Salmonellosis and Salmonella Infections

Introduction

Salmonella enterica is the genus and species of bacteria that is important to swine producers for two major reasons: 1. Salmonella infections can cause severe disease in pigs (salmonellosis); and 2. Pigs can carry and shed Salmonella indefinitely, which can be a source of Salmonella-associated food poisoning to humans via contamination of pork products.

 

Nearly all swineherds are infected with one or more of the nearly 2,500 serotypes of Salmonella, but only a few serotypes are a primary cause of disease in pigs. Pigs often are sequentially and transiently infected with various serotypes, all of which have potential to cause food poisoning in humans. When disease occurs in pigs (salmonellosis), the usual culprits are either Salmonella Typhimurium (or its variant 4,[5],12:i-), S. Heidelberg, or host-adapted S. Choleraesuis. Diarrhea with stunting, which can occur any time after weaning are the most common clinical signs, but septicemia and pneumonia can also occur. Salmonellosis often occurs with coinfection of other disease agents or risk factors that include environmental or nutritional stresses, commingling of different groups or ages of pigs, poor sanitation or inadequate biosecurity. Although Salmonella colonization of pigs is difficult to prevent, disease is preventable with good management practices, hygiene, and optimizing pig health and vigor.

 

Objectives

• Review relevant biology and ecology of Salmonella
• Describe clinical signs of salmonellosis
• Provide steps to confirm diagnosis of salmonellosis and identify risk factors
• Discuss treatment and control of outbreaks
• Provide prevention strategies that rely on management, biosecurity and immunity
• Increase awareness of public health considerations to motivate improved management practices for pork product safety and overall swine health

 

Salmonellosis: The disease that can result from Salmonella infections

The organism and ecology:

Salmonella commonly infects vertebrates (mammals, avian, reptiles), residing in the intestinal tract for unknown periods of time, and are shed in feces as a source of infection for other animals. The broad host range, long-term fecal shedding, unavoidable fecal contamination of feedstuffs and environments, ability to persistence in the environment, and broad variation of serotypes guarantees that all pigs will be exposed and infected with Salmonella. Even if no disease results, infected pigs may carry and shed one or more serotypes in feces for unknown periods of time.

 

Infection and carriage of Salmonella by pigs is much more common than actual disease caused by this organism. Actual disease (salmonellosis) is caused by only a few of the many serotypes of Salmonella that can infect pigs. The naming conventions for Salmonella can be confusing. Within the genus-species Salmonella enterica, there are >2500 “serotypes” classified by their antigenic formula. This is done by reference laboratories such as National Veterinary Services Laboratory (NVSL) or Center for Disease Control (CDC) and requires weeks for results to become available. The variety of serotypes that have been identified cluster into “serogroups” (i.e. Group A, Group B, Group C, etc.), which often can be determined by local diagnostic laboratories. Many, but not all of the serotypes that are pathogenic (disease causing) to swine, as well as many nonpathogenic serotypes, fall within serogroup B. A few swine pathogens, along with many nonpathogenic serotypes, fall in other serogroups. It should be noted that all Salmonella serotypes are considered potentially pathogenic for humans (Table 1).

 

Table 1: Serotype, serogroup and frequency of isolation of Salmonella from diseased swine and humans.

 

All serotypes of Salmonella are hardy in the environment, persisting in feces and organic material for weeks-to-months. Salmonella are sensitive to most disinfectants, but only after all organic debris and feces are removed from surfaces with thorough washing.

 

Many factors can influence pigs’ likelihood of Salmonella infection, as well as the duration and magnitude of fecal shedding. Pigs appear to be most susceptible to infection with Salmonella immediately post-weaning. Changes in diet and gut function, coupled with the loss of milk provided immunity, commingling, and stresses of transport and vaccination influence infection likelihood. Individual pigs are exposed to infective doses of Salmonella from their mothers, contaminated farrowing areas, load-outs, transport vehicles, or contaminated nursery environments as well as contaminated feedstuffs. The higher the dose of Salmonella ingested, the more likely infection and/or disease will occur. Piglets that are healthy looking, but infected or are exposed at weaning can replicate the bacteria and shed Salmonella in high numbers under stressful conditions, thus magnifying the dose to pen mates. The constant presence of additional potential pathogens can also decrease piglet hardiness and resistance to getting Salmonella infections. Such pathogens include rotaviruses, coronaviruses, E. coli, ileitis (Lawsonia), swine dysentery (Brachyspira) and PRRSV. The constant threat of salmonellosis is a major reason why the management and nutrition of newly weaned pigs is critical. However, Salmonella infections are a threat to pigs at any age, ready to take advantage of similar risk factors and management deficiencies.

 

The serotypes most commonly implicated as primary pathogens that are capable of causing disease in previously healthy pigs, are S. Choleraesuis, S. Typhimurium with its variant 4,[5],12:i:-, and S. Heidelberg (Griffith et al, 2019). Many other Salmonella serotypes may contribute to enteric disease, but usually require predisposing risk factors. All Salmonella can be carried and shed indefinitely, but the less pathogenic serotypes are often transient.

 

Salmonellosis is manifested as clinical disease in two major ways: 1. Septicemia and pneumonia, most often associated with S. Choleraesuis, and 2. Diarrhea and enteric disease, usually caused by serotypes such as S. Typhimurium and its variant 4,[5],12:i:-, S. Heidelberg and a few others. The clinical disease syndromes will be discussed separately, realizing there is considerable overlap in clinical signs and disease expression.

 

Systemic disease: Salmonella Choleraesuis (swine paratyphoid)

Originally thought to be the cause of hog cholera when first isolated in 1885, host-adapted S. Choleraesuis has been commonly obtained from cases of swine pneumonia, septicemia (bloodstream infection) and diarrhea with high death rates since. For the next 110 years, even after eradication of hog cholera, it remained the most prevalent Salmonella serotype (>90% of cases) obtained from diseased swine. In 1991, S. Choleraesuis was estimated to cost pork producers in the United States more than $100 million annually due to death losses, medication costs and poor production efficiency of survivors. Since the use of improved hygiene, improved facilities, age segregation, and introduction of useful vaccines in the mid-1990s, the number of S. Choleraesuis cases resulting in  clinical disease has declined to <10% of the total cases of salmonellosis currently (Table 1).

 

1. S. Choleraesuis is somewhat unique in its ability to survive within cells, some of which (macrophages) distribute the organisms throughout the body. This serotype causes disease mostly in pigs, is rarely isolated from other animals or sources and is considered “host-adapted” to swine. Sows may appear healthy, but serve as carriers of the organism and may irregularly pass this serotype to their offspring via milk and feces. Disease can be seen at any age, but is more common in nursery and grower phases of production in periods of high stress or commingling. When naïve pigs are infected or apparently healthy disease carriers are stressed, pigs can develop septicemia. Once organisms are in the blood, they can then localized to lungs, liver, brain, joints or gut and cause inflammation of those organs. Affected pigs become dull, have fevers, and can often develop blue-purple skin on their ears and body (Figure 1). Pigs usually have respiratory distress with “thumping” because of lung inflammation. Gut inflammation allows intestinal bacteria to reach the bloodstream resulting in systemic infection. Diarrhea becomes prominent as the disease progress, with death being uncommon.

 

 

Since clinical signs are not specific, a swine veterinarian often must perform a necropsy and collect samples for laboratory testing. Diagnosis is by isolating Salmonella by bacterial culture of affected tissues such as the lung, liver, spleen or intestine. To confirm that S. Choleraesuis is the cause, additional testing and serotyping are performed for a definitive diagnosis. It is also wise to confirm microscopic lesions of salmonellosis in these tissues, which will also rule out the presence of other co-infections. Coinfections with multiple potential pathogens, including bacteria, viruses, and parasites are common, as are stressful insults. Your swine veterinarian and laboratory diagnostician can determine which tests to perform based on clinical signs, tissue abnormalities seen with the naked eye and those identified under the microscope. Other serotypes of Salmonella occasionally can cause septicemia, usually when animals are first weakened by other disease agents.

 

Treatment of affected individual pigs with injectable antibiotics is often necessary since sick pigs do not eat or drink enough to receive sufficient medication by feed or water routes. Effective modified-live vaccines became available in the 1990s and are very useful tool for disease prevention. Vaccines, coupled with age segregation, improved housing and better nutrition are likely why this particular serotype has become a less common disease cause in the last few decades.

 

Enteric disease: Salmonella Typhimurium and variant 4,[5],12:i:-, S. Heidelberg, others

Although many different serotypes can be isolated from diseased pigs, only a few serotypes of Salmonella are considered primary causes of disease. The most important of these are S. Typhimurium and its variant 4,[5],12:i:- (Naberhaus et al, 2020). These serotypes cause disease by entering the cells lining the intestine and colon, spreading locally (occasionally through the blood), resulting in fever and diarrhea. Affected pigs often have greenish-yellow, watery diarrhea, are lethargic, off feed, gaunt and dehydrated (Figure 2). In severely affected pigs, the disease tends to persist with recurring bouts until the animal is stunted, emaciated and eventually dies. Infected pigs can shed virulent Salmonella for months in their feces, and when clinically affected shed high amounts.

 

 

Salmonella Typhimurium and its variant 4,[5],12:i:-, as well as S. Heidelberg have all been demonstrated to cause diarrhea when healthy pigs are experimentally infected (Griffith et al, 2019). S. Heidelberg typically causes a watery diarrhea similar to E. coli. The detection of S. Typhimurium variant 4,[5],12:i:- has been rapidly increasing in recent years from humans, swine, bovine and poultry, a trend that is being monitored with concern (Yuan et al, 2018).

 

Pigs that are debilitated, stressed or pigs exposed to high doses of Salmonella may develop salmonellosis from a variety of serotypes. Other serotypes can be isolated from sick pigs, but are usually due to additional risk factors or in animals weakened by previous infectious, metabolic, environmental or nutritional causes. The role of Salmonella in these cases may not be the cause of disease, but is likely contributing to overall disease severity. For all serotypes of Salmonella, the higher the dose ingested, the more likely infection and disease will result, emphasizing the benefit of sanitation and separation of sick, shedding pigs.

 

Salmonellosis can occur in pigs of any age. The period of greatest detection and disease is from pigs 3-6 weeks of age, with gradual decline throughout grower and finisher phases (Schwartz, 2012). The high detection rates in the post-weaning period are not surprising considering the numerous insults and stresses pigs face at this age. The stresses of weaning, transport, starting on feed, gut microbe populations shifts, environmental stresses, commingling and other disease challenges are unavoidable at this age. Salmonella disease outbreaks can also occur with abrupt feed changes or viral infections (e.g. coronaviruses) as pigs get older.

 

Diagnosis

The clinical signs caused by Salmonella, often a “rolling” diarrhea with feces of various colors and consistencies, are not enough for diagnosis. For accurate diagnosis, a swine veterinarian will assess history, clinically examine pigs, and often perform tissue examinations by necropsy of dead or affected pigs. Lesions that can sometimes be seen with the naked eye with gut salmonellosis include; fluid, foul-smelling feces in the colon; reddening and swelling of the gut wall; ‘strings’ (fibrin), additional fluid and/or focal ulcers on the lining of the colon and/or small intestine; and swollen gut lymph nodes. As mentioned previously, the lesions associated with systemic S. Choleraesuis may include lung inflammation and swelling, enlarged lymph nodes and jaundice (yellow tint) as well. While lesions can be presumptive for salmonellosis, none of these lesions are specific for salmonellosis and co-infections with other infectious diseases are common. Often, submission of tissues and feces to a diagnostic laboratory is warranted to confirm salmonellosis and rule out the presence of other diseases.

 

The detection of Salmonella in samples is most often by bacterial culture or molecular testing (PCR). Bacterial culture of tissue or feces is usually preferred so that antibiotic sensitivity can be determined and the organism can be serotyped. Samples should be from affected pigs that have not recently received antibiotics via feed, water or injection. It is expected that Salmonella will be easily isolated in high numbers from tissues of affected pigs. Often, microscopic examination of the colon, intestine, lymph nodes, liver and lung is needed to confirm that the tissue abnormalities are from salmonellosis. Microscopic examination is also useful to determine other diseases present or if additional testing should be considered. Common coinfections with gut Salmonella can include rotaviruses, coronaviruses, ileitis (Lawsonia), parasites and swine dysentery (Brachyspira), therefore it is important to rule those out before implementing expensive interventions specific for salmonellosis. It is not uncommon that other disease processes/organisms may be present as risk factors for Salmonella disease expression.

Even though Salmonella can often be isolated from pig feces or tissues, the detection of Salmonella is NOT the same as a disease diagnosis of salmonellosis. Salmonella can often be detected in feces of healthy pigs as well as from feces of pigs sick with other diseases. The detection of Salmonella requires additional information for interpretation, including clinical signs and characteristic tissue and/or microscopic lesions before assigning a diagnosis of salmonellosis.

 

The serogroup (A, B, C, etc.) of a Salmonella isolate can usually be determined from cultures fairly quickly, but serotyping is performed by reference laboratories, hence serotyping results are often delayed for several weeks. Serogroup B contains S. Typhimurium and S. Heidelberg while serogroup C1 contains S. Choleraesuis (Table 1). However, all serogroups also contain less lethal Salmonella, hence greater confidence in diagnosis is achieved with serotyping, especially before making major, expensive, long-term intervention decisions. Serotyping is also used to implicate or rule out sources of infection.

 

Oral fluids can be tested for Salmonella (Johnson et al, 2011), however, oral fluids are largely the same as “environmental samples” and expected to be positive for Salmonella, hence have no value as a useful sample for diagnosis of salmonellosis. Similarly, detection of antibody with serologic (blood) tests are not used for diagnosis of disease. These two test types are sometimes used to determine if and/or when exposure is taking place, but they do not confirm disease diagnosis. Diagnosis of disease is by aligning clinical signs, tissue and microscopic lesions and the detection of Salmonella while assessing for co-factors. Diagnostic pathologists tend to look for “alignment” of available information and offer information that is valuable to the submitting veterinarian to make the final herd diagnosis of salmonellosis.

 

Steps in diagnosis of salmonellosis

1. Swine veterinarians can provide a thorough and objective assessment of clinical signs, history, and risk factors to implicate a possible role for Salmonella in disease
2. Swine veterinarians usually will examine tissues from dead or typically affected pigs for lesions that might suggest a role for Salmonella and/or other enteric pathogens
3. Samples are collected based on clinical signs, tissue lesions and the agents that could be contributing to disease, which are then submitted to a diagnostic laboratory
4. At the laboratory, appropriate tests are performed, interpreted and reported given the information provided in numbers 1-3 to eliminate or confirm potential causes. These tests often include:
   1. Microscopic examination (histopathology) to confirm tissue changes compatible with salmonellosis, and to eliminate or implicate other causes of disease
   2. Bacterial culture to confirm presence of Salmonella, grow a colony to determine serotype, and to test antibiotic sensitivity of that colony
   3. Other tests for other agents or risk factors as directed by herd history, clinical signs, lesions and laboratory results
5. Timely reporting of laboratory results will list findings based on provided history, laboratory testing and tissue assessments, usually ending with a laboratory diagnosis and comments
6. The swine veterinarian will then use this information to make the final “herd diagnosis” and recommend intervention strategies and treatment options

 

Treatment and control

A diagnosis of salmonellosis usually leads to some level of immediate treatment or intervention in the groups in which it occurs. Immediate treatment is usually in the form of antimicrobial intervention. The selection of an appropriate antibiotic, dose and route of administration is based on antibiotic sensitivity testing of cultured colonies, along with specific circumstances and/or historical experiences. Specific treatments, supportive therapy and management should be based on discussion with a swine veterinarian. Sick pigs shed high numbers of Salmonella so segregating sick pigs to a separate pen can help prevent disease spread. Relying only on antibiotics for long-term control will ultimately fail due to resistance and/or build-up of overlooked risk factors. Long-term prevention and control strategies should be based on all available information, including risk factors (e.g. diet, environment, management), other gut diseases present (e.g. hemolytic E. coli, coronaviruses, rotaviruses, Lawsonia, Brachyspira) or diseases affecting other organs (e.g. PRRSV, IAV-S, PCV2).

 

Prevention

There are two major approaches to preventing Salmonella outbreaks; both require proper and consistent execution of processes and procedures on farm. The first is maximizing pigs’ resistance through proper management, environmental control and disease management. The second is minimizing exposure dose and/or introduction of new serotypes through proper sanitation and hygiene of facilities and feed, and by avoiding the commingling of different populations. Thorough management and husbandry practices coupled with proper nutrition and facility management for each stage of production will help guarantee vigorous healthy pigs, which improves resistance to potentially harmful and common agents. When coupled with excellent sanitation, ongoing hygiene, and sound execution of basic biosecurity principles, the result will be decreased impact of Salmonella, E. coli, rotaviruses, coronaviruses and other organisms. Water quality (pH, coliforms, etc.) and availability is always important; testing of water is warranted if salmonellosis is a recurrent problem.

 

Modified-live vaccines are quite efficacious for S. Cholerasuis and also have demonstrated efficacy for S. Typhimurium. Strategic use of these vaccines in farrowing, at weaning, in the nursery-grower phases, in gilts pre-breeding, or in sows have all been valuable. In certain settings, annual or bi-annual sow farm booster vaccinations may also be required. Consultation with a swine veterinarian is very important in product selection, timing of application and the specific dosing of these products. They must be applied properly in the absence of antibiotics, to ensure viability of live vaccines. Killed vaccines may offer some production benefits, but are generally of limited value for long term disease prevention in swine.

 

Biosecurity considerations:

Biosecurity protocols have two important objectives. The first is to keep new agents or new “strains or types” of infectious agents from entering the population at a particular farm site (external biosecurity). The second is to minimize the dose, transmission and exposure of groups of pigs to the agents already on the farm (internal biosecurity). Both are important concepts for prevention of Salmonella outbreaks on farms. All biosecurity protocols should be developed and implemented with a swine veterinarian.

 

The key components of external biosecurity are similar for most infectious agents that are not already present on the farm.

1. Disease history of new sources of pigs should be investigated prior to placement to prevent facility contamination with “new” serotypes of Salmonella. Breeding stock should be quarantined per protocols for other agents of high risk. Any illnesses or clinical signs should be investigated with aid of a swine veterinarian
2. Isolate your production facility from visitors, assure all vehicles hauling pigs are cleaned, disinfected and dried prior to use, including vehicles transporting pigs to market
3. Bird-proof facilities to keep out birds, wildlife and other animals to reduce farm-to-farm exposure to Salmonella
4. All footwear and clothing exposed to off-site swine or manure should be changed before entry. Decontaminate all fomites such as boots, clothing and pig handling equipment
5. Biosecurity protocols should be implemented for all personnel in potential contact with pigs or pigs’ environment, including service personnel
6. Aggressively suppress rodents and insects in the facilities to reduce exposure
7. Clean and disinfect load-out area immediately after use

 

Internal biosecurity aims to minimize the dose and opportunity for Salmonella spread within the farm and follows similar concepts as external biosecurity, but at the level of different ages/stages or facilities that are present on a site. Emphasis is placed on:

1. Age segregation with all-in / all-out production. Do not hold pigs back or commingle age groups or sources in any way
2. Aggressively clean and sanitize facilities and loading areas between groups
3. Change or wash boots, utensils and equipment between different rooms, buildings, age groups or pig sources on the farm. Any source of fecal matter can spread the Salmonella infection

 

Salmonella in pork products and human food poisoning

Over 1.3 million cases of salmonellosis occur in humans in the U.S. each year. The sources of infections to humans are many, with food being a major source. Animal products (beef, poultry, pork) as well as vegetables, fruits, nuts and spices are the most common sources of Salmonella in the human food chain. While pork is not commonly implicated as a source to humans, Salmonella contamination of pork products has been a major concern for food safety. Contamination of pork products generally occurs at slaughterhouses or packing plants from fecal contamination during meat processing. Most slaughterhouses and packers take necessary steps to control Salmonella contamination. Some transmission of Salmonella between pigs can occur quite quickly in staging and resting areas of market swine. However, the ultimate source of Salmonella are healthy looking, carrier market swine that shed Salmonella, sometimes with increased numbers as the result of transportation stress. On-farm Salmonella reduction programs are common in some regions of the world, and are a general goal of the food industry at large. Most of the Salmonella reduction programs focus on sound management practices that have broad application to other health challenges as well. The producers’ role is to be aware that pork may be a source of human infection, and to implement biosecurity and management practices that reduce the likelihood of Salmonella infection in market animals. The steps to control salmonellosis on farm are generally useful for decreasing Salmonella infection in market hogs.

 

Summary

Salmonella infections are very common in swine, can cause disease in pigs and can be a source of human infection through contaminated pork products. Salmonella bacteria are diverse, with over 2,500 serotypes, but only a few are associated with disease in pigs. The disease that results from Salmonella infection, salmonellosis, can occur at any age, generally through diarrhea and dehydration, or as septicemia and lung inflammation, either of which may be severe and fatal. Proper diagnosis, treatment and prevention of salmonellosis relies heavily on expertise from swine veterinarians.

 

Treatment of acute disease may rely on antimicrobials, but prevention of salmonellosis is preferred. Prevention is best achieved by; 1. Maximizing resistance to infection through proper nutrition, management and prevention of other diseases, and 2. Minimizing the exposed dose through continuous sanitation of facilities, transport vehicles and feedstuffs, along with avoiding commingling of different populations. Modified live vaccines are useful in overall strategies for prevention and control. Common biosecurity principals that are broadly applicable to many diseases are also useful for preventing Salmonella outbreaks.

 

As a zoonotic agent that can cause disease in humans, the public health considerations are also a major motivation for improved management practices for pork product safety and overall swine health.

 

References and Citations

Griffith, R.W., Carlson, S.A and Krull, A.C. 2019. Salmonellosis. In: J. J. Zimmerman, L. A.

 

Karriker, A. Ramirez, K.J. Schwartz, G. W.  Stevenson and J. Zhang, editors, Diseases of Swine. Wiley-Blackwell, Hoboken, NJ. p. 912-925.

 

Johnson, JJ; Johnson, J; Olsen, C; Schwartz, K; Zimmerman, J; and Engle, M. 2011. Feasibility of oral fluids for detection of antibody response to porcine parvovirus, Leptospira, Swine influenza, Lawsonia, or Salmonella in adult swine.  Annual Meeting of the American Association of Swine Veterinarians, Phoenix, AZ.

 

Naberhaus S, Krull A, Arruda B L, Arruda P, Sahin O, Schwartz KJ, Kreuder. 2020. Pathogenicity and competitive fitness of Salmonella enterica serovar 4,[5],12:I:- compared to Salmonella Typhimurium and Salmonella Derby in swine. Frontiers in Veterinary Science, 6:502.

 

Schwartz, K.J. 2012. Salmonella Diagnostics and Interpretation: What Does It All Mean?, Proc of Swine Disease Conference, Ames, Iowa 2012 p55-68, https://www.aasv.org/library/swineinfo/Content/ISU/2012/055_Schwartz.pdf.

 

Yuan C, Krull A, Wang C, Erdman M, Fedorka-Cray PJ, Logue CM, and O’Connor AM. 2018. Changes in the prevalence of Salmonella serovars associated swine production and correlations of avian, bovine and swine‐associated serovars with human‐associated serovars in the United States (1997–2015). Zoonoses Public Health, 65:648–661.