Disease associated with Clostridium perfringens (Cp) and other clostridia occur in many different animal species. In swine, three rather common diseases occur. Enterotoxemia associated with C. perfringens type C (CptC) is characterized by variable morbidity and high mortality in neonates or suckling pigs with sudden deaths, bloody diarrhea, or necrotic enteritis. Neonatal diarrhea is also associated with Cp type A (CptA) but with moderate morbidity and lower mortality compared to CptC. Clostridium difficile (Cd) infection of the cecum and colon produces diarrhea with variable morbidity and mortality.
Although most outbreaks of CptC are acute and occur in piglets less than one week old, chronic cases may occur in pigs up to several weeks old. The disease has been reported in many other countries. Incidence in the United States varies greatly and has been high in certain areas. Type C clostridial enteritis also occurs in young lambs, calves, foals and poultry, less often in adult sheep, cattle and goats.
Diarrhea caused by infection with CptA or Cd has emerged in most developed pig production industries around the world and has coincided with the advent of large, intensive swine production systems.
The disease in piglets associated with CptC was reported, reproduced, and researched in the 1960s. Many early reports on CptC enteritis are from species other than swine. Research efforts languished until recent application of gene technologies has allowed further characterization of toxins produced by Clostridium spp. Molecular techniques have also facilitated study and diagnosis of CptA and Cd with particular emphasis on identifying the presence of genes associated with toxin production.
Clostridium perfringens is a large, anaerobic, Gram positive bacillus with both vegetative and sporulated forms. Five toxigenic types (A, B, C, D, E) are distinguished by major toxins they produce (alpha, beta, epsilon, or iota); all types produce alpha toxins. Use of polymerase chain reaction (PCR) technique to detect the genes coding specific toxins has simplified their identification. Type C organisms produce several toxins, especially a necrotizing beta toxin which causes the severe necrotizing enteritis. Clostridium perfringenstype A produces alpha toxin and those pathogenic for swine also produce beta2 toxin. CptA causes much milder enteric insult than CptC.
Virulent strains of Cd are known to produce an enterotoxin (TcdA) and a cytotoxin (TcdB) that are associated with both systemic illness in pigs and localized typhlocolitis and mesocolonic edema. See the table, Clostridial Diseases.
Feces from carrier sows contain pathogenic clostridial organisms and, coupled with contaminated farrowing environment, are the likely source of exposure for piglets. The bacteria and its spores survive in soil and can be carried on shoes, boots or other fomites. Each outbreak renews the supply of clostridia in the farrowing environment available to infect the next litter of susceptible piglets. Although other species of animals have CptC infection, there are few reports of interspecies transmission.
Dose and immunity play a large role in disease occurrence. Immune dams (from exposure and perhaps vaccination) likely provide colostral antitoxin immunity to offspring. Sanitation in farrowing rooms between groups decreases the infectious dose in the environment.
Clostridium perfringens type C organisms are ingested by piglets within a short time of their birth. Conditions that favor proliferation include absence of acid in the stomach and presence of antitrypsin factor. The clostridia proliferate in the small intestine, attach to epithelial cells and produce necrotizing beta toxin that causes necrosis and desquamation of epithelial cells, accompanied by hemorrhage and severe inflammation. Gas is produced and may accumulate in the lumen and/ or wall (intestinal emphysema). Death ensues as a consequence of mucosal necrosis and the systemic effect of toxins on other organs. In older piglets, clostridial colonization may be secondary to other agents of enteritis, most notably coccidiosis, thus contributing to necrotic enteritis. A similar course of events is likely with CptA, with less tissue insult as the expected outcome.
The pathogenesis of Cd has yet to be entirely described. It likely shares features with CptA and CptC but with effects confined to only the cecum and colon. The role of TcdA and TcdB are important as non toxigenic strains of the organism are commonly found in colonic contents in the absence of any clinical signs or lesions. Clostridium difficile enteritis is a common sequelae to long-term oral antibiotic therapy in humans but the disease in swine does not appear to follow this same pattern.
Clinical signs produced by C. perfringens vary depending on infectious dose, virulence, and quantity of antitoxin colostral immunity. Susceptible neonates can become ill in just a few hours after exposure to virulent CptC and may be found dead in as little as 4-8 hours. Sick piglets soon become weak, prostrate and then moribund. Weakened piglets are at high risk of being overlaid by the dam. Piglets with a little more resistance live a few days and may have a bloody diarrhea. Occasionally, piglets may live several weeks, develop a yellow or gray, mucoid diarrhea and remain unthrifty. In acute outbreaks, death can occur even prior to the piglet developing diarrhea. Morbidity is variable but mortality is high, up to l00%, in very susceptible litters.
In uncomplicated CptA infections of both neonatal and weaned pigs, diarrhea is creamy, pasty, or yellow and foamy. Morbidity is high but mortality is generally low. Diarrhea produced by Cd may be indistinguishable from that of CptA or neonatal colibacillosis.
In type C infection there may be blackening of the abdominal skin. The peritoneal and pleural cavities may contain excessive, blood-tinged fluid. Typical acute cases have a dark red, necro-hemorrhagic small intestine. The lesions usually involve the entire small intestine but in some cases may be segmental, usually in the jejunum or ileum. The cecum and colon sometimes are affected. Gas, along with bloody fluid, may be present in the intestinal lumen and wall. Piglets that live a few days may have a necrotic pseudomembrane lining the affected intestine. There may be fibrinous serosal adhesions between loops of affected intestine. Microscopy reveals necrosis with severe suppurative inflammation; organisms in close association with epithelium will also be evident.
Gross lesions are unremarkable with CptA and consist of thin-walled, fluid-filled small intestine. Microscopically, there are often accumulations of neutrophils at villus tips, perhaps with necrosis or sloughing of apical enterocytes. Occasionally, sporulating rods are detected in close association with enterocytes.
Clostridium difficile lesions are confined to the cecum and colon, and include moderate to severe mesocolonic edema, watery colonic contents, and occasionally respiratory symptoms or sudden death. Microscopic erosion of the colonic epithelium with infiltration of mononuclear inflammatory cells is a common finding.
The acute, short course with high morbidity and mortality and typical gross lesions in neonatal piglets are highly suggestive of type CptC enteritis. Identification of a large population of Gram-positive, rod-shaped bacteria in mucosal smears is strongly supportive of the diagnosis. Identification of exceptionally large numbers of C. perfringens in anaerobic cultures from small intestine is helpful. Although seldom necessary, a number of laboratory techniques are available to identify the necrotizing beta toxin in intestinal content from typical cases. Diagnosis can be markedly strengthened by microscopic study of intestinal lesions which are nearly pathognomonic for type C infection. Specimens should be selected from acutely affected pigs early in the course of disease.
Type A infections usually have much milder gross and microscopic lesions, nonbloody diarrhea and lower mortality. Clostridial enteritis must be differentiated from other neonatal diarrheal diseases, including colibacillosis, rotaviral enteritis, transmissible gastroenteritis (TGE) and particularly, coccidiosis.
The PCR technique is now being used in some labs to separate clostridial genotypes C and A. Presence of identified toxic genes correlates closely with production of toxins. An isolate from a typical case may be used to determine the type of infection.
Diagnosis of Cd can be a difficult task but always involves a combination of histopathology, identification of toxin, and culture of the organism.
Immediate passive immunity can be provided for CptC by immune antiserum (antitoxin) given orally or parenterally within two hours of birth. Also, antibiotics effective against clostridia can be given for a few days and may provide some protection.
Considerable protection for piglets (for both CptC and CptA) can be provided by injecting the dams twice with bacterin-toxoid, the first 5-6 weeks and the second 2-3 weeks prior to farrowing. A booster given a few weeks prior to subsequent farrowings is recommended. Where control is less than satisfactory, an autogenous bacterin prepared from an isolate from a typical piglet may be used to vaccinate the sows.
Some benefit may be obtained by feeding antibiotics with anticlostridial activity to sows before farrowing and during lactation. Antimicrobial agents used include bacitracin, tylosin, virginiamycin, lincomycin and others.
Commercial bacterin-toxoids are available for both CptC and CptA.
Programs for consistent control of Cd have not been adequately described. Use of strategic antibiotic therapy in piglets and vaccination of dams with autogenous bacterin-toxoid preparations prior to parturition are being explored.