. Milder chronic cases and subclinical cases can be difficult to detect but can be relatively common in the group. Therefore, groups should be carefully inspected for apparent wasting of wellgrown pigs and for irregular cases of diarrhoea and runt pigs.

Epidemiology - the Spread of Chronic and Subclinical PPE

The chronic and subclinical forms of PPE are especially common on traditional, single-site, farrow-to-finish farms that have all farm buildings on one property. There is a simple flow of pigs and infected faeces around the farm, and the disease passes from one pig to the next. It is likely that Lawsonia can survive in pig faeces for around 2 weeks under normal farm conditions. Infected pigs often shed Lawsonia intracellularis for about 2 weeks after first infection but some 10% of pigs can shed it for many weeks. Ileitis is then spread when one pig contacts the faeces of an infected pig and ingests some of the L. intracellularis bacteria into its mouth and gut. The bacteria enter the wall of the pig intestine, start an infection and then multiply. Once the infection develops in the intestine, L. intracellularis re-enters the pig faeces and moves to the next pig. Since the incubation period is 2 to 3 weeks in most individual animals, a slow build-up of disease in a group can occur over a month or more after the disease is first introduced to one pig in the nursery or grower areas. In some infected pigs, however, there can be large numbers of L. intracellularis in the faeces, causing rapid exposure of many pigs among a group. Once one of them becomes infected, a more obvious outbreak occurs. Other vectors, such as birds or rodents, appear to have little influence on L. intracellularis infections on infected farms. On most farms, chronic and subclinical

Ileitis in Vietnam
Vietnam has 22 million pigs, mainly farmed in the Red River delta, which is the main pig production area in northern Vietnam. Intensive farms still only contribute around 20% of the total pork production in Vietnam, but these were the ones mainly selected for sampling in a recent study. Breeder farms consisted of 20 to 300 sows, with piglets usually sold to other weaner operations at 28 daysold. These operations often slaughtered pigs at only 35-40 kg for local or export markets. PCR detected Lawsonia in 30 out of 87 (34.5%) faecal samples, originating from 4 out of 7 (56.4%) intensive farms sampled. The prevalence of infection varied from 28.57 to 90% on these positive farms. In an outbreak of acute hemorrhagic enteropathy in breeding adult pigs from Hatay province, 90% were PCR-positive. Positive DNA was also detected in two samples submitted from small household-held pigs. Positive IgG antibodies against L. intracellularis were detected in sera of pigs in 77% of surveyed intensive farms. Only 3 farms had no positive serum samples at the time of testing. Within herd prevalence varied between 7 and 40%, with an average prevalence of 11.5%. Diarrhoea

Clinical Signs - Chronic and Subclinical Ileitis

On a typical pig farm affected with ileitis, clinical observations of chronic and subclinical cases of PPE generally include two main signs: one is diarrhoea and the second is reduced weight gain or variation in the weights of growing pigs, 6 to 20 weeks old. In the more severe chronic form, there is usually a measurable number of runted pigs. Diarrhoea and poor weight gain are often seen together in a group of pigs, but not necessarily in the same pigs. In affected pigs, diarrhoea is generally moderate. The stools are loose and pasty but normal in colour. In many cases, the faeces is sloppy and poorly formed, resembling cow faeces or wet cement. In more severe cases, the faeces may become more watery and have a liquid, sloppy texture. There may be some undigested feed material present. Reduced weight gain, feed efficiency

Chart 1 illustrates a typical group of pigs as they age from weaning to finisher age on a traditional, single-site farm in Asia. The chart measures the percentage of pigs in the group with positive ileitis antibody levels in their blood. Maternal antibodies are still present in some pigs at weaning, but disappear in all pigs one month after weaning. Serum antibodies rapidly appear again around 8 weeks after weaning because many pigs have become infected at 4 or 5 weeks post-weaning and developed fresh antibodies to infection.
100 90 80 70 60 50 40 30 20 10 0

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PPE occur after maternal antibody levels start to decline after weaning. Antibodies eventually reduce to a level where pigs become susceptible to L. intracellularis infection. This occurs at around 4 or 5 weeks old, and often coincides with the time that pigs are mixed into the farm nursery and in the early growing period. After the 2- to 3-week incubation period, some pigs develop disease, start to excrete the bacteria and spread it to other pigs. Infection occurs in many pigs after weaning and builds up in the grower and finisher areas. It then declines to a lower but detectable level in gilts and older breeding animals.

breeding animals to the group, isolating the animals in testing or breeding stalls, transporting the group on trucks and so on. Pigs can remain nave until they are older if they receive continuous antibiotic medication that reduces early exposure to L. intracellularis. Natural outbreaks of acute disease, therefore, may partly reflect changes in the use of antibiotics.

a consequence there will be marked variations in sizes of pigs Slaughter weight variations will be noted (and costly!) Acute ileitis: Pigs appear very pale and passes black bloody faeces Bloody watery in-contact pigs scour in several

Summary of ileitis symptoms

Weaners & Growers Clinical signs of chronic and subclinical ileitis are different from acute haemorrhagic ileitis. Chronic and subclinical ileitis Pigs appear clinically alert and active Initially eats well Chronic watery, sloppy diarrhoea. Grey green colour with no mucus or blood evident looks like sloppy cement or cow faeces Gradual wasting and loss of condition In some cases the pigs have a pot bellied appearance Pigs with the chronic and subclinical form can recover over a period of four to six weeks; however there can be considerable losses in feed efficiency and reduced daily gain of up to 0.3 and 80g/day respectively. As

Anaemia and sudden deaths Sows, gilts and boars Pigs appear very pale and passes black bloody faeces Bloody watery in-contact pigs scour in several

Acute Haemorrhagic Ileitis

The acute haemorrhagic form of ileitis sometimes known as PHE, is a much more dramatic and severe form, with black soft faeces, pallor and sudden death. Cases are usually seen in older nave pigs exposed to a relatively high oral challenge dose of bacteria. such as the finishing or fattening period or in young adult pigs in breeding groups. Affected pigs are usually 3 to 12 months old. It is common to see a number of cases together, usually soon after some specific event in the group of pigs, such as moving them to a new building, moving them to a new pen, introduction of new

Anaemia and sudden deaths Abortion may occur in pregnant females

Causes / Contributing factors

The use of continually populated pens Lack of all-in, all-out production Naive animals occur due to antibiotic usage

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 Carry over of infection between batches appears to be a main means of spread Age-related susceptibility to acute ileitis only fattener or older pigs Diagnosis This is based on the clinical picture, postmortem examinations, histology of the gut wall and demonstrating the organism in faeces by a PCR test. A serological test is also available.

during the monitoring period of 2 to 3 weeks post-medication. The use of in-feed premix formulations is also a realistic option for managing both acute and chronic clinical ileitis. Several controlled scientific studies have confirmed the beneficial effects of tiamulin or tylosin premix formulations for control and prevention of ileitis on many farms across Asia. These drugs can be used with confidence for the treatment and control of ileitis. The correct dose for each drug for each method of delivery must be carefully checked before it is used. It is important to realise that drugs given as a parts per million dosage in water or in feed will have different levels in the body of each pig treated because the body weight of each pig will vary with growth. For instance, tiamulin is best used at a rate of 3 to 5mg/kg bodyweight. This usually corresponds to 100 ppm in feed in the grower phase. When pigs are bigger, a higher dose in the feed would be needed to get this correct dosage. Other important issues to consider when evaluating antibiotic treatments include factors such as product quality, cost, the technical and value-added support provided by the product company

involved, withdrawal times and other regulatory issues. These factors can vary among different countries. The several antibiotics found not to be fully effective for an ileitis challenge include bacitracin, virginiamycin and salinomycin. The penicillins and fluoroquinolones likewise have proven ineffective in preliminary trials. An effective vaccine for ileitis has recently been licensed in America and Europe and is now available in parts of Asia and Australia. The vaccine is a live oral attenuated vaccine of Lawsonia intracellularis, known as Enterisol Ileitis, marketed by Boehringer Ingelheim. When added to feed, additives such as heavy metals (copper, zinc), probiotics, acids or enzymes, have not been shown to have any effect on ileitis. Although some inhibitory effect on microbial agents is likely at high levels of inclusion, these levels tend to reduce feed palatability for sensitive pigs. The removal of many in-feed antibiotics previously used at digestion enhancer levels in European pigs in the last 10 to 20 years has corresponded with a rise in the use of these feed additives, but has also coincided with a rise in the proportion of European farms positive for ileitis.

Treatment strategies for ileitis

In actual outbreaks of ileitis, it is possible to use antibiotic agents that target the organism with a specific antibacterial effect. In acute ileitis with high morbidity (many cases in the group) and high mortality, the use of injectable formulations of tiamulin or tylosin is usually recommended for the most at-risk pigs. This is usually followed with water-soluble formulations of tiamulin, lincomycin or tylosin to deliver a high dosage in an effective manner in the water supply of affected pigs. In one controlled clinical study, water medication with 60 ppm of soluble Denagard for 5 days to groups of pigs challenged with ileitis resulted in a good clinical response and reduction of lesions

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