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Fatal Necrotizing Colitis Following a Foodborne Outbreak of Enterotoxigenic Clostridium perfringens Type A Infection

  1. John Bos1,
  2. Lauri Smithee1,
  3. Bruce McClane3,
  4. R.F. Distefano2,
  5. Francisco Uzal4,
  6. J. Glenn Songer5,
  7. Sue Mallonee1, and
  8. James M. Crutcher1
  1. 1 Oklahoma State Department of Health, Oklahoma City
  2. 2 Oklahoma Office of the Chief Medical Examiner, Tulsa
  3. 3 Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  4. 4 California Animal Health and Food Safety Laboratory, University of California at Davis; Davis
  5. 5 Department of Veterinary Science, University of Arizona, Tucson
  1. Reprints or correspondence: John Bos, Acute Disease Service, Oklahoma State Dept. of Health, 1000 NE 10th St., Oklahoma City, OK 73117-1299 (johneb{at}health.state.ok.us).
 
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Abstract

Background Enterotoxigenic Clostridium perfringens type A is the third leading cause of foodborne disease in the United States, resulting annually in an estimated 250,000 cases of a typically mild, self-limiting gastrointestinal illness.

Methods A retrospective cohort study was conducted to determine the cause of a small cluster of cases of gastrointestinal illness, which included cases of severe necrotizing colitis. Participants in the study consisted of residents and staff of a residential care facility for the mentally ill in Oklahoma (n = 20). An inspection of food preparation and food storage areas of the residential care facility was conducted as part of an environmental investigation. The investigation included extensive microbiological and molecular testing of the C. perfringens isolates and tissue specimens collected at autopsy.

Results A total of 7 (3 confirmed and 4 probable) cases of foodborne enterotoxigenic C. perfringens type A were identified (attack rate, 35%) after the consumption of high-risk foods. Three residents developed acute necrotizing colitis; 2 of them died. Each patient with confirmed infection presented with evidence of constipation or fecal impaction. C. perfringens enterotoxin (CPE)-positive C. perfringens type A was cultured on samples from each patient with necrotizing colitis. Although statistical analyses failed to implicate a food source, the isolates carried a chromosomal cpe gene, which supports a foodborne origin.

Conclusions This study confirms that foodborne CPE-positive C. perfringens type A can affect the colon, resulting in potentially fatal necrotizing colitis. Drug-induced constipation and fecal impaction, resulting in prolonged exposure of the colonic mucosal tissue to C. perfringens type A toxins, contributed to the development of necrotizing colitis.

Foodborne transmission of disease in the United States has been estimated to cause 13.6 million cases of illness and up to 2700 deaths annually [1]. Clostridium perfringens isolates are known to cause 2 very different clinical syndromes: the relatively mild gastroenteritis due to infection with type A isolates and the very serious but rare human necrotic enteritis due to infection with type C isolates [2]. Enterotoxigenic C. perfringens type A is the third leading cause of foodborne disease in the United States and is estimated to cause nearly 250,000 cases of illness per year [1]. Among all foodborne pathogen infections, C. perfringens type A infection has one of the lowest hospitalization rates (3 hospitalizations per 1000 cases) and death rates (5 deaths per 10,000 infections) [1].

A small percentage (1%–5%) of C. perfringens type A isolates produces an enterotoxin (CPE) in the small intestine after consumption of a food containing at least 105–107 bacteria [3–6]. The binding of the CPE in the small intestine is typically associated with mild, self-limiting gastrointestinal illness characterized by an incubation period of 8–24 h and acute abdominal pain, diarrhea, and nausea lasting 12–18 h. Fatal cases of C. perfringens foodborne disease are rare and are thought to be limited to elderly, very young, debilitated, or chronically ill persons [4, 6].

On 24 November 2001, a residential care facility (RCF) for the mentally ill in Oklahoma notified the Oklahoma State Department of Health that 2 residents had died and another resident was hospitalized due to a gastrointestinal illness. A large Thanksgiving meal had been consumed 2 days prior to these events. We initiated an investigation to determine the extent and cause of this disease cluster. We report 3 cases of severe necrotizing colitis, including 2 that resulted in death, caused by CPE-positive C. perfringens type A isolates in an outbreak of foodborne illness. To our knowledge, we report the first 3 cases of necrotizing colitis resulting from a foodborne outbreak of CPE-positive C. perfringens type A infection. In addition, the pathology of disease described in this article involves the colon, which previously has not been shown to be involved with a CPE-positive C. perfringens type A etiology.

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Methods

We conducted a retrospective cohort study among residents and staff of the RCF and gathered exposure information, medical histories (including prescription information), acute disease symptomotology, and laboratory information on a standardized data collection instrument. We gathered clinical and laboratory data on hospitalized and deceased individuals from hospital medical records. χ2 Tests, relative risks, and 95% CIs were calculated with EpiInfo software, version 6.04d (Centers for Disease Control and Prevention), in accordance with the methods of Mehta et al. [7]. Stool specimens were obtained when available. A standard autopsy and toxicology analysis was performed for each fatal case by the Office of the Chief Medical Examiner, and tissue specimens were obtained.

A licensed environmental specialist conducted an environmental investigation, which included inspection of the RCF's food preparation and food storage areas. The RCF food handler was interviewed to obtain a thorough food preparation history focused on the food items prepared for the large Thanksgiving meal.

A confirmed case was defined as a positive result of laboratory culture for CPE-positive C. perfringens type A in samples from a person who was a resident of the RCF who had an onset of symptoms from 22 November to 24 November 2001; a probable case was defined as vomiting or diarrhea (⩾3 loose stools in a 24-h period) experienced by a resident of the RCF who had a reported onset of symptoms from 22 November to 24 November 2001.

Fecal specimens from patients were submitted for anaerobic culture and identification with the use of the RapID ANA II System (Innovative Diagnostic Systems) in accordance with the instructions of the manufacturer. Isolates confirmed as C. perfringens were tested for CPE with the use of a reverse passive latex agglutination (PET-RPLA) CPE toxin detection kit (Oxoid) in accordance with the instructions of the manufacturer. The ability of the isolates to express the cpe gene was then further confirmed using Western blot analysis, as described elsewhere [8]. C. perfringens toxin type was assigned using a multiplex PCR assay [9]. A duplex PCR assay was used to determine whether the cpe genes in these isolates were either chromosomal or plasmid-borne [10]. The clonality of isolates from cases was examined by an unpublished PCR procedure that tests for the presence and length of 4 short repetitive sequences, or variable number of tandem repeats (VNTRs).

Sections of affected colon collected at autopsy were cut and were hematoxylin and eosin-stained and Gram-stained for histological analysis. The tissue sections were then tested for the presence of CPE by immunohistochemical staining. From the colons of 2 patients, 4-µm-thick paraffin sections were processed with an indirect immunoperoxidase technique for CPE, by use of the Dako EnVision kit (Dako), in accordance with the manufacturer's instructions, and by use of a monoclonal antibody against CPE. The colon of a rabbit inoculated experimentally with CPE was used as a positive control. The colon of a rabbit inoculated with phosphate-buffered saline (pH, 7.2) and the colon from a human were used as negative controls. The following case reports include information regarding each of the confirmed, outbreak-associated cases of CPE-positive C. perfringens type A infection.

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Case Reports

Patient 1

A 39-year-old white woman with a history of paranoid schizophrenia, depression, hypothyroidism, hypertension, and chronic constipation experienced an acute onset of diarrhea, nausea, and vomiting on 22 November 2001. The next morning, she continued to experience diarrhea and was found incontinent, with large amounts of liquid stool. Her condition rapidly deteriorated, and, ∼17 h after the onset of symptoms, the patient became unresponsive, went into cardiopulmonary arrest, and was pronounced dead on arrival at the hospital.

At autopsy, the small and large bowels were notably distended by copious gray-tan to dark-brown fluid and some semisolid fecal material. There was no perforation or peritonitis. Within the large bowel, the mucosa of an ∼30.5-cm-long segment of the transverse colon was necrotic. This segment was distinctly black in color, in contrast to the remainder of the colonic mucosa, which was grossly unaffected. On histological examination, the colon showed severe multifocal to coalescent acute mucosal necrosis that involved the superficial epithelium and lamina propria, with complete loss of the colonic epithelium. There was also severe diffuse hemorrhage and inflammatory infiltrate consisting of mainly neutrophils and a few lymphocytes, plasma cells, and macrophages. The inflammation involved all layers of the colon, including the serosa. A large number of gram-positive rods with rounded ends were present on the surface of the mucosa and were mixed with sloughed epithelial cells and inflammatory exudates in the intestinal lumen and deep in the mucosa. Unaffected areas of the small and large bowels were essentially unremarkable on microscopic evaluation. Immunohistochemical staining of colonic tissue specific to CPE was not observed, perhaps because of the complete loss of the colonic epithelium.

The patient had been a resident of the RCF for >2 years. Her daily multidrug treatment regimen consisted of topiramate, ranitidine, benztropine mesylate, clozapine, sertraline, oxcarbazepine, furosemide, hydroxyzine hydrochloride, diphenhydramine hydrochloride, and trazodone.

Patient 2

A 58-year-old black man with a history of schizophrenia, hypertension, emphysema, and chronic constipation had an acute onset of abdominal pain, diarrhea, and vomiting midmorning on 23 November 2001. His condition was treated at a local hospital, and he was released with an order to increase oral fluid intake. Two hours later, he was disoriented and complained of symptoms consistent with acute gastrointestinal illness. He was found to be incontinent, with copious amounts of liquid stool and a large mass of hard feces, and he returned to the hospital. His vital signs were normal, and his abdomen was soft and without tenderness and had no evidence of obstruction. The results of standard laboratory tests, including a complete blood cell count with differential and basic metabolic profile, were unremarkable. His condition was treated intravenously with 1 L of normal saline and 12.5 mg of promethazine hydrochloride, and he was released. The patient continued to experience diarrhea and complained of left-side abdominal pain. At 7 h after his return from the hospital and ∼24 h after the onset of illness, the patient was found to have no pulse and was pronounced dead.

At autopsy, necrosis was observed on the colonic mucosa, beginning with the splenic flexure and including the descending colon and portions of sigmoid, with relative discrete delineation from unaffected areas (figure 1). The left half of the transverse colon and the descending colon contained a moderate amount of watery, turbid, yellow-brown fluid. The small bowel and segments of the large bowel consisting of the ascending colon and the right half of the transverse colon were unremarkable. On histological analysis, the finding of severe multifocal to coalescent acute mucosal necrosis was consistent with the findings for case 1. However, a few areas of remaining colonic epithelium were observed. The inflammation involved all layers of the colon, including the serosa. A large number of gram-positive rods with rounded ends were present on the surface of the mucosa and were mixed with sloughed epithelial cells and inflammatory exudate in the intestinal lumen and deep in the mucosa. Immunostaining specific to CPE was observed as clumps on the surface of the mucosa and included most of the rods seen in the mucosa.

Figure 1
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Figure 1

Colon with necrosis, from patient 2

Figure 2
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Figure 2

Genotyping of Clostridium perfringens isolates cultured from stool samples for each confirmed case of infection. For patient 3, multiple isolates obtained from specimens collected at various facilities were submitted for genotyping.

Figure 3
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Figure 3

Subgenotyping of Clostridium perfringens isolates cultured for each confirmed case of infection. For patient 3, multiple isolates obtained from specimens collected at various facilities were submitted for subgenotyping.

The patient had been a resident of the RCF for 5 years. His daily multidrug treatment regimen consisted of trazodone, risperidone, olanzapine, carbamazepine, citalopram hydrobromide, benztropine mesylate, lorazepam, oxybutynin chloride, desmopressin acetate, hydrochlorothiazide, and ibuprophen.

Patient 3

A 59-year-old black man with a history of schizophrenia and chronic constipation complained of gastrointestinal illness consisting of nausea, vomiting, and diarrhea midmorning on 23 November 2001. He defecated a large mass of hard feces and copious amounts of loose stool. He was transported to the hospital, where a complete blood cell count with differential and basic metabolic profiles revealed a WBC count of 12.6 ×103 cells/µL, with 83% neutrophils and 4.6% lymphocytes, a blood urea nitrogen level of 22 mg/dL, and a creatinine level of 1.8 mg/dL. His condition was treated with 1 L of normal saline and diphenoxylate/atropine sulfate for the gastrointestinal symptoms and dehydration, and he was then released from the hospital. Within 14 h of his release, he collapsed and was again transported to the local hospital, evaluated, and released. Approximately 24 h later, he walked out of his RCF room and collapsed again.

The patient was repeatedly hospitalized due to complaints of gastrointestinal illness and then released. On physical examination, his abdomen was soft, with slight tenderness and distention. Subsequent complete blood cell count and metabolic profiles remained within normal limits. A flexible sigmoidoscopy performed on 28 November 2001 indicated severe pseudomembranous colitis and possible ischemic bowel.

The patient was a resident of the RCF for 5 years. His daily multidrug treatment regimen consisted of fluoxetine hydrochloride, benztropine mesylate, vitamin E, olanzapine, and lorazepam.

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Results

All residents and staff of the RCF consumed a large Thanksgiving meal at ∼12:00 P.M. on 22 November 2001. The food items served included turkey, ham, sweet potatoes, dressing, and turkey gravy. Improper food-handling practices were identified in the storage and preparation of the large number of turkeys served to the residents and staff of the RCF.

Of the 26 residents and staff of the RCF, 20 provided exposure and acute illness histories. Seven cases (3 confirmed and 4 probable) of foodborne CPE-positive C. perfringens type A infection were identified (attack rate, 35%); no staff members developed the illness. The median age at onset was 48 years (range, 30–59 years); 4 (57%) of the 7 infected patients were female. The onset of illness among patients ranged from 22 November through 23 November 2001. Symptoms associated with illness included diarrhea (100% of infection persons), abdominal cramps (100%), vomiting (71%), and fever (14%). The median incubation period for confirmed cases was 18 h (range, 10–22 h) after the consumption of the Thanksgiving meal. Statistical analysis failed to implicate a food source (table 1), and no food items from the Thanksgiving meal were available for bacterial culture. Three (43%) of the patients developed severe bowel necrosis, which resulted in 2 deaths.

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Table 1

Frequency of exposure to foods among residents and staff of the Oklahoma residential care facility for the mentally ill in November 2001.

C. perfringens was cultured from each patient presenting with necrotizing colitis. A Western blot analysis established that isolates from each confirmed case were capable of producing CPE, validating the initial positive identification of CPE expression by PET-RPLA. Each isolate had a positive result of PCR for the cpe gene and the alpha toxin (p/c) gene but not for the β, ated, if not identical. No fecal specimens from probable cases were provided for laboratory testing.

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Discussion

The 3 cases of necrotizing colitis resulting from a foodborne outbreak of CPE-positive C. perfringens type A are remarkable, because CPE has not previously been shown to affect the human colon. The 3 cases presented here differ from the fatal cases attributed to enterotoxigenic (or CPE-positive) C. perfringens type A in the literature, which are typically due to dehydration in elderly, very young, debilitated, or chronically ill persons [4, 6]. Despite their mental illness, the patients reported in the current study were not otherwise physically debilitated or immunocompromised.

We believe that constipation and fecal impaction may have been risk factors for developing necrotizing colitis after the ingestion of contaminated food. Constipation likely resulted from the anticholinergic effects of psychiatric medications. The distinct delineation of the necrotic and unaffected mucosal tissues seen on examination of the colon is thought to be the result of a fecal impaction preventing the expulsion of CPE through the usual protective effects of diarrhea; thus, the prolonged exposure of the tissue to the CPE (and perhaps to other toxins of C. perfringens type A) resulted in the severe necrotic process. The cause of death in each of the fatal cases was determined to be severe colon necrosis. Although disease due to the release of CPE after foodborne transmission of CPE-positive C. perfringens is typically mild, animal experiments provide support for the potency of CPE in a closed gastrointestinal tract [11].

C. perfringens type A is a ubiquitous organism that is part of the normal fecal flora of humans [3, 4]; therefore, a positive culture result does not confirm a C. perfringens type A etiology of disease. Considerable epidemiologic evidence implicates CPE as the virulence factor responsible for most (if not all) of the diarrheal and cramping symptoms associated with C. perfringens type A foodborne disease [12]. CPE detection in samples from the 3 patients provides definitive evidence for the confirmation of a CPE-positive C. perfringens type A etiology [13–15]. Additionally, immunostaining specific to CPE at the site of necrosis was observed for the patient with remaining enterocytes, which strongly suggests that this toxin was involved in the pathogenesis of the condition.

CPE-positive C. perfringens type A isolates are classically associated with foodborne disease [1, 4–6, 16]. However, during the past 15 years, CPE-positive C. perfringens type A isolates have become linked to several cases of nonfoodborne gastrointestinal disease, [17–21] including up to 5%–20% of all antibiotic-associated diarrhea [22]. It is now evident that the cpe gene typically has a chromosomal location in CPE-positive C. perfringens type A transmitted through food [21, 23, 24] but is plasmid-borne in CPE-positive C. perfringens type A not transmitted through food [17, 21]. Disease from nonfoodborne C. perfringens type A occurs almost exclusively in elderly persons and is typically more severe, with a longer duration of illness [19, 25].

We believe that this outbreak of CPE-positive C. perfringens type A-associated disease was foodborne. The acute onset of illness among residents of the same RCF suggests a point-source foodborne disease outbreak and was consistent with the observed incubation period after the consumption of turkey, a common food vehicle for CPE-positive C. perfringens [15, 26, 27]. In addition, the isolates were found to carry the cpe gene on the chromosome and not on the plasmid, which provides additional support that the source of the disease was a food product [10]. C. perfringens foodborne isolates with the cpe gene carried on the chromosome are more heat resistant than are those with the gene carried on the plasmid; thus, their survival is favored in inadequately cooked foods.

Conducting an epidemiologic investigation among a cohort of persons who are independent in feeding and toileting yet who have difficulty communicating exposure and illness history presented several limitations. Six residents unable to answer questions about symptoms and food history were excluded from the analysis, which limited additional case findings and reduced the sample size for analysis of exposure variables. In addition, there were no leftover food items available for testing. These limitations prevented us from identifying a specific food source.

These case reports demonstrate the potential seriousness of C. perfringens foodborne disease, particularly in a medicated population at risk of chronic constipation. The bowel health of patients receiving medications that may cause constipation should be closely monitored, and stool softeners should be prescribed as needed. It is likely that most outbreaks of C. perfringens foodborne disease occur in institutions and food service facilities that cook large amounts of food well in advance of serving [4]. Outbreaks of foodborne disease, including those resulting from CPE-positive C. perfringens type A, are preventable through the use of safe food-handling practices. Food handlers in these facilities should be trained in food safety. In addition, patients presenting with necrotizing colitis of unknown cause should be evaluated for a CPE-positive C. perfringens type A etiology of disease.

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Acknowledgments

We thank Mike McDermott (Oklahoma State Department of Health), Qiyi Wen (Department of Molecular Genetics and Biochemistry, University of Pittsburgh), Youhanna Sawires (University of Arizona), and J. Hurley and M. Rhea (California Animal Health and Food Safety Laboratory System, University of California at Davis), for their expertise in laboratory testing for CPE-positive C. perfringens type A.

Financial support. A portion of the laboratory research was supported by grants AI019844-21 and AI056177-02 from the National Institute of Allergy and Infectious Diseases and by grant 2001-0517 from the Ensuring Food Safety Program of the US Department of Agriculture.

Potential conflicts of interest. All authors: no conflicts.

  • Received November 8, 2004.
  • Accepted January 24, 2005.
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References

  1. ↵
    1. Mead PS,
    2. Slutsker L,
    3. Dietz V,
    4. et al
    . Food-related illness and death in the United States. Emerg Infect Dis 1999;5:607-25.
    MedlineWeb of Science
  2. ↵
    1. Granum PE
    . Clostridium perfringens toxins involved in food poisoning. Int J Food Microbiol 1990;10:101-12.
    CrossRefMedlineWeb of Science
  3. ↵
    1. Jolik WK,
    2. Willett HP,
    3. Amos DB,
    4. Wilfert CM
    1. Hill GB,
    2. Willett HP
    . Clostridium. In: Jolik WK, Willett HP, Amos DB, Wilfert CM, editors. Zinsser microbiology. 20th ed. East Norwalk, CT: Appleton and Lang; 1992. p. 636-56.
  4. ↵
    1. Brynestad S,
    2. Granum PE
    . Clostridium perfringens and foodborne infections. Int J Food Microbiol 2002;74:195-202.
    CrossRefMedlineWeb of Science
    1. Mandell GL,
    2. Bennett JE,
    3. Dolin R
    1. Lorber B
    . Gas gangrene and other Clostridium-associated diseases. In: Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas, and Bennett's principles and practice of infectious diseases. 5th ed. Philadelphia: Churchill Livingstone; 2000. p. 2549-61.
  6. ↵
    1. Shandera WX,
    2. Tacket CO,
    3. Blake PA
    . Food poisoning due to Clostridium perfringens in the United States. J Infect Dis 1983;147:167-9.
    FREE Full Text
  7. ↵
    1. Mehta CR,
    2. Patel NR,
    3. Gray R
    . Computing exact confidence interval for the common odds ratio in several 2 × 2 contingency tables. J Am Stat Assoc 1985;78:969-73.
    CrossRef
  8. ↵
    1. Sarker MR,
    2. Shivers RP,
    3. Sparks SG,
    4. et al
    . Comparative experiments to examine the effects of heating on vegetative cells and spores of Clostridium perfringens isolates carrying plasmid versus chromosomal enterotoxin genes. Appl Environ Microbiol 2000;66:3234-40.
    Abstract/FREE Full Text
  9. ↵
    1. Garmory HS,
    2. Chanter N,
    3. French NP,
    4. et al
    . Occurrence of Clostridium perfringens b2-toxin amongst animals determined using genotyping and subtyping PCR assays. Epidemiol Infect 2000;124:61-7.
    CrossRefMedline
  10. ↵
    1. Wen Q,
    2. Miyamoto K,
    3. McClane BA
    . Development of a duplex PCR genotyping assay for distinguishing Clostridium perfringens type A isolates carrying chromosomal enterotoxin (cpe) genes from those carrying plasmid-borne enterotoxin (cpe) genes. J Clin Microbiol 2003;41:1494-8.
    Abstract/FREE Full Text
  11. ↵
    1. Sarker M,
    2. Carman R,
    3. McClane B
    . Inactivation of the gene (cpe) encoding Clostridium perfringens enterotoxin eliminates the ability of two cpe-positive C. perfringens type A human gastrointestinal disease isolates to affect rabbit ileal loops. Mol Microbiol 1999;33:946-58.
    CrossRefMedlineWeb of Science
  12. ↵
    1. Doyle MP,
    2. Beuchat LR,
    3. Montville TJ
    1. McClane B
    . Clostridium perfringens. In: Doyle MP, Beuchat LR, Montville TJ, editors. Food microbiology: fundamentals and frontiers. 2nd ed. Washington, DC: ASM Press; 2001. p. 351-72.
  13. ↵
    1. Jackson S,
    2. Yip-Chuck D,
    3. Clark J,
    4. et al
    . Diagnostic importance of Clostridium perfringens enterotoxin analysis in recurring enteritis among elderly, chronic care psychiatric patients. J Clin Microbiol 1986;23:748-51.
    Abstract/FREE Full Text
    1. Mpamugo O,
    2. Donavan T,
    3. Brett MM
    . Enterotoxigenic Clostridium perfringens as a cause of sporadic cases of diarrhoea. J Med Microbiol 1995;43:442-5.
    Abstract/FREE Full Text
  15. ↵
    1. Birkhead G,
    2. Vogt R,
    3. Heun E,
    4. et al
    . Characterization of an outbreak of Clostridium perfringens food poisoning by quantitative fecal culture and fecal enterotoxin measurement. J Clin Microbiol 1988;26:471-4.
    Abstract/FREE Full Text
  16. ↵
    1. Loewenstein MS
    . Epidemiology of Clostridium perfringens food poisoning. N Engl J Med 1972;286:1026-8.
    CrossRefMedlineWeb of Science
  17. ↵
    1. Sparks SG,
    2. Carman RJ,
    3. Mahfuzur RS,
    4. McClane BA
    . Genotyping of enterotoxigenic Clostridium perfringens fecal isolates associated with antibiotic-associated diarrhea and food poisoning in North America. J Clin Microbiol 2001;39:883-8.
    Abstract/FREE Full Text
    1. Borriello SP,
    2. Barclay FE,
    3. Welch AR,
    4. et al
    . Epidemiology of diarrhea caused by enterotoxigenic Clostridium perfringens. J Med Microbiol 1985;20:363-72.
    Abstract/FREE Full Text
  19. ↵
    1. Brett MM,
    2. Rodhouse JC,
    3. Donovan TJ,
    4. et al
    . Detection of Clostridium perfringens and its enterotoxin in cases of sporadic diarrhea. J Clin Pathol 1992;45:609-11.
    Abstract/FREE Full Text
    1. Collie RE,
    2. Kokai-Kun JF,
    3. McClane BA
    . Phenotypic characterization of enterotoxigenic Clostridium perfringens isolates from non-foodborne human gastrointestinal diseases. Anaerobe 1998;4:69-79.
    CrossRefMedlineWeb of Science
  21. ↵
    1. Collie RE,
    2. McClane BA
    . Evidence that the enterotoxin gene can be episomal in Clostridium perfringens isolates associated with nonfoodborne human gastrointestinal diseases. J Clin Microbiol 1998;36:30-6.
    Abstract/FREE Full Text
  22. ↵
    1. Carman RJ
    . Clostridium perfringens in spontaneous and antibiotic-associated diarrhoea of man and other animals. Rev Med Microbiol 1997;8(Suppl 1):S43-5.
  23. ↵
    1. Cornillot EB,
    2. Saint-Joanis B,
    3. Daube G,
    4. et al
    . The enterotoxigenic gene (cpe) of Clostridium perfringens can be chromosomal or plasmid-borne. Mol Microbiol 1995;15:639-47.
    CrossRefMedlineWeb of Science
  24. ↵
    1. Katayama SI,
    2. Dupuy B,
    3. Daube B,
    4. et al
    . Genome mapping of Clostridium perfringens stains with I-Ceu I shows many virulence genes to be plasmid-borne. Mol Gen Genet 1996;251:720-6.
    MedlineWeb of Science
  25. ↵
    1. Borriello SP
    . Clostridial diseases of the gut. Clin Infect Dis 1995;20(Suppl 2):S242-50.
    CrossRefMedlineWeb of Science
  26. ↵
    1. Parikh AJ,
    2. Jay MT,
    3. Kassam D,
    4. et al
    . Clostridium perfringens outbreak at a juvenile detention facility linked to a Thanksgiving holiday meal. West J Med 1997;166:417-9.
    MedlineWeb of Science
  27. ↵
    1. Olsen SJ,
    2. MacKinnon LC,
    3. Goulding JS,
    4. Bean NH,
    5. Slutsker L
    . Surveillance for foodborne disease outbreaks—United States, 1993–1997. MMWR Morb Mortal Wkly Rep 2000;49(SS-01):1-51.
    Medline
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  1. Clin Infect Dis. (2005) 40 (10): e78-e83. doi: 10.1086/429829
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