Intracellular Lawsonia

Proliferative enteropathy (PE), caused by Lawsonia intracellularis, is considered one of the most significant intestinal diseases affecting swine production worldwide. When co-infected with Brachyspira hyodysenteriae, the symptoms of diarrhea are exacerbated. This disease has a substantial impact on pig farming, leading to diarrhea in animals, poor feed conversion rates, and reduced growth performance—resulting in affected pigs experiencing a daily weight gain that can be as low as 0.012 kg ± 0.01 kg. Therefore, enhancing our understanding of the factors influencing the spread and development of this disease within pig populations is crucial for effectively reducing the incidence of porcine enteritis.

In laboratory animals, Intracellular Lawsonia can infect experimental pigs, monkeys, hamsters, ferrets, rats, rabbits, and more. Currently, the national standard does not list Intracellular Lawsonia as a pathogen required for exclusion testing. However, in practical production, farming, or experimental settings—especially among animals exhibiting diarrhea symptoms—the bacterium remains a potential infection source and should be considered one of the pathogens to account for during diarrhea diagnosis.

Intracellular Lawsonia is a Gram-negative bacterium whose cells can appear helical, curved, or spindle-shaped, and some strains even possess flagella. It stains positively with the acid-fast method and is typically found within the cytoplasm of intestinal cells. Remarkably, it has yet to be successfully cultured on artificial media, though it can grow in certain intestinal cell cultures. Intracellular Lawsonia can survive in feces for up to two weeks at temperatures ranging from -15°C to 15°C. Moreover, pigs infected with this bacterium excrete high levels of the organism in their feces, yet the infectious dose required is remarkably low. First reported in 1973, it was previously known by various names, including "Campylobacter-like bacterium," "ileal symbiotic intracellular bacterium," "intracellular bacterium associated with proliferative enteritis," "Helicobacter-like microorganism," "intracellular bacterium linked to porcine proliferative enteropathy," and "Campylobacter-like intracellular bacterium associated with porcine proliferative enteritis." In 1995, it was officially named "Intracellular Lawsonia."

Differences in prevalence may stem from variations in housing, management practices, and feeding methods, which could influence the extent of transmission both between and within livestock herds. Moreover, in many countries, the use of antimicrobial feed additives might mask these underlying infection patterns. Intracellular Lawsonia bacteria in the environment can persist on contaminated surfaces such as residual feces, boots, and insects, enabling long-term environmental persistence and facilitating oral-fecal transmission to pigs. As a result, ileitis can spread rapidly within pig populations and is notoriously difficult to eradicate. Cases have been reported in numerous countries, including the UK, the U.S., South Korea, Australia, Mexico, Canada, and China. For instance, in 1998, Thomson et al. documented that 15% of cattle herds exhibited intestinal lesions caused by Lawsonia infection; and in 2005, studies revealed that 46% of diarrheic pig herds were infected with Lawsonia. In contrast, experimental animals, whose husbandry practices differ significantly from those used for commercial livestock, typically show lower infection rates. According to our company’s testing data from 2022–2023, the prevalence of intracellular Lawsonia bacteria in laboratory pigs was 5.5%.

Depending on the production model and antibiotic usage patterns, the serological conversion patterns of Lawsonia intracellularis vary. In single-site pig farms, infection with Lawsonia intracellularis typically occurs several weeks after weaning, as maternal antibodies gradually wane. The infection then spreads via the oral-fecal route among nursery pigs, growing-finishing pigs, and gilts—this represents the classic infection pattern. However, if antibiotics are administered at different stages within the herd, intermittent infections may emerge in nursery, growing-finishing, and adult pigs—a non-typical infection pattern. Porcine ileitis is widespread across pig farms in various regions of China; current surveys have primarily focused on areas such as East China, South China, and Central China. In recent years, pig farming has also been expanding rapidly in Northeastern and Southwestern China. Yet, to date, there have been no reported outbreaks of porcine ileitis in these emerging pig-producing regions. Moreover, the infection rates of ileitis differ across distinct stages of pig production, with regional variations in peak infection periods. Generally, incidence and positivity rates remain low just before nursery pigs are moved out, but then surge rapidly afterward. By contrast, growing-finishing pigs, gilts, and multiparous sows exhibit significantly higher positivity rates. Importantly, ongoing transmission cycles persist within individual pig farms, contributing to the continued spread of the disease.

Based on the clinical symptoms, the disease can be classified into acute, chronic, and subclinical forms. This bacterium primarily causes proliferative enteropathy, intestinal adenomatosis, and proliferative enteritis in pigs, leading to inflammation of the intestines—especially the ileum—characterized by thickening of the ileal wall and edema of the intestinal mucosa, resulting in brain-like wrinkles. In acute cases, hemorrhagic enteritis may occur, often accompanied by mortality. The most common lesion sites are located in the distal 60 cm of the small intestine and within the upper third of the colon adjacent to it. Affected pigs exhibit thickened intestinal walls and increased luminal diameters. Upon careful examination of the terminal ileum, particularly within 10 cm near the ileocecal valve—this area is considered the primary site of infection—lesions become evident. In chronic cases, pigs typically show signs of emaciation, stunted growth, reduced feed intake, and persistent diarrhea, producing loose, thin, gray-green feces that may even progress to watery stools. A hallmark feature of these cases is the overall poor uniformity observed across the pig herd. Post-mortem examinations reveal that the intestinal mucosa has thickened dramatically, resembling a tubular structure with deep, brain-like folds. Notably, the mortality rate for chronic ileitis is relatively low (1–5%), often linked to secondary infections. Remarkably, affected pigs usually begin to recover between 4 and 10 weeks after the onset of clinical symptoms. Compared to healthy pigs, infected animals experience an average daily weight gain reduction of 6–20%, while their feed conversion ratio increases by 6–25%. The subclinical form of ileitis typically manifests only as slow growth and uneven development among pigs. Its occurrence mirrors that of the chronic type, potentially affecting pigs at any stage of growth—from 2 to 20 weeks of age.

After infection, pigs in the growing stage can exhibit clinical symptoms ranging from mild, common signs and diarrhea with low mortality rates to acute, severe disease characterized by hemorrhagic or mucoid-hemorrhagic diarrhea, leading to critical conditions and high mortality. Hemorrhagic diarrhea occurs across all stages of post-weaning and growing-finishing pigs, accompanied by clinical signs such as intermittent diarrhea, reduced appetite, and stunted growth.

Pigs infected with Lawsonia bacteria show significant impacts on intestinal function. Scholars have investigated the relationship between porcine ileitis and the number of cells involved in mucosal immunity, as well as digestive enzyme activity. The findings reveal that pigs suffering from ileitis exhibit symptoms such as weight loss, reduced appetite, decreased body weight, and lower feed conversion rates. In the infected group, there was a notable decline in lymphocytes and mast cells in the pigs, leading to impaired protective functions of the small intestinal mucosal barrier. Additionally, digestive enzyme activity in the gut was diminished, particularly with significantly reduced trypsin activity in the jejunum and ileum, which in turn inhibits the efficient digestion of nutrients like proteins in the small intestine. Furthermore, reduced alkaline phosphatase activity was observed, further impairing the intestine's ability to absorb essential nutrients.

The most common and sensitive method for detecting Lawsonia intracellularis is PCR testing of fecal samples. Serological methods are also an option, though they tend to have lower specificity. This disease has a relatively long incubation period—bacteria are not shed in the feces until about two weeks post-infection—so early-stage infections may yield false-negative results. To improve detection rates, intermittent sampling can be employed. When performing fecal PCR tests, it’s advisable to simultaneously conduct IFA serological assays. Clinically, it’s important to differentiate this condition from swine dysentery. Notably, in pig populations exhibiting only subclinical symptoms, fecal PCR results may occasionally be suppressed. Alternatively, intestinal tissue sections can be stained and examined microscopically, revealing intracellular bacteria within the cytoplasm of intestinal cells—specifically, Gram-negative, curved bacilli that test positive with acid-fast staining.

Intracellular Lawsonia bacteria are sensitive to quaternary ammonium disinfectants but exhibit some resistance to phenol- and iodine-based sanitizers. Implementing a "all-in, all-out" production system combined with rigorous empty-housing disinfection protocols can effectively reduce the incidence of ileitis. Meanwhile, regular rodent and insect control measures should be carried out to minimize the risk of disease transmission via humans, rodents, and insects. When introducing replacement pigs, it is crucial to first isolate and acclimate them properly—only after confirming they are free from ileitis infection or have already completed appropriate health-care treatments should they be integrated into the existing herd.

The ileitis vaccine comes in various forms, such as oral and injectable options. However, usage results in the United States have shown that the vaccine’s effectiveness is generally moderate—vaccination can only control about 70% to 80% of clinical cases of ileitis, but fails to manage subclinical cases. When it comes to controlling ileitis, antibiotics prove more effective than vaccination. Additionally, adding heavy metals (such as zinc and copper), probiotics, organic acids, or enzymes to feed has not demonstrated any reliable benefits against proliferative enteritis. In a comparison of commonly used antibiotics in pig farms against *Lawsonia intracellularis*, the results revealed that macrolides and tiamulin are the most sensitive, followed by tetracyclines, while chloramphenicol and penicillin-based drugs show little to no efficacy against the pathogen.

References

1. M. Jacobson, M. Gerth, N. Holmgren. The Prevalences of *Brachyspira* spp. and *Lawsonia intracellularis* in Swedish Piglet-Producing Herds and Wild Boar Populations [J]. Vet. Med. B 52, 386–391 (2005).

2. Dong Bingmei, Donna, Wang Jinliang, et al. Establishment and Application of an Intracellular Lawsonia PCR Detection Method[J]. Chinese Journal of Preventive Veterinary Medicine, 2011, 33(5):370-373.

3. Liu Yan, Xue Qinghong. Advances in Research on Porcine Proliferative Enteritis [J]. Chinese Journal of Veterinary Medicine, 2006, 40(9):41-44.

4. Ren Jinglei. Epidemiological Investigation and Progress in Prevention and Control of Porcine Ileitis [J]. Pig Science, 2020, 37(8):52-56.

5. H. Nathues, K. Holthaus, E. Grosse Beilage. Quantification of Lawsonia intracellularis in porcine feces by real-time PCR [J]. Applied Microbiology 107, 2009–2016 (2009).