SALMONELLA TYPHIMURIUM AND S. I 4,[5],12:i:- (ENTERIC SALMONELLOSIS)

LEVELS: Likely to occur: Effective control measures not fully understood; Occupational exposure risk: Non-foodborne transmission pathway(s) that are strongly associated with occupational exposure and can lead to human infection; Unlikely to be effective: One or more pathways of farm-to-farm transmission exist that cannot be controlled by on-farm biosecurity; Easy: Distinct clinical signs and/or existing test(s) available at local/regional laboratory(s); Moderate: Manageable losses related to endemic (population) or chronic (individual) occurrence; Negligible: Little or no market disruption when disease occurs on one or more farms; High risk: Resistance to antibacterial or antiviral treatments is, or can be expected to be a common problem; Moderate risk: Antibacterial or antiviral treatments are commonly used for treating affected individuals; Available but with uncertain efficacy: Limited treatments available in US or are only effective in some situations; Available but uncertain efficacy: Commercial or autogenous vaccines exist in the US but protection may be inconsistent; Not feasible: Eradication extremely unlikely


OVERVIEW

Salmonella Typhimurium and its monophasic variant S. I 4,[5],12:i:- are generalist serovars causing enteric salmonellosis (enterocolitis) in pigs, characterized by watery yellow diarrhea affecting pigs 3-10 weeks of age. S. I 4,[5],12:i:- has emerged as the most frequently isolated serovar from diseased US pigs, surpassing S. Typhimurium. The monophasic variant lacks phase 2 flagellar antigens and has acquired metal tolerance genes (copper, silver, arsenic, mercury) that may provide competitive advantage in production environments. It also carries the ASSuT multidrug resistance module. Diarrhea typically lasts 3-7 days, may recur, and mortality is usually low. Gross lesions include fibrinonecrotic enterotyphlocolitis primarily affecting the spiral colon, with markedly enlarged mesenteric lymph nodes. Chronic lesions include characteristic "button ulcers." Both serovars are significant foodborne zoonotic pathogens; S. I 4,[5],12:i:- is the most frequent non-typhoidal multidrug-resistant serovar causing human illness. Sixteen of the top 20 human Salmonella serovars are isolated from swine.


FOODBORNE ZOONOTIC TRANSMISSION POTENTIAL

Level: Likely to occur: Effective control measures not fully understood

Major foodborne pathogen: (1) Leading cause of illness: "Non-typhoidal salmonellosis is a global public health problem and is a leading cause of foodborne illness in the United States and worldwide"; (2) Human illness burden: "an estimated 1.35 million human illnesses occur annually, resulting in approximately 400 deaths and an economic burden of $4.1 billion"; (3) Pork contamination: "approximately 9% of pork cuts and approximately 30% of comminuted pork samples testing positive for Salmonella"; (4) Shared serovars: "16 of the top 20 Salmonella serovars isolated from human illnesses are also isolated from swine."


NON-FOODBORNE ZOONOTIC TRANSMISSION POTENTIAL

Level: Occupational exposure risk: Non-foodborne transmission pathway(s) that are strongly associated with occupational exposure and can lead to human infection

Direct contact transmission documented: (1) Direct exposure: "direct contact with clinically or subclinically infected animals can also be a source of human infection"; (2) Human disease: "Non-typhoidal human salmonellosis usually manifests as self-limiting diarrhea, abdominal cramps, vomiting, and fever"; (3) Severe outcomes possible: "Severe disease and mortality can occur in infants, the elderly, or immunocompromised individuals."


EFFECTIVENESS OF ON-FARM BIOSECURITY IN PREVENTING FARM-TO-FARM TRANSMISSION

Level: Unlikely to be effective: One or more pathways of farm-to-farm transmission exist that cannot be controlled by on-farm biosecurity

Ubiquitous with multiple transmission routes: (1) High prevalence: "After arrival on the farm or commingling, infection with Salmonella usually occurs within the first few weeks and reaches a maximum of 80–100% prevalence"; (2) Aerosol transmission: "Aerosol transmission is likely with dispersion of secretions, feces, or contaminated dust particles"; (3) Multiple sources: "potential sources of contamination include water supplies, feed, and vectors in the production environment such as insects, rodents, migratory birds"; (4) Carrier state: "approximately 5–30% of pigs still excreting Salmonella at the end of the finishing period."


DIFFICULTY OF DETECTING AND CONFIRMING INFECTION

Level: Easy: Distinct clinical signs and/or existing test(s) available at local/regional laboratory(s)

Multiple diagnostic tools available: (1) Characteristic lesions: Fibrinonecrotic enterotyphlocolitis, button ulcers, enlarged mesenteric lymph nodes; (2) Culture available: Multiple selective media; "Samples from clinically affected animals are preferably collected during the acute phase"; (3) PCR available: "Molecular assays such as real-time PCR are a valuable screening tool"; multiplex PCR can differentiate S. Typhimurium and I 4,[5],12:i:-; (4) Serology available: "Multiple commercial enzyme-linked immunosorbent assays (ELISAs) are available."


FINANCIAL IMPACT ON FARM'S COST OF PRODUCTION

Level: Moderate: Manageable losses related to endemic (population) or chronic (individual) occurrence

Lower mortality but production impacts: (1) Low mortality: "Mortality is usually low and occurs only after several days of diarrhea"; (2) Morbidity: "The disease may spread rapidly to involve most pigs in a pen within a few days"; (3) Waxing and waning: "the impression of a waxing and waning diarrheal disease lasting several weeks"; (4) Chronic wasting: "A few pigs may remain unthrifty and chronically wasted."


EFFECT ON DOMESTIC OR EXPORT MARKETS

Level: Negligible: Little or no market disruption when disease occurs on one or more farms

Food safety concern but no trade restrictions: (1) Pre-harvest programs: Food safety initiatives focus on reducing contamination; (2) Endemic: Present in all swine-producing regions; (3) Processing contamination: Major concern at processing rather than live animal trade.


PATHOGEN'S ABILITY TO DEVELOP AND SPREAD RESISTANCE

Level: High risk: Resistance to antibacterial or antiviral treatments is, or can be expected to be a common problem

Significant MDR concerns, especially S. I 4,[5],12:i:-: (1) MDR emergence: "S. I 4,[5],12:i:- being the most frequent non-typhoidal multidrug-resistant serovar"; (2) ASSuT resistance: "genes for resistance to ampicillin, streptomycin, sulfisoxazole, and tetracycline (R-type ASSuT)"; (3) Metal tolerance co-selection: "exposure to one stressor (e.g. heavy metals) selects for the maintenance of the other module (antibiotic resistance)"; (4) CDC classification: "classified antibiotic-resistant Salmonella as a serious threat."


AMR DEVELOPMENT DRIVEN BY DISEASE MANAGEMENT

Level: Moderate risk: Antibacterial or antiviral treatments are commonly used for treating affected individuals

Antimicrobials commonly used: (1) Treatment warranted: "A salmonellosis diagnosis of clinically ill pigs warrants immediate treatment"; (2) Mass treatment: "Mass treatment of the population at risk is routinely practiced"; (3) Co-selection concern: Metal use in production may co-select for antibiotic resistance in S. I 4,[5],12:i:-.


AVAILABILITY OF EFFECTIVE TREATMENT OPTIONS

Level: Available but with uncertain efficacy: Limited treatments available in US or are only effective in some situations

Treatment effective but with limitations: (1) Effective drugs: "gentamicin, neomycin, apramycin, ceftiofur, and trimethoprim-sulfonamide have been effective"; (2) Sensitivity testing needed: "data-based decision-making using antibiotic sensitivity testing of cultured isolates"; (3) Intracellular survival: "the ability of Salmonella to inhabit protected intracellular niches in the host can hinder the accessibility of many antimicrobials."


AVAILABILITY OF EFFECTIVE VACCINES OR BACTERINS

Level: Available but uncertain efficacy: Commercial or autogenous vaccines exist in the US but protection may be inconsistent

Vaccines available with variable efficacy: (1) Live vaccines: "Vaccination with attenuated, live vaccines that stimulate cell-mediated immunity...has also shown effectiveness against enterocolitis due to S. Typhimurium"; (2) Combination vaccine: "A vaccine containing both S. Choleraesuis and S. Typhimurium is also available and has been shown to significantly reduce S. I 4,[5],12:i:- fecal shedding"; (3) Killed vaccines limited: "Killed vaccines for S. Typhimurium are safe, but evidence suggests that they have little efficacy in preventing disease following strong challenge."


FEASIBILITY OF ERADICATING THE DISEASE FROM THE US

Level: Not feasible: Eradication extremely unlikely

Eradication not feasible: (1) Ubiquitous: "Most swine herds are colonized with one or more serovars of Salmonella"; (2) Generalist serovar: Infects wide range of host species; (3) Environmental persistence: Multiple reservoirs and vectors; (4) Carrier state: Prolonged shedding; "over 90% of pigs were positive for S. Typhimurium in the mesenteric lymph node, tonsil, cecum, or feces" 4-7 months post-inoculation.