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Salmonellosis is caused by many serotypes of Salmonella enterica enterica and characterized clinically by 2 major syndromes—a systemic septicemia/typhoid and an enteritis—although disease-free infections also undoubtedly occur.
A small number of serotypes are characterized by the ability to produce clinical typhoid in healthy, adult individuals in a typically narrow range of host species. Thus, Salmonella enterica serovar typhi (S typhi) and S paratyphi produce typhoid in people, S gallinarum produces a similar disease in poultry, S abortusovis in sheep, S choleraesuis in pigs, S dublin in cattle, etc. In this infection, transmission is generally by the oral route. The bacteria do not colonize the gut extensively but penetrate the intestinal wall and are taken up by cells of the monocyte-macrophage line in the spleen and liver, where they multiply. In the later stages of clinical disease, they re-enter the gut from where they are shed. Some serotypes also become localized in the reproductive tract.
The remaining serotypes rarely produce clinical systemic disease in healthy, adult, nonpregnant animals. However, they colonize in the gut of many species of animals, enter the human food chain, and produce gastroenteritis in people (food poisoning). S typhimurium and S enteritidis are the most frequent causes of enteritis in man and, interestingly, they are also able to produce typical typhoid infections in mice; hence, the basis of pathogenicity is unclear. Strains from this latter group may also produce more severe disease with systemic involvement resembling typhoid in very young animals if they have received insufficient protective antibody from the dam or when they are particularly susceptible, eg, as a result of extreme age or pregnancy. The host species from which a serotype is characteristically isolated is not necessarily the only species that can act as a host; thus, epidemiologic factors are important in determining prevalence.
Enteritis is seen worldwide and in all animals. Incidence has increased with intensification of livestock production. Young calves, piglets, lambs, and foals may develop both the enteritis and septicemic form (see Intestinal Diseases in Ruminants: Diarrhea in Neonatal Ruminants, see Intestinal Diseases in Horses and Foals: Bacterial Diarrhea in Foals, and see Intestinal Diseases in Pigs: Intestinal Salmonellosis in Pigs). Adult cattle, sheep, and horses commonly develop acute enteritis, and chronic enteritis may develop in growing pigs and occasionally in cattle (see also the chapters on intestinal diseases in each of the major domestic species, see Intestinal Diseases in Ruminants et seq). Pregnant animals may abort. The clinically normal carrier animal is a serious problem in all host species. Salmonellosis is seen infrequently in dogs and cats and is characterized by acute diarrhea with or without septicemia.
Etiology and Pathogenesis
While many other Salmonella spp may cause enteric disease, the more common ones (to some extent varying according to geographic location) in each species are as follows: Cattle—S typhimurium, S dublin, and S newport; Sheep and Goats—S typhimurium, S dublin, S abortusovis, S anatum , and S montevideo; Pigs—S typhimurium and S choleraesuis; Horses—S typhimurium, S anatum, S newport, S enteritidis, and Salmonella serovar IIIa 18:z4z23; and Poultry—S enteritidis, S typhimurium, S gallinarum, and S pullorum.
Although their resulting clinical patterns are not distinct, different species of salmonellae do tend to differ in their epidemiology. Plasmid profile and drug-resistance patterns are sometimes useful markers for epidemiologic studies. Feces of infected animals can contaminate feed and water, milk, fresh and processed meats from abattoirs, plant and animal products used as fertilizers or feedstuffs, pasture and rangeland, and many inert materials. The organisms may survive for months in wet, warm areas such as in feeder pig barns and poultry houses or in water dugouts, but they survive <1 wk in composted cattle manure. Rodents and wild birds are also sources of infection for domestic animals. Pelleting of feeds reduces the level of contamination by salmonellae largely as a result of the heat treatment involved.
The prevalence of infection varies among host species and countries and is much higher than the incidence of clinical disease, which in food animals is commonly precipitated by stressful situations such as sudden deprivation of feed, transportation, drought, crowding, parturition, surgery, and the administration of certain drugs, including oral antibiotics administered therapeutically, prophylactically, or for growth stimulation.
The usual route of infection in enteritis is oral and, after infection, the organism multiplies in the intestine and causes enteritis. Greater susceptibility in the very young may be the result of high gastric pH, absence of a stable intestinal flora, and limited immunity. Penetration of bacteria into the lamina propria contributes to gut damage and diarrhea. The complex process involves attachment through fimbrial appendages and the injection by the attached Salmonella organisms into epithelial cells of proteins, which induce changes in the actin cytoskeleton that induce membrane ruffling at the cell surface. This entraps the Salmonella bacteria and results in fluid secretion and their ingestion by the cell. The cellular infection results in activation of a host alarm process through signalling molecules as a result of the detection of bacterial surface proteins, which in turn induces a strong inflammatory response that generally is able to restrict the bacteria to the intestine. Serotypes that are able to cause typhoid can modulate the initial host response and suppress the inflammatory response. Cell destruction follows, and the bacteria are ingested by phagocytic cells such as macrophages and neutrophils. Although neutrophils are generally able to kill Salmonella, the bacteria can survive and multiply within macrophages, which represent the main host cell type during infection.
As infection progresses, a true septicemia may follow with subsequent localization in brain and meninges, pregnant uterus, distal aspects of the limbs, and tips of the ears and tails, which can result, respectively, in meningoencephalitis, abortion, osteitis, and dry gangrene of the feet, tail, or ears. The organism also frequently localizes in the gallbladder and mesenteric lymph nodes, and survivors intermittently shed the organism in the feces.
Calves rarely become carriers but virtually all adults do for variable periods—up to 10 wk in sheep and cattle and up to 14 mo in horses. Adult cattle infected with S dublin excrete the organism for years. Infection may also persist in lymph nodes or tonsils, with no salmonellae in the feces. Latent carriers may begin shedding the organism or even develop clinical disease under stress. A passive carrier acquires infection from the environment but is not invaded, so that if removed from the environment, it ceases to be a carrier.
Epidemiology
Cattle and Sheep
In calves and lambs, S dublin is usually endemic on a particular farm, whereas S typhimurium is frequently associated with introduction of calves from infected farms and may cause sporadic explosive outbreaks. Subclinical infection with occasional herd outbreaks may be seen in adult cattle. Stressors that precipitate clinical disease include deprivation of feed and water, minimal levels of nutrition, long transport times, calving and antibiotic prophylaxis, and mixing and crowding in feedlots.
Pigs
Outbreaks of septicemic salmonellosis in pigs are rare and usually can be traced to a purchased, infected pig. Purchase of feeder pigs from Salmonella-free herds and use of the “all-in/all-out” policy in finishing units minimize exposure. Increasing use of extensive outdoor rearing increases the risk of exposure to environmental sources of infection.
Horses
Most cases in adults develop after the stress of surgery or transport related to sales yards and deprivation of feed and water followed by overfeeding at their destination. Mares may be inapparent shedders and shed the bacteria at parturition, infecting newborn foals. Septicemic salmonellosis may occur in foals, which may be endemic or there may be outbreaks. (see also Intestinal Diseases in Horses and Foals.)
Dogs and Cats
Many dogs and cats are asymptomatic carriers of salmonellae. Clinical disease is uncommon, but when it is seen, it is often associated with hospitalization, another infection or debilitating condition in adults, or exposure to large numbers of the bacteria in puppies and kittens, in which enteritis may be common.
Clinical Findings
Enteritis with septicemia is the usual syndrome in newborn calves, lambs, foals, fowl, and piglets, and outbreaks may occur in pigs up to 6 mo old. When systemic disease occurs with enteritis as a result of insufficient immunity, illness may be acute with depression, fever (105–107°F [40.5–41.5°C]), and death in 24–48 hr. Nervous signs and pneumonia may be seen in calves and pigs. Mortality may reach 100%, depending on the host genetic background and strain virulence.
Acute enteritis without extensive systemic involvement is more common in adults as well as in young animals that are ≥1 wk old. Initially, there is fever (105–107°F [40.5–41.5°C]), followed by severe watery diarrhea, sometimes dysentery, and often tenesmus. In a herd outbreak, several hours may lapse before the onset of diarrhea, at which time the fever may disappear. The feces, which vary considerably in consistency, may have a putrid odor and contain mucus, fibrinous casts, shreds of mucous membrane, and in some cases, blood. Rectal examination causes severe discomfort and tenesmus. Milk production often declines precipitously in dairy cows. Abdominal pain is common and may be severe (colic) in horses. Mortality is variable but may reach 100% depending on strain virulence. A marked leukopenia and neutropenia are characteristic of the acute disease in horses. In dogs and cats, clinical disease takes the form of acute diarrhea with septicemia and is seen occasionally in puppies and kittens or in adults stressed by concurrent disease. Pneumonia may be evident. When the enteritis becomes more chronic, abortion may occur in pregnant dogs, cats, cattle, horses, and sheep, and live progeny may have enteritis as well. Conjunctivitis is sometimes seen in affected cats.
Fur-bearing and zoo carnivores may be affected. Contaminated feed is often the source of infection. Several rodent species (eg, guinea pigs, hamsters, rats, and mice) and rabbits are susceptible. Rodents commonly act as a source of infection on farms where the disease is endemic. Pet turtles were once a common source of infection in people that has been virtually eliminated by the curtailment of commercial trafficking.
Diagnosis
Diagnosis depends on clinical signs and on the isolation of the pathogen from feces or tissues of affected animals. The presence of organisms may also be sought in feed, water supplies, and feces from wild rodents and birds that may inhabit rearing premises.
The clinical syndromes usually are characteristic but must be differentiated from several similar diseases in each species as follows: Cattle—diarrhea due to enterotoxigenic Escherichia coli, dysentery due to verotoxigenic E coli, coccidiosis, cryptosporidiosis, the alimentary tract form of infectious bovine rhinotracheitis, bovine viral diarrhea, hemorrhagic enteritis due to Clostridium perfringens types B and C, arsenic poisoning, secondary copper deficiency (molybdenosis), winter dysentery, paratuberculosis, ostertagiasis, and dietetic diarrhea; Sheep—enteric colibacillosis, septicemia due to Haemophilus sp or pasteurellae, and coccidiosis; Pigs—enteric colibacillosis and Clostridium difficile of newborn pigs and weanlings, swine dysentery (Brachyspira hyodysenteriae), campylobacteriosis, and the septicemias of growing pigs (which include erysipelas, Lawsonia intracellulare, classical swine fever, and pasteurellosis); Horses—septicemia (due to E coli, Actinobacillus equuli, or streptococci); Poultry—coliform enteritis and Yersinia pseudotuberculosis.
Lesions
Lesions are most severe in the lower ileum and the large intestine and vary from shortening of villi with loss of the epithelium to complete loss of intestinal architecture. There is a neutrophilic reaction in the lamina propria, and thrombi may be seen in blood vessels in this region. Hemorrhage and fibrin strands are usually seen. Culture techniques that involve suppression of fecal E coli are usually necessary, and several daily fecal cultures may be necessary to isolate the organism. A non-selective enrichment stage may be required for samples in which bacteria may be present in low numbers, as in foodstuffs. This may be followed by enrichment in selective broth and plating for colonies on a variety of selective agars that suppress other enteric bacteria likely to be present in the gut. Blood cultures in septicemic animals may be rewarding but are costly.
Bacteria are usually identified by a range of biochemical tests. Identification to serotype may be done followed by further subdivision on the basis of susceptibility to selected bacteriophages (phage typing).
Serologic testing is difficult to interpret for individual animals. It is used extensively through ELISA to monitor poultry flocks for the presence of infection by serotypes such as S enteritidis, S typhimurium, and S gallinarum/S pullorum and to detect antibodies in pig meat juice at slaughter.
Treatment
Early treatment is essential for septicemic salmonellosis, but there is controversy regarding the use of antimicrobial agents for intestinal salmonellosis. Oral antibiotics may be ineffective and may deleteriously alter the intestinal microflora, thereby interfering with competitive antagonism and prolonging shedding of the organism. There is also concern that antibiotic-resistant strains of salmonellae selected by oral antibiotics may subsequently infect people. By suppressing antibiotic-sensitive components of the normal flora, antibiotics may also promote transfer of antibiotic resistance from resistant strains of E coli to Salmonella. Use of chemotherapeutic antibiotics for growth stimulation has been banned in many countries for this reason.
Broad-spectrum antibiotics may be used parenterally to treat septicemia. Initial antimicrobial therapy should be based on knowledge of the drug resistance pattern of the organisms previously found in the area. Nosocomial infections may involve highly drug-resistant organisms. Trimethoprim-sulfonamide combinations may be effective. Alternatives are ampicillin, fluoroquinolones, or third-generation cephalosporins. Resistance to ampicillin, trimethoprim, sulfonamide, tetracyclines, and aminoglycosides is generally plasmid mediated and transfers readily between different bacteria. Resistance to quinolones is mutational, but random mutations may be selected by antibiotic use and may be transferred by bacteriophages. Treatment should be continued daily for up to 6 days.
Oral medication should be given in drinking water because affected animals are thirsty due to dehydration, and their appetite is generally poor. Fluid therapy to correct acid-base imbalance and dehydration may be necessary. Calves, adult cattle, and horses need large quantities of fluids. Antibiotics such as ampicillin or cephalosporins lead to lysis of the bacteria with release of endotoxin, and NSAID or flunixin meglumine may be used to reduce the effects of endotoxemia. Animals may become acidotic and hyponatremic and require appropriate treatment. Animals may become acidotic and hyponatremic and require appropriate treatment.
The intestinal form is difficult to treat effectively in all species. Although clinical cure may be achieved, bacteriologic cure is difficult, either because the organisms become established in the biliary system and are intermittently shed into the intestinal lumen, or because the animals are reinfected from the environment at a time when their normal gut flora, which is inhibitory to colonization by pathogens, is depleted by antibiotic therapy. Ideally, therapy should be followed by oral administration of a pathogen-free culture of species-specific gut bacteria.
Control and Prevention
These are major problems because of carrier animals and contaminated feedstuffs and environment. Drain swabs or milk filters may be cultured to monitor the salmonellae status of a herd. The principles of control include prevention of introduction and limitation of spread within a herd. In many countries and in the EU, government-backed programs have been introduced to control and reduce levels of infection in food animals, especially poultry and pigs.
Prevention of Introduction
Every effort must be made to prevent introduction of a carrier; ideally, animals should be purchased directly only from farms known to be free of the disease and should be isolated for ≥1 wk while their health status is monitored. Ensuring that feed supplies are free of salmonellae depends on the integrity of the source. Some countries also test for contamination of and regulate importation and home production of feedstuffs and feed components.
Limitation of Spread Within a Herd
In an outbreak, the following procedures should be implemented: 1) Carrier animals should be identified and either culled or isolated and treated vigorously. Treated animals must be rechecked several times before there can be confidence that they are not carriers. 2) The prophylactic use of antibiotics in feed or water supplies may be considered (the hazards are mentioned above). 3) Movement of animals around the farm should be restricted to limit infection to the smallest group. Random mixing of animals should be avoided. 4) Feed and water supplies must be protected from fecal contamination. 5) Contaminated buildings must be vigorously cleaned and disinfected. 6) Contaminated material must be disposed of carefully. 7) All persons should be aware of the hazards of working with infected animals and the importance of personal hygiene. A strict farm management program should be introduced. 8) Use of a vaccine should be considered, particularly in an outbreak involving pregnant cattle, pigs, or laying poultry. Commercial killed bacterins or autogenous bacterins may be used. Live attenuated vaccines show considerable promise, but few are available commercially (see Salmonellosis: Salmonella Vaccines). 9) Stresses should be minimized.
Salmonella Vaccines
Salmonellae are intracellular parasites, and a live vaccine is therefore expected to be necessary for optimal immune protection against disease; however, there is some evidence that inactivated bacterins can induce a lower level of protection. In several studies, live attenuated Salmonella vaccines in pigs, cattle, and chickens stimulated a strong cell-mediated immune response and protected animals against both systemic disease and intestinal colonization. A live attenuated S choleraesuis vaccine that has been licensed for use in swine appears to be effective in reducing colonization of tissues and protecting pigs from disease after challenge with virulent organisms and under field conditions. This vaccine also protected calves against experimental challenge with S dublin and serogroup C1 salmonellae after intranasal or SC administration. A live S gallinarum vaccine has been shown to be effective not only against S gallinarum (fowl typhoid) but also in significantly reducing the infection of laying hens challenged with S enteritidis.
Zoonotic Risk
The incidence of human enteric salmonellosis has increased in recent years, and animals have been incriminated as the principal reservoir. Transmission to people occurs via contaminated drinking water, milk, meat, and processed foods and their ingredients; poultry and eggs (see Salmonelloses) are particularly important sources of infection. In addition, contamination of fruit and vegetables by infected water may also be a source of infection.
Last full review/revision March 2012 by P.A. Barrow, PhD, DSc, FRCPath
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