CLOSTRIDIOIDES DIFFICILE
LEVELS: Rarely occurs: Requires significant failure at one or more control points for transmission to humans; Highly unlikely: No evidence of non-foodborne zoonotic transmission; Highly effective: Routine on-farm biosecurity measures are effective in preventing farm-to-farm transmission; 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; Moderate risk: Evidence of development of clinically important resistance to antibacterial or antiviral treatments, or that development of such resistance is likely to occur over time; Minimal risk: Antibacterial or antiviral treatments rarely occur, or are typically limited to short-course individual animal therapy; Available but with uncertain efficacy: Limited treatments available in US or are only effective in some situations; No availability: Effective vaccines not currently available in the US (or have not been developed); Not feasible: Eradication extremely unlikely
OVERVIEW
Clostridioides difficile (formerly Clostridium difficile) is a gram-positive, strictly anaerobic, spore-forming rod that causes necrotizing enterotyphlocolitis in neonatal piglets, typically presenting at 1-7 days of age. Unlike CDAD in most species, the disease in pigs is NOT antibiotic-associated. Disease is mediated by toxins A (TcdA) and B (TcdB), with a possible role for binary toxin (CDTa). Clinical signs include diarrhea, respiratory distress, mild abdominal distension, scrotal edema, or sudden death. Characteristic lesions include mesocolonic edema and necrosuppurative typhlocolitis with "volcano lesions"—multifocal erosions through which fibrin and neutrophils exude. C. difficile colonization in piglets is extremely common (100% by 3 days of age) but prevalence decreases dramatically in older pigs (3-9%). The organism's highly resistant spores are ubiquitous in environments subject to fecal contamination and resist most common disinfectants. C. difficile ribotype 078, common in pigs, is also among the most frequently isolated strains in multidrug-resistant human CDAD, raising potential zoonotic concerns, though direct transmission from pigs to humans has not been confirmed. No commercial vaccines are available for swine.
FOODBORNE ZOONOTIC TRANSMISSION POTENTIAL
Level: Rarely occurs: Requires significant failure at one or more control points for transmission to humans
The zoonotic/foodborne risk is theoretically possible but not confirmed: (1) Shared ribotype: "C. difficile ribotype 078 is among the most commonly isolated strains in cases of multidrug-resistant, nosocomial, and CA-CDAD in humans. Pigs are a reservoir of this ribotype, and genetically indistinguishable strains have been detected both in pigs and humans"; (2) Meat contamination uncommon: "Contamination of carcasses at slaughter is uncommon, and foodborne transmission is unlikely"; (3) No confirmed transmission: "Direct transmission from human carriers or from infected animals has also not been confirmed as a direct cause of CDAD"; (4) Community-acquired uncertainty: "Source of infection in CA-CDAD is usually unknown. Recent attention has focused on zoonotic or foodborne sources" but no definitive link established.
NON-FOODBORNE ZOONOTIC TRANSMISSION POTENTIAL
Level: Highly unlikely: No evidence of non-foodborne zoonotic transmission
Direct zoonotic transmission is plausible but unconfirmed: (1) Shared strains: "genetically indistinguishable strains have been detected both in pigs and humans, including samples from farm workers"; (2) Not confirmed: Despite shared strains, "Direct transmission from human carriers or from infected animals has also not been confirmed as a direct cause of CDAD"; (3) Environmental ubiquity: C. difficile "can be found in surprisingly large numbers in any environment subject to fecal contamination"—making source attribution difficult; (4) Human risk factors differ: CA-CDAD "occurs in young persons without contact with hospital or clinical environments but with frequent use of proton inhibitors"—not associated with animal contact.
EFFECTIVENESS OF ON-FARM BIOSECURITY IN PREVENTING FARM-TO-FARM TRANSMISSION
Level: Highly effective: Routine on-farm biosecurity measures are effective in preventing farm-to-farm transmission
While spores are highly resistant, disease is contained within farm operations: (1) Neonatal infection: Occurs in piglets 1-7 days old; older pigs are resistant; (2) Spore resistance: "spores of C. difficile are resistant to most common disinfectants, which makes them a sturdy environmental contaminant"; (3) Multiple sources: "primary source of infection for newborn pigs is spores shed in sow feces or in the contaminated local environment"; (4) Airborne possible: "spores have also been found in air samples in swine farms, suggesting that inhalation is possible"; (5) Age-related resistance: "The prevalence decreases dramatically in nursery-age and older pigs, ranging between 3 and 9%"; "Changes in the intestinal microbiota in piglets from 1 week of age may be the cause of the age-related resistance." Standard management of farrowing facilities can reduce exposure.
DIFFICULTY OF DETECTING AND CONFIRMING INFECTION
Level: Easy: Distinct clinical signs and/or existing test(s) available at local/regional laboratory(s)
Diagnosis relies on toxin detection combined with clinical findings: (1) Presumptive diagnosis: Based on "compatible clinical history, clinical signs, and gross and microscopic findings"; "mesocolonic edema and necrosuppurative typhlocolitis with 'volcano lesions' are highly suggestive"; (2) Definitive diagnosis: "must be based on detection of TcdA, TcdB, or both in feces or colonic contents"; (3) Commercial assays: "most laboratories now use commercially available enzyme immunoassays"; (4) Reference method: "measurement of neutralizable cytotoxicity in monolayers of Chinese hamster ovary or other cells"; (5) Sample stability: TcdB "remains unaltered after 21 days of storage both at 4°C and −30°C"; TcdA less stable; (6) Culture limitations: "Culture of C. difficile is of little diagnostic significance because the prevalence of C. difficile in the intestinal tract of healthy piglets is relatively high."
FINANCIAL IMPACT ON FARM'S COST OF PRODUCTION
Level: Moderate: Manageable losses related to endemic (population) or chronic (individual) occurrence
CDAD causes moderate losses in neonatal piglets: (1) Neonatal disease: Affects piglets 1-7 days of age; (2) Variable presentation: "Piglets 1–7 days of age usually present with a history of early-onset scours and rarely with respiratory distress, mild abdominal distension, scrotal edema, or sudden death"; (3) Not epidemic: Disease is sporadic rather than explosive outbreaks; (4) Self-limiting by age: Older pigs develop resistance through microbiota changes; (5) No vaccine available: No commercial immunoprophylaxis available, but disease is manageable through other means. Impact is less severe than C. perfringens type C enteritis.
EFFECT ON DOMESTIC OR EXPORT MARKETS
Level: Negligible: Little or no market disruption when disease occurs on one or more farms
CDAD has no trade implications: (1) Not regulated: Not a reportable disease; (2) Neonatal disease: Affects pre-weaning piglets only; market-age pigs not impacted; (3) No trade restrictions: No country restricts pork trade based on C. difficile status; (4) Ubiquitous organism: C. difficile is found worldwide in human and animal environments.
PATHOGEN'S ABILITY TO DEVELOP AND SPREAD RESISTANCE
Level: Moderate risk: Evidence of development of clinically important resistance to antibacterial or antiviral treatments, or that development of such resistance is likely to occur over time
Antimicrobial resistance is a concern in C. difficile: (1) Human medicine concern: C. difficile ribotype 078 is "among the most commonly isolated strains in cases of multidrug-resistant...CDAD in humans"; (2) Intrinsic resistance: C. difficile has inherent resistance to some antimicrobials; (3) Limited swine data: Specific AMR data for swine isolates not detailed in chapter; (4) Treatment options: "Results of in vitro antimicrobial susceptibility testing suggest that tylosin may be effective" implies susceptibility testing is relevant.
AMR DEVELOPMENT DRIVEN BY DISEASE MANAGEMENT
Level: Minimal risk: Antibacterial or antiviral treatments rarely occur, or are typically limited to short-course individual animal therapy
CDAD in swine is not antibiotic-associated and treatment is limited: (1) Not antibiotic-associated: "Contrary to CDAD in most animal species, antibiotic administration does not seem to be a significant risk factor in pigs"; (2) Limited treatment: Few therapeutic interventions described; (3) Alternative prevention: "Administration of the nontoxigenic strain of C. difficile Z31 reduces the incidence of infection" is a non-antibiotic approach; (4) No widespread treatment protocols: Disease management does not drive significant antimicrobial use.
AVAILABILITY OF EFFECTIVE TREATMENT OPTIONS
Level: Available but with uncertain efficacy: Limited treatments available in US or are only effective in some situations
Limited but some treatment options exist: (1) Tylosin: "Results of in vitro antimicrobial susceptibility testing suggest that tylosin may be effective in treatment of piglets with CDAD"; (2) Competitive exclusion: "Administration of the nontoxigenic strain of C. difficile Z31 reduces the incidence of infection and the intensity of neonatal diarrhea; therefore, this method has been proposed as a preventive measure"; (3) Supportive care: Standard supportive care for diarrheic piglets; (4) Self-limiting: Age-related resistance develops naturally.
AVAILABILITY OF EFFECTIVE VACCINES OR BACTERINS
Level: No availability: Effective vaccines not currently available in the US (or have not been developed)
No commercial vaccines exist: (1) No swine vaccine: "Immunoprophylaxis of CDAD in domestic animals has not been studied widely"; (2) Research precedent: "precedent in other species suggests that immunity will be antitoxic"; "Antibodies against TcdA and TcdB prevent toxin binding in mouse and hamster models"; (3) No commercial development: "in the absence of a commercially available vaccine" alternative strategies like competitive exclusion are proposed; (4) Antitoxic immunity expected: If developed, vaccines would likely target toxins.
FEASIBILITY OF ERADICATING THE DISEASE FROM THE US
Level: Not feasible: Eradication extremely unlikely
Eradication is not feasible due to environmental ubiquity: (1) Ubiquitous organism: C. difficile "can be found in surprisingly large numbers in any environment subject to fecal contamination"; "common in meats and vegetables that have been subjected to fecal contamination"; (2) Spore resistance: "spores of C. difficile are resistant to most common disinfectants"; "Spores are ubiquitous in the environment"; (3) Multiple hosts: Found in "domestic animals (particularly herbivores and swine)" and humans; (4) High colonization rate: "100% of piglets are positive by 3 days postpartum"; (5) Human reservoir: C. difficile is a major human pathogen, making animal-focused eradication meaningless.