Clostridium perfringens

style="background:#Template:Taxobox colour;"|Template:Taxobox name
Photomicrograph of gram-positive Clostridium perfringens bacilli.
style="background:#Template:Taxobox colour;" | Scientific classification
Kingdom: Bacteria Phylum: Firmicutes Class: Clostridia Order: Clostridiales Family: Clostridiaceae Genus: Clostridium Species: C. perfringens
Binomial name
Clostridium perfringens Veillon & Zuber 1898 Hauduroy et al. 1937

This page is about microbiologic aspects of the organism(s).  For clinical aspects of the disease, see Gas gangrene.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Clostridium perfringens (formerly known as C. welchii, or Bacillus welchii) is a Gram-positive, rod-shaped, anaerobic, spore-forming bacterium of the genus Clostridium. C. perfringens is everpresent in nature and can be found as a normal component of decaying vegetation, marine sediment, the intestinal tract of humans and other vertebrates, insects, and soil. It has the shortest reported generation time of any organism at 6.3 minutes in thioglycollate medium.

C. perfringens is the third most common cause of food poisoning in the United Kingdom and the United States though it can sometimes be ingested and cause no harm.

Infections due to C. perfringens show evidence of tissue necrosis, bacteremia, emphysematous cholecystitis, and gas gangrene, which is also known as clostridial myonecrosis. The toxin involved in gas gangrene is known as α-toxin, which inserts into the plasma membrane of cells, producing gaps in the membrane that disrupt normal cellular function. C. perfringens can participate in polymicrobial anaerobic infections. Clostridium perfringens is commonly encountered in infections as a component of the normal flora. In this case, its role in disease is minor.

The action of C. perfringens on dead bodies is known to mortuary workers as tissue gas and can be halted only by embalming.

Food poisoning

In the United Kingdom and United States, C. perfringens bacteria are the third most common cause of foodborne illness, with poorly prepared meat and poultry, or food properly prepared but left to stand too long, the main culprits in harboring the bacterium. The clostridium perfringens enterotoxin (CPE) mediating the disease is heat-labile (inactivated at 74 °C (165.2 °F)). It can be detected in contaminated food (if not heated properly), and feces. Incubation time is between six and 24 (commonly 10-12) hours after ingestion of contaminated food.

Since C. perfringens forms spores that can withstand cooking temperatures, if cooked food is let stand for long enough, germination can ensue and infective bacterial colonies develop. Symptoms typically include abdominal cramping, diarrhea; vomiting and fever are usual. The whole course usually resolves within 24 hours. Very rare, fatal cases of clostridial necrotizing enteritis (also known as pigbel) have been known to involve "Type C" strains of the organism, which produce a potently ulcerative β-toxin. This strain is most frequently encountered in Papua New Guinea.

Many cases of C. perfringens food poisoning likely remain subclinical, as antibodies to the toxin are common among the population. This has led to the conclusion that most of the population has experienced food poisoning due to C. perfringens.

Despite its potential dangers, C. perfringens is used as the leavening agent in salt rising bread. The baking process is thought to reduce the bacterial contamination, precluding negative effects.

Infection

Clostridium perfringens is the most common bacterial agent for gas gangrene, which is necrosis, putrefaction of tissues, and gas production. It is caused primarily by Clostridium perfringens alpha toxin. The gases form bubbles in muscle (crepitus) and the characteristic smell in decomposing tissue. After rapid and destructive local spread (which can take only hours), systemic spread of bacteria and bacterial toxins may cause death. This is a problem in major trauma and in military contexts. C. perfringens grows readily on blood agar plate in anaerobic conditions, and often produces a double zone of beta hemolysis.

Research published in 2014 suggested that a strain of C. perfringens might be implicated in multiple sclerosis (MS). Tests in mice found that a toxin made by a rare strain of C. perfringens caused MS-like damage in the brain, and earlier work had identified this strain of C. perfringens in a human with MS. MS patients were found to be ten times more immune-reactive to the epsilon toxin than healthy people.

Diagnosis

C. perfringens can be diagnosed by Nagler's reaction where the suspect organism is cultured on an egg yolk media plate. One side of the plate contains anti-alpha-toxin, while the other side does not. A streak of suspect organism is placed through both sides. An area of turbidity will form around the side that does not have the anti-alpha-toxin, indicating uninhibited lecithinase activity. Other tests/reactions: Catalase: Negative, Spot indole: Positive, Lecithinase: Positive, Lipase: Negative, Litmus Milk: Stormy Fermentation, Reverse CAMP plate: Positive, Gas Liquid Chromatography products: (Acetic, Butyric and Lactic Acids).

Differential diagnosis

Clostridium perfringens infection must be differentiated from other causes of viral, bacterial, and parasitic gastroentritis.

Organism			Age predilection	Travel History	Incubation Size (cell)	Incubation Time	History and Symptoms			Diarrhea type8				Food source	Specific consideration
							Fever	N/V	Cramping Abd Pain	Small Bowel	Large Bowel	Inflammatory	Non-inflammatory
Viral	Rotavirus		<2 y	-	<102	<48 h	+	+	-	+			+	-	Mostly in day cares, most common in winter.
	Norovirus		Any age	-	10 -103	24-48 h	+	+	+	+			+	-	Most common cause of gastroenteritis, abdominal tenderness,
	Adenovirus		<2 y	-	105 -106	8-10 d	+	+	+	+			+	-	No seasonality
	Astrovirus		<5 y	-		72-96 h	+	+	+	+			+	Seafood	Mostly during winter
Bacterial	Escherichia coli	ETEC	Any age	+	108 -1010	24 h	-	+	+	+			+	-	Causes travelers diarrhea, contains heat-labile toxins (LT) and heat-stable toxins (ST)
		EPEC	<1 y	-	10†	6-12 h	-	+	+	+			+	Raw beef and chicken	-
		EIEC	Any ages	-	10†	24 h	+	+	+		+		+	Hamburger meat and unpasteurized milk	Similar to shigellosis, can cause bloody diarrhea
		EHEC	Any ages	-	10	3-4 d	-	+	+		+	+		Undercooked or raw hamburger (ground beef)	Known as E. coli O157:H7, can cause HUS/TTP.
		EAEC	Any ages	+	1010	8-18 h	-	-	+		+		+	-	May cause prolonged or persistent diarrhea in children
	Salmonella sp.		Any ages	+	1	6 to 72 h	+	+	+		+	+		Meats, poultry, eggs, milk and dairy products, fish, shrimp, spices, yeast, coconut, sauces, freshly prepared salad.	Can cause salmonellosis or typhoid fever.
	Shigella sp.		Any ages	-	10 - 200	8-48 h	+	+	+		+	+		Raw foods, for example, lettuce, salads (potato, tuna, shrimp, macaroni, and chicken)	Some strains produce enterotoxin and Shiga toxin similar to those produced by E. coli O157:H7
	Campylobacter sp.		<5 y, 15-29 y	-	104	2-5 d	+	+	+		+	+		Undercooked poultry products, unpasteurized milk and cheeses made from unpasteurized milk, vegetables, seafood and contaminated water.	May cause bacteremia, Guillain-Barré syndrome (GBS), hemolytic uremic syndrome (HUS) and recurrent colitis
	Yersinia enterocolitica		<10 y	-	104 -106	1-11 d	+	+	+		+	+		Meats (pork, beef, lamb, etc.), oysters, fish, crabs, and raw milk.	May cause reactive arthritis; glomerulonephritis; endocarditis; erythema nodosum. can mimic appendicitis and mesenteric lymphadenitis.
	Clostridium perfringens		Any ages		> 106	16 h	-	-	+		+		+	Meats (especially beef and poultry), meat-containing products (e.g., gravies and stews), and Mexican foods.	Can survive high heat,
	Vibrio cholerae		Any ages	-	106-1010	24-48 h	-	+	+	+			+	Seafoods, including molluscan shellfish (oysters, mussels, and clams), crab, lobster, shrimp, squid, and finfish.	Hypotension, tachycardia, decreased skin turgor. Rice-water stools
Parasites	Protozoa	Giardia lamblia	2-5 y	+	1 cyst	1-2 we	-	-	+	+			+	Contaminated water	May cause malabsorption syndrome and severe weight loss
		Entamoeba histolytica	4-11 y	+	<10 cysts	2-4 we	-	+	+		+	+		Contaminated water and raw foods	May cause intestinal amebiasis and amebic liver abscess
		Cryptosporidium parvum	Any ages	-	10-100 oocysts	7-10 d	+	+	+	+			+	Juices and milk	May cause copious diarrhea and dehydration in patients with AIDS especially with 180 > CD4
		Cyclospora cayetanensis	Any ages	+	10-100 oocysts	7-10 d	-	+	+	+			+	Fresh produce, such as raspberries, basil, and several varieties of lettuce.	More common in rainy areas
	Helminths	Trichinella spp	Any ages	-	Two viable larvae (male and female)	1-4 we	-	+	+		+		+	Undercooked meats	More common in hunters or people who eat traditionally uncooked meats
		Taenia spp	Any ages	-	1 larva or egg	2-4 m	-	+	+	+			+	Undercooked beef and pork	Neurocysticercosis: Cysts located in the brain may be asymptomatic or seizures, increased intracranial pressure, headache.
		Diphyllobothrium latum	Any ages	-	1 larva	15 d	-	-	-	+			+	Raw or undercooked fish.	May cause vitamin B12 deficiency

8Small bowel diarrhea: watery, voluminous with less than 5 WBC/high power field

Large bowel diarrhea: Mucousy and/or bloody with less volume and more than 10 WBC/high power field
† It could be as high as 1000 based on patient's immunity system.

The table below summarizes the findings that differentiate inflammatory causes of chronic diarrhea

Cause	History	Laboratory findings	Diagnosis	Treatment
Diverticulitis	Bloody diarrhea Left lower quadrant abdominal pain Abdominal tenderness on physical examination Low grade fever	Leukocytosis Elevated serum amylase and lipase Sterile pyuria on urinalysis	Abdominal CT scan with oral and intravenous (IV) contrast	bowel rest, IV fluid resuscitation, and broad-spectrum antimicrobial therapy which covers anaerobic bacteria and gram-negative rods
Ulcerative colitis	Diarrhea mixed with blood and mucus, of gradual onset. Signs of weight loss Rectal urgency Tenesmus Blood is often noticed on underwear Different degrees of abdominal pain	Anemia Thrombocytosis A high platelet count Elevated ESR (>30mm/hr) Low albumin	Endoscopy	Induction of remission with mesalamine and corticosteroids followed by the administration of sulfasalazine and 6-Mercaptopurine depending on the severity of the disease.
Entamoeba histolytica	Abdominal cramps Diarrhea Passage of 3 - 8 semiformed stools per day Passage of soft stools with mucus and occasional blood Fatigue Intestinal gas (excessive flatus) Rectal pain while having a bowel movement (tenesmus) Unintentional weight loss	cysts shed with the stool	detects ameba DNA in feces	Amebic dysentery Metronidazole 500-750mg three times a day for 5-10 days Tinidazole 2g once a day for 3 days is an alternative to metronidazole Luminal amebicides for E. histolytica in the colon: Paromomycin 500mg three times a day for 10 days Diloxanide furoate 500mg three times a day for 10 days Iodoquinol 650mg three times a day for 20 days For amebic liver abscess: Metronidazole 400mg three times a day for 10 days Tinidazole 2g once a day for 6 days is an alternative to metronidazole Diloxanide furoate 500mg three times a day for 10 days must always be given afterwards.

Food poisoning incidents

On May 7, 2010, 42 residents and 12 staff members at a Louisiana state psychiatric hospital experienced vomiting, abdominal cramps, and diarrhea. Within 24 hours, three patients had died. The outbreak was linked to chicken which was cooked a day prior to being served and was not cooled down according to hospital guidelines. The outbreak affected 31% of the residents of the hospital and 69% of the staff who ate the chicken. It is unknown how many of the affected residents ate the chicken.

In May 2011, a man died after allegedly eating food contaminated with the bacteria on a transatlantic American Airlines flight. The man's wife and daughter are suing American and LSG Sky Chefs, the German company that prepared the inflight food.

In December 2012, a 46-year-old woman died two days after eating a Christmas Day meal at a pub in Hornchurch, Essex, England. She was among about 30 people to fall ill after eating the meal. Samples taken from the victims contained C.perfringens. The hotel manager and the cook were jailed for offences arising from the incident.

In December 2014, 87 year old Bessie Scott died three days after eating a church potluck supper in Nackawic, New Brunswick, Canada. Over 30 other people reported signs of gastrointestinal illness, diarrhea and abdominal pain. The province's acting chief medical officer says Clostridium perfringens is the bacteria that most likely caused the woman’s death.

External links

• Clostridium perfringens genomes and related information at PATRIC, a Bioinformatics Resource Center funded by NIAID
• Pathema-Clostridium Resource