Overview of Salmonellosis
Salmonella, a rod-shaped gram-negative bacterium belonging to the family Enterobacteriaceae, is the causative agent of salmonellosis. Salmonellosis in warm-blooded vertebrates is in most cases associated with serovars of Salmonella enterica. The most common type of infection is the carrier state, in which infected animals carry the pathogen for a variable period of time without showing any clinical signs. Clinical disease is characterized by two major syndromes: a systemic septicemia (also termed as typhoid) and an enteritis. Other less common clinical presentations include abortion, arthritis, respiratory disease, necrosis of extremities, and meningitis.
Only a few serotypes produce clinical salmonellosis in healthy animals and typically have a narrow range of host species, a phenomenon termed serovar-host specificity. 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.
The remaining serovars (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 people (nontyphoidal salmonellosis) but 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 their dam or when they are particularly susceptible, eg, as a result of old age, disease, 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.
Young calves, piglets, lambs, and foals may develop both the enteritis and septicemic form (see Diarrhea in Neonatal Ruminants, see Bacterial Diarrhea in Foals, and see 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, Intestinal Diseases in Cattle, 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.
Salmonellosis has been recognized in all parts of the world but is most prevalent in regions with intensive animal husbandry. Although this facultative intracellular pathogen is primarily an intestinal bacterium, it is commonly found in an environment subject to fecal contamination. 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.
Although 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:z4:z23; 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. 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 administration of certain drugs, including oral antibiotics. Greater susceptibility in the very young may be the result of high gastric pH, absence of a stable intestinal flora, and limited immunity.
The usual route of infection in enteritis is fecal-oral, although infection through the upper respiratory tract and the conjunctiva have also been reported. After ingestion, the organism colonizes the digestive tract and invades and multiplies in enterocytes and tonsillar lymphoid tissue. 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. Some serotypes also become localized in the reproductive tract. 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, joints and 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 may 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.
In cattle, S Typhimurium is commonly associated with outbreaks of enteritis in calves <2 mo old, whereas S Dublin has been associated with the same condition in older calves and adult cattle. 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.
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. Passerines, gulls, and pigeons can present a direct source of infection or a source of contamination of feed and water.
Most cases in adult horses 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 Intestinal Diseases in Horses and Foals.)
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.
Infection with localization of the pathogen in tonsils or the GI tract that is not associated with clinical disease is a common form of salmonellosis termed as the carrier state. Carrier animals are chronically infected and may shed salmonellae intermittently into the environment. Carrier animals can develop clinical disease whenever the immune function is compromised or concurrent infection with another pathogen occurs.
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 ≥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 of salmonellosis depends on clinical signs and isolation of the pathogen from feces, blood, 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 to determine the source of the organism. 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 tests are available and are increasingly used as a diagnostic tool in salmonellae surveillance and control programs. These tests are normally developed to identify a limited spectrum of salmonellae serovars and serogroups. Serologic tests are difficult to interpret in individual animals, because a seropositive animal may no longer be infected. Furthermore, specificity issues mean that in countries with low infection prevalence, many positive results are false-positive.
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, ostertagiosis, 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 intracellularis, classical swine fever, and pasteurellosis); horses—septicemia (due to E coli, Actinobacillus equuli, or streptococci); poultry—coliform enteritis and Yersinia pseudotuberculosis.
Lesions are most severe in the lower ileum, cecum, and spiral colon and vary from shortening of villi with loss of the epithelium to complete loss of intestinal architecture. There is infiltration of the lamina propria with neutrophils and later with macrophages, and thrombi may be seen in capillaries in this region. Hemorrhage and fibrin strands are usually seen, and there may be a fibrinonecrotic crust on the surface of the intestinal mucosa. 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 nonselective 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.
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 administered systemically are indicated for treatment of 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.
If oral medication is chosen, it should be given in drinking water and not mixed into solid feed, 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 NSAIDs or flunixin meglumine may be used to reduce the effects of endotoxemia.
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. A concern with antimicrobial therapy is that it may increase the risk of creating carrier animals; in people and other animal species, antimicrobial therapy prolongs the period after clinical recovery during which the pathogen can be retrieved from the GI tract.
Carrier animals and contaminated feedstuffs and environment are major problems. 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.
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.
In an outbreak of salmonellosis, 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 they are not carriers. 2) The prophylactic use of antibiotics in feed or water supplies may be considered (the hazards are mentioned earlier). 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 below). 9) Stresses should be minimized.
Salmonellae are facultative intracellular bacteria, 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 licensed for use in swine appears to effectively reduce colonization of tissues and protect 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.
Infections with Salmonella in food-producing animals present a serious public health concern, because food products of animal origin are considered to be a significant source of human infection. Most common sources of infection are eggs and related products, and meat from poultry and other food animal species (see Salmonelloses). Milk and dairy products have also been associated with outbreaks of salmonellosis in people. In addition, contamination of fruit and vegetables by infected water may also be a source of infection. In Europe, S Enteritidis and S Typhimurium, and in the USA, S Typhimurium are the most prevalent serovars associated with human disease.