Porcine salmonellosis

M-L PENRITH, J A NESER AND M M HENTON

GENERAL INTRODUCTION: FACULTATIVELY ANAEROBIC GRAM-NEGATIVE RODS Salmonella spp. infections

Introduction

Infection of pigs with certain serovars of Salmonella results in clinical disease with important consequences for pig production. Pigs can also act as reservoirs for a wide variety of salmonellas with zoonotic potential, leading to their introduction into the human food chain.¹⁴

Porcine salmonellosis usually manifests as septicaemia or enterocolitis in weaned pigs, and can result in serious production losses. Salmonella was first isolated from diseased pigs in 1886 by Salmon and Smith.⁵² The pigs proved to be suffering from classical swine fever (hog cholera), and it was only when that disease was eradicated from the USA that it was recognized that the bacterium isolated, named Salmonella Choleraesuis, was capable of causing septicaemia in pigs.^{14, 52} Enterocolitis caused by S. Typhimurium is also well known in pigs, and at present is the most common form of porcine salmonellosis in pigs in Europe, while S. Choleraesuis remains an important cause of disease in the USA.^{14, 42, 43} Salmonella Choleraesuis was isolated from pigs in outbreaks of suspected African swine fever in South Africa in the first half of the last century,¹² but was subsequently, until 2000, only rarely diagnosed in South Africa. Although on average several thousand isolates from all domestic animal species are received annually by the Onderstepoort Veterinary Institute for typing, numbers from pigs are small (Table 153.1). This suggests that porcine salmonellosis as a disease is uncommon in South Africa, and in recent years until 2000 S. Typhimurium has been the most frequent isolate (Table 153.1). However, in 2000, four isolates of S. Choleraesuis were obtained from three farms. Two were separated by a river, but with road access from different areas, and the third was 50 km distant, with ostensibly no contact with the other two. The source of this pig-associated Salmonella infection is unknown, but its occurrence demonstrates the unpredictability of outbreaks and emphasizes the need for laboratory examination of suspect cases.

Salmonellosis in humans, caused by numerous serovars, the most notable of which is S. Typhimurium, is an important food-borne disease. It usually manifests as a severe gastro-intestinal disturbance that may be fatal in older people and children. Increasing concern about the potential of animal products to cause disease in humans has resulted in the institution of quality control programmes that include routine on-farm and abattoir sampling for pathogenic organisms. Salmonellas are commonly isolated from both healthy and diseased pigs, and, unless associated with characteristic clinical signs and lesions, are unlikely to be significant to the health of the pig. However, outbreaks of human salmonellosis have been traced to pork products.^{10, 14, 38} The problem is compounded by the demonstration of multiple antibiotic resistance among some of the strains commonly isolated.^{2, 14, 22, 38}

Aetiology

For general information on the morphology, physicochemical and other properties of salmonellas, consult the introduction to Salmonella sp. infections.

Most cases of porcine salmonellosis have been associated with S. Choleraesuis or S. Typhimurium. Salmonella Choleraesuis is associated mainly with septicaemia, but pneumonia also occurs as a separate entity.^{26, 43, 46} Meningoencephalitis may occur in a limited number of cases.^{43, 50} Infection with S. Typhimurium usually presents as enterocolitis, and rectal strictures, generally as a complication of colitis, have been reported and experimentally confirmed.^{48, 49} Outbreaks of disease caused by S. Typhisuis have been reported in Europe, Asia and the USA.^{5, 17, 52} Salmonella Typhisuis does not grow well under standard conditions for culture of salmonellas, and it has therefore been suggested that this organism may be underdiagnosed.⁵² Salmonella Dublin and S. Enteritidis have been reported from cases of meningitis in suckling pigs.^{29, 32, 40, 52} Numerous serovars have been isolated from healthy pigs.¹⁴

Table 153.1 Salmonella isolates from diseased pigs typed annually at the Onderstepoort Veterinary Institute, 1994 to 2000

Epidemiology

Salmonellas are ubiquitous organisms that have been isolated from virtually every species of vertebrate from which culture has been attempted.⁵² They are also relatively resistant in the environment, which may consequently remain contaminated for long periods, although they are susceptible to heat, sunlight, and certain disinfectants.⁵²

Porcine salmonellosis usually occurs in pigs maintained in intensive management systems.^{14, 52} Given the wide range of potential hosts for at least S. Typhimurium, there is no reason why pigs kept under extensive conditions should not be affected, and it is likely that in many countries the disease in smaller herds is simply not reported. Salmonella Choleraesuis usually affects pigs from weaning to five months of age, but sometimes adults as well. Suckling piglets rarely develop salmonellosis, possibly due to protection afforded by antibodies obtained in colostrum.¹⁴ They may, however, become infected.^{18, 47} Disease usually does not appear before weaning.⁴³ Enterocolitis caused by S. Typhimurium occurs almost exclusively in weaners, but neonatal piglets orally infected with S. Typhimurium may develop disease similar to that observed in weaners.⁵¹ Once pigs become clinically ill, they shed large numbers of salmonellas. Infection probably occurs most frequently by the direct faecal-oral route, but aerosol and dust-borne infections, and mechanical spread via contaminated equipment, clothing and boots probably play important roles.¹⁴

Salmonella Choleraesuis is adapted to pigs and is not commonly isolated from other sources.^{19, 43} There is evidence that, if the breeding herd is infected, most pigs in the piggery eventually become infected.⁹

Experimental induction of the disease requires the administration of large numbers of the organism.¹ Introduction of S. Choleraesuis into a herd is usually by carrier pigs. Sincemany pigs exposed to infection do not become carriers, it appears that only a small proportion of pigs is responsible for the maintenance of the organism.¹⁹ Salmonella Typhimurium has amuch wider host range, and pigs may become infected due to contact with a wide variety of species, including birds, rodents, cats, dogs, cattle and insects,^{14, 38, 52} although infected pigs are probably the most usual source of infection.

The existence of a carrier state of salmonellas is well documented.^{43, 52, 53} Shedding of the organism by carriers is sporadic and probably induced by stress.^{43, 44} Mixing of pigs of different ages and/or from different sources, transport, crowding, and either immediate slaughter or prolonged holding periods in abattoir lairages are apt to induce massive shedding of salmonellas.^{14, 27, 52} Environmental factors, such as poor ventilation and sanitation, as well as poor nutrition, infection with other diseases and parasites, and managemental practices, e.g. continuous-flow production that permit a build-up of pathogens, predispose to salmonellosis.⁴³

The identification of individual carriers is difficult. Because faecal shedding is sporadic, the bacteriological examination of individual faeces samples is not a reliable indicator of herd infection, and repeated negative sampling may fail to reveal carriers.^{18, 23, 43, 52} To detect infected herds, the examination of pooled samples of faeces has been found to be effective,^{24, 30, 35} and superior to the use of rectal swabs for this purpose.³⁰ Tonsillar swab or buffy coat culture may provide a more reliable method of detecting carriers.⁴³ In one study it was found that the results obtained from serology are variable.

Within groups of pigs, there was evidence that pigs shedding salmonellas had on average higher antibody titres than those of non-shedders,⁷ but absolute values were revealed above which shedding might have been expected. Other studies have suggested that active infection with shedding cannot always be correlated with levels of antibodies against salmonellas,¹⁴ and to regard all serologically positive pigs as potential carriers would result in excessive culling.⁵²

The epidemiology of human salmonellosis caused by salmonella-contaminated pig carcasses and pork products derived from them is complex. Numerous serovars have been isolated from pigs that have shown no evidence of disease. Since outbreaks of human disease have been associated with pork products, it is assumed that the slaughter of pigs infected with salmonellas may constitute a source of infection for humans. Even if pigs are not shedding salmonellas at the time of slaughter, handling of their carcassesmay result in contamination of the meat from the gut or lymph nodes.

The source of infection of pigs by non-specific serovars is largely unknown. Contamination of their feed with salmonellas is a potential source of infection, but there is little evidence that the serovars identified in feed actually infect pigs.^{31, 45, 52} However, it is recommended that efforts should be made to reduce the prevalence and numbers of salmonellas in pig feed, which can act as a source of infection for birds and rodents as well as pigs, and may pose a threat to human health whether or not they infect the pigs.²² Effluent from piggeries has been shown to be contaminated with salmonellas, and although dilution probably reduces the danger of recontamination of pigs, it has been suggested that using recycled waste water may promote infection.²⁵ Contact with faeces is the most important source of infection of pigs,²³ and faeces flushed through open-flush gutter systems are a more likely source of Salmonella infection than the water used.¹⁰

Pathogenesis

Oral infection with salmonellas results in multiplication of the organisms in the intestine and invasion of the intestinal mucosa, followed by multiplication in the gut-associated lymphoid tissue.^{6, 39} Intranasal inoculation of S. Typhimurium in pigs that have been subjected to oesophagotomy has demonstrated that disease may develop in the absence of colonization of the gut.¹⁶ The lungs are also a site of initial multiplication in pigs naturally infected with S. Choleraesuis.¹⁹ Subsequent disease will depend on the number of infecting organisms, the virulence of the serovar, and the efficacy of the host’s immune system to limit penetration and multiplication.⁵² Restriction of the infection to the intestinal tract and associated lymph nodes results in enterocolitis, which initially manifests clinically as a watery diarrhoea due to hypersecretion, and may progress to more serious diarrhoea as a result of mucosal damage.

When the barrier to penetration beyond the intestinal tract fails, as is frequently the case in S. Choleraesuis infections, spread to many organs results. Infection via the aerosol route results in localization in the lungs,^{14, 20, 46} and can also lead to generalized disease or enterocolitis.^{14, 16}

Numerous virulence factors have been identified, but the role of most of these in the pathogenesis of salmonellosis is unknown¹⁴ (see Bovine salmonellosis). Some of the factors that are likely to contribute to porcine salmonellosis are flagella and adhesins (which facilitate contact with and possibly subsequent invasion of enterocytes), cytotoxins, heat-shock proteins, and lipopolysaccharide (endotoxin).^{14, 34}

Septicaemic effects are due to widespread inflammation in many organs, with release of cytokines and other bacterial toxins, including endotoxin, which is responsible for vascular damage and thrombosis that characterize terminal cases of septicaemic salmonellosis.^{4, 14} Damage to pulmonary tissue is believed to be due to the release of bacterial toxins rather than invasion of pneumocytes by bacteria.¹⁴

The role of enterotoxin in S. Typhimurium-induced diarrhoea has not been defined. Salmonella Typhimurium infection, as with choleratoxin, results in the activation of 5-hydroxytryptamine and PGE2. It is uncertain whether the reaction is caused by enterotoxin or by inflammatory mediators,²¹ because the influx of neutrophils into the mucosa appears to be necessary for the increase in fluid that results in diarrhoea, which is not the case with choleratoxin.²¹ Neutrophils appear early in infection and are rapidly superseded by macrophages.⁵²

Rectal strictures as a complication of S. Typhimurium enterocolitis are believed to result from salmonella-induced ischaemic proctitis, as the lesion occurs at the mucocutaneous junction, a region with a relatively poor blood supply.⁴⁹

Clinical signs

Clinical signs are determined by the serovar as well as by the route and severity of infection. Signs of disease may appear as soon as 24 hours, but usually 36 to 48 hours, after infection. On the other hand, pigs infected at an early age may evince signs of disease only at weaning.⁴³

Early signs of S. Choleraesuis-induced septicaemia are usually associated with fever, and may include reduced activity and feed intake, huddling together, and flushing or cyanosis of the skin, particularly of the ventral parts of the body and extremities. Some pigs may die without showing clinical signs of disease. Signs of pneumonia develop in a high percentage of cases, evidenced by dyspnoea and coughing.⁴³ A proportion of pigs that survive longer develop yellowish to greenish watery diarrhoea. Neurological signs resulting from inflammatory processes in the central nervous system are commonly observed in a small percentage of affected pigs.^{43, 50}

In most cases mortality is high, and morbidity variable, usually less than 10 per cent. ¹⁴ Pregnant sows may abort.⁴³ Recovered pigs may suffer relapses, or may become permanently stunted and unthrifty, in some cases progressing to cachexia and death.⁴³

Enterocolitis, either as a result of infection with S. Typhimurium or as a manifestation of S. Choleraesuis infection, is usually characterized by profuse, watery, yellowish to greenish diarrhoea. Sudden death after diarrhoea and vomiting has been described in nine-week-old pigs infected with S. Typhimurium DT104,³⁸ but mortality is usually low and those that do die do so as a result of dehydration. Pigs that develop rectal strictures after recovery from S. Typhimurium enterocolitis generally demonstrate marked emaciation and growth retardation, rough hair coat and intermittent passage of watery, dark faeces; abdominal bloating is frequently present.⁴⁸

Salmonella Choleraesuis has been identified as a cause of porcine pneumonia, which may occur without the other usual manifestations of salmonellosis, presumably when infection occurs via the nasal route.⁴⁶ Hoefling²⁶ reported it to be the second most common cause of porcine bacterial pneumonia in pigs during the nursery and grower period, and noted that it is a common sequel of the disease porcine reproductive and respiratory disease syndrome (PRRS). Clinical signs in these cases are restricted to the respiratory tract, possibly accompanied by fever and inappetence.

Pigs infected with S. Typhisuis become thin and suffer from intermittent diarrhoea, and a firm, symmetrical swelling of the throat may be evident in a proportion of the affected animals.⁵

Pathology

The lesions of the different syndromes of salmonellosis are not pathognomonic. The condition of pigs varies from good in cases of acute disease to poor, stunted and even cachexic when disease has become chronic. The pathology of the different forms of porcine salmonellosis has been described in detail.⁴ Lesions of septicaemic salmonellosis include cyanosis of especially the head, ears and tail, fibrin strands on serosal surfaces, and fluid accumulation in body cavities. The carcass is generally congested, and contains varying numbers of petechiae and ecchymoses. Petechiae are usually present in the kidney cortices, and variably in other organs and tissues. Organs, in particular the spleen, liver and lymph nodes, are swollen. Scattered pinpoint foci of necrosis may be visible in the liver.

Varying degrees of colitis and typhlocolitis, from reddening to frank necrosis of the mucosa, with pseudomembrane formation and ulceration, may be present. Intestinal contents are usually scant and fluid. The presence of ulcers is suggestive of salmonellosis, although the ‘button ulcers’ in the ileum, caecum and colon that have been described are not present in the majority of cases.⁴³

Intestinal lesions in salmonella-induced enterocolitis in the absence of septicaemia vary from mild hyperaemia of the mucosa of the small and large intestine to necrotic or pseudomembranous enterocolitis. Ulceration is reported not to be a feature of enterocolitis induced by S. Typhimurium,⁴ but this organism has been isolated from intestinal ulcers in young weaner pigs in South Africa. In one investigation ulcers were found to be prominent in the colon of pigs infected with S. Typhisuis.⁵ Other lesions of S. Typhisuis infection included necrotic tonsillitis, lymphadenitis of the lymph nodes of the head region, and caseous pneumonia.⁵

Pneumonic lesions may vary from acute interstitial pneumonia with severe oedema and varying degrees of haemorrhage (from petechiae to extensive ecchymosis), to serofibrinous or fibrinous bronchopneumonia with or without pleuritis.^{4, 46} Macroscopic lesions in the brain and spinal cord, when present, are usually restricted to the presence of scattered petechiae.⁴ Rectal strictures, a sequence of chronic proctitis, consist of an annular band of fibrous tissue anterior to the rectal mucocutaneous junction that narrows but does not completely occlude the rectal passage.^{4, 48, 49} Cranial to the stricture, the colon is dilated, with the mucosa ulcerated, covered by a greenish pseudomembrane and filled with gas and pasty ingesta. The lesion is frequently accompanied by fibrinous peritonitis and atrophy of abdominal organs.

Histopathological changes in septicaemic animals include hyperplasia of macrophages including Kupffer cells in the liver, multifocal hepatic necrosis with micro-abscessation or microgranulomas, acute and sometimes suppurative glomerulonephritis, multisystemic necrotic vasculitis and thrombosis, accumulation of macrophages in bronchioli and alveoli of the lungs, and purulent to necrotic enteritis, with macrophages predominating except in the very early stages. Necrosis and ulceration of the intestinal mucosa are generally accompanied by thrombosis. Lesions in the nervous system, when present, usually consist of granulomatous meningoencephalitis, sometimes accompanied by micro-abscesses.⁵⁰

Diagnosis

The diagnosis of salmonellosis requires the isolation and identification of the Salmonella serovar in combination with a clinical syndrome and pathological lesions typical of the condition. It must be emphasized that isolation or detection of salmonellas does not constitute a diagnosis in itself, although the result may be of zoonotic significance.

Bacteriological culture by conventional methods of spleen, liver, kidneys, lungs and intestinal content samples from carcasses, and faeces from clinical cases, should result in a diagnosis. Serological typing of the isolated salmonella is necessary to determine the serovar involved. It has been suggested that failure to culture salmonellas by conventional methods, with the need to resort to special procedures, indicates that the disease was not salmonellosis.⁵²

However, conventional approaches might not lead to the isolation of S. Typhisuis, and more sensitive techniques, such as conventional and delayed enrichment, may also be required to reveal carriers of this and other serovars.^{14, 37} Currently, more rapid methods of detection, in particular the polymerase chain reaction (PCR), permit early detection of salmonellas. A multiplex PCR that detects salmonellas as well as Lawsonia intracellularisis widely available,¹³ including in South Africa. This test, when applied to faecal samples, will detect only pigs that are actually shedding organisms at the time of sampling. Because of its high sensitivity, detection of Salmonella by PCR indicates that the sample was infected, but not that the animal was suffering from salmonellosis. Confirmation of salmonellosis by pathological examination, especially histopathological, is essential, unless the objective is simply to determine whether the pig harboured salmonellas.

An ELISA is used to detect antibodies in serum. While this assay is useful for screening herds for previous exposure, serologically positive pigs are not necessarily carriers of the disease.⁵² There are currently no reliable tests available to detect carriers.

Differential diagnosis

The clinical appearance and gross pathology of septicaemic salmonellosis is similar to that of classical and African swine fever. Morbidity is generally lower than in African swine fever, and, unlike that disease, a particular age group is targeted, and the mortality rate is much lower. There are marked differences in the microscopic pathology of the swine fevers; widespread karyorrhexis of lymphocytes is not a feature of salmonellosis. Other bacterial septicaemias such as pasteurellosis and erysipelas may have a similar presentation, and should be distinguished by bacteriological and histopathological examination.

Enterocolitis caused by S. Typhimurium is likely to have features in common with most causes of diarrhoea in pigs, of which the most important are Escherichia coli infections, swine dysentery, and proliferative enteritis caused by Lawsonia intracellularis. Salmonella Typhimurium mainly affects the hindgut, unlike E. coli and L. intracellularis. When there is ileal involvement, the ileal lesions are less severe than those at and posterior to the ileocaecal junction. The clinical features of enterocolitic salmonellosis differ from those of swine dysentery in that the pigs are ill and inappetent and the faeces are fluid and yellow with blood appearing later rather than earlier in the course of the disease, while pigs suffering from swine dysentery usually appear healthy, although producing pasty, often blood-stained faeces. Necrotic ileitis caused by salmonellosis is easily distinguished histopathologically from that caused by L. intracellularis, which is characterized by proliferation and necrosis of mucosal glands, with loss of mucus cells, and the presence of large numbers of characteristic intracellular bacteria that are visible with silver staining. Gland necrosis is also a feature of salmonellosis, but the lesions are generally more severe, and are accompanied by thrombosis.

Control

Control of Salmonella infection in pig herds is difficult. To date, success with vaccination using bacterins and subunit vaccines has been variable, and the use of these vaccines should form part of a holistic approach to control based on hygienic management.¹⁴ Promising results have been reported with live attenuated strains,^{28, 41} but these are not widely available commercially. No vaccines against porcine salmonellosis are available in South Africa.

Antimicrobial treatment during outbreaks is rarely efficacious,^{14, 52} although reduction in volume and duration of bacterial shedding have been demonstrated.⁵¹ The antimicrobial selected for use should be based on the results of an antibiogram of the Salmonella serovar isolated from a typical case(s) of the disease, as multiple resistance has been demonstrated for many serovars, including strains commonly isolated from pigs. Salmonella Typhimurium DT104 strains are usually resistant to ampicillin, chloramphenicol, streptomycin, sulphonamides and tetracycline, and a low proportion has also been found to be resistant to trimethoprim and ciprofloxacin.³⁸ The propensity of some strains to develop multiple resistance has given rise to serious concerns particularly about the prophylactic use of antimicrobials administered at lower dosage levels in feed,²³⁸ The inclusion of antimicrobials in the feed of pigs is not generally regarded as a sustainable method of controlling salmonellosis, although it may prevent clinical disease from developing.⁵²

Hygienic measures are extremely important, as it has been demonstrated that infection in finisher pigs is more likely to be due to exposure to contamination during the growing period than to infection from the breeder herd.⁸ While salmonellosis is considered to be more likely to occur in continuous flow management systems,⁴³ the results of some studies suggest that all-in-all-out management does not necessarily prevent Salmonella infection.^{9, 11} However, elimination of infection has been achieved by strategic movement of pigs to clean facilities, as well as early weaning (14 to 21 days) with removal from the sow herd.^{8, 14}

Eradication of S. Typhimurium from herds involves drastic measures, as have been implemented in Denmark. Poultry and other birds including pigeons and pheasants, serologically positive pigs, and cats and rodents were destroyed on a wide scale, and on one farm even the farmer’s dog was killed when it was found to be shedding salmonellas.³⁶ Since reinfection is likely, such measures may not be justified.

Assuming that a proportion of slaughter pigs will be infected, measures are needed to prevent introduction of Salmonella into the human food chain by minimizing shedding of salmonellas before slaughter. Studies have shown that pigs held for 24 hours in lairages did not shed salmonellas, while those slaughtered within two to three hours of delivery to the abattoir had a higher rate of shedding.¹⁴ On the other hand, extended holding periods have been demonstrated to increase shedding.³³ Withholding feed for 24 hours before transportation also reduced the number of pigs shedding salmonellas.²⁷ If the sterility of rendered animal waste products used in animal feeds is maintained, this will assist in breaking the cycle of Salmonella infection in food animals.³⁸

Various strategies have been found to reduce the prevalence of Salmonella infection in feed, including feeding wet rather than dry feed, mixing feed with whey rather than water, using naturally fermented feed, and acidifying feed.¹⁴ Since contamination that does not involve active shedding may occur at various points in the slaughter process, hygienic procedures are essential. It has been demonstrated that the employment of hazard analysis of critical contact point (HACCP) principles during the slaughter process has reduced the recovery of salmonellas from slaughtered pigs.¹⁴

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