Clostridium

Anaerobic spore-forming gram-positive rods:
Four species of clostridium are medical important pathogens:
Clostridium tetani
C.botulinum
C.perfringens
C.difficile

Clostridium tetani:
Important properties:
• It is obligate anaerobe.
• It is gram positive rod.
• Spore-former and bulging end give drum-stick shape.
• It is non-capsulated.
• Motile.
Virulence factors:
• Tetanospasmin(neurotoxin) is major virulence factor.
• Tetanolysin(hemolysin).
Habitat and transmission:
• The organism is found in soil and in intestine of human and animals.
• The portal of entry is wound site when contaminated with the organism or its spore. The organism multiply in tissues that poor supply with blood and oxygen.
Disease and clinical significance:
• Tetanus disease: The organism produce toxin that block release of inhibitory neurotransmitters across synaptic cleft results in stop afferent neuron (failure nervous impulse), and general muscular spasm (contraction) that characterized by severe spasm of voluntary muscles (spastic paralysis).

• After incubation period(3-5 days),In early stages of disease, the jaw muscles are affected as rigid contraction, so that the mouth cannot open ( lockjaw) with dysphagia. Gradually, other voluntary muscles become involved with muscle rigidity, that result in dysurea, constipation, characteristic grimace known as risus sardonicus and arching of back (opisthotonos) due to spasm of strong extensor muscle of back. Sometime convulsion and respiratory muscle spasms(dyspnea) may lead to asphyxia and death.
Lab. Dx:
• Diagnosis depends on the clinical picture of disease.
• Proof of isolation of organism from site of infection.
• No serological tests are available.
Control and therapy:
• Antibiotics treatment: either metronidazole or penicillin G can be given immediately.
• Muscle relaxant and sedatives such as diazepam(valium) should be given to prevent spasms. Artificial ventilation may be necessary.
• Wounds should be cleaned and remove necrotic tissues.
• DTP vaccine is usually given to children and every 10 years. DTP is triple vaccine contain diphtheria toxoid, tetanus toxoid and pertussis (DTP).

Clostridium botulinum :
Important properties:
• Gram positive rod.
• Spore-former.
• It is obligate anaerobe.
• It is non-capsulated .
• It is motile by flagella.
Virulence factors:
• Botulinum toxin(neurotoxin) is major virulence factor.
• Enzymes have important role in pathogenesis.
Source and Transmission:
• The organism is found in microhabitats in colon of humans and animals. While Spores are found in soil.
• Food poisoning results from ingestion of contaminated food especially canned or preserved food without adequate sterilization. Contamination of wounds can be cause wound botulism.
Disease and clinical features:
• Botulism(Food poisoning) is caused by ingestion of toxin-containing food. The toxin is called neurotoxin. After short incubation period (12-36 hr.) is start signs of poisoning with vomiting, thirst(mouth and throat dryness), no fever, difficult in swallowing (dysphagia), difficult in speaking and in breathing , dysurea, constipation , double vision(diplopia),and coma.
The toxin blocks release of acetylcholine(excitatory neurotransmitters) into synaptic gap lead to stop efferent neuron and preventing contraction and causing muscle relaxation that leads to flaccid paralysis. The paralysis of motor muscles which spreading to respiratory and heart muscles and cause death of patient.
• Infant botulism is most common form and associated with ingestion of contaminated honey with spore. Affected infants develop weakness or flaccid paralysis (floppy baby syndrome) and may need respiratory support. These conditions are possibly cause sudden infant death syndrome.

• Wound botulism is result from contaminated wound with organism such as drugs abuse, especially skin-popping with black tar heroin in addicted persons, and tattoo persons.



Control and therapy:
• Botulism antitoxin should be promptly administered if botulism is suspected.
• Antibiotics are generally used for treatment of secondary infection.
• Supportive care such mechanical ventilation and intravenous and nasogastric nutritional support must use.
• Canned food must be sufficient sterilizing. Swollen canned food must be discarded.

Clostridium perfringens:
Important properties:
• Large Gram positive rods.
• Spore-former ,the spore is located in center or sub-terminal of cell.
• It is encapsulated.
• It is non-motile.
Virulence factors:
C. perfringens strains are produce many necrotizing exotoxins. Alpha toxin (lecithinase) that responsible for gas gangrene. Enterotoxin is responsible for food poisoning.
Habitat and transmission:
• The organism is a normal inhabitant of large intestine of humans and animals. The spore is found in soil.
• In food poisoning, the infection occurs after the consumption of contaminated food. While in Gas gangrene is associated with contamination of the wound or traumatized tissues with spore.
Diseases and clinical findings :
1. Gas gangrene(myonecrosis):
• The organism multiply in subcutis tissues and produce lecithinase toxin.
• After incubation period(1-3days). Clinical findings are begins with pain, edema, and cellulitis in wound area. Rapidly progressing necrosis of tissues , fast heartbeat, shock and death. Also the infection is characterized by crepitation (palpable in tissue) due to gas production in tissues, and foul-smell discharge in wounds. Gas gangrene is life-threatening with high mortality rate.
2. Food poisoning(necrotizing enteritis) :
• The organism produces enterotoxin in small intestine(jejenum and ileum).
• After incubation period (8-24 hours)the clinical symptoms which appear as abdominal pain, watery diarrhea with little vomiting and no fever , then recovery without treatment in 12-24 hours.
Lab. Dx:
• The organism can cultured on cooked meat medium(CMM).
• Nagler?s reaction for detection of lecithinase( ?-toxin).
• Serologic tests are not useful.
Control and prevention:
• Gangrenous areas require immediate surgery to excise all affected tissue.
• Wound should be cleansed to remove dead and poorly perfused tissues.
• Antimicrobial treatment is rarely required. Antibiotic choice for treatment of gas gangrene is penicillin-G. Fluid replacement is required in severe food poisoning.
• There are no vaccines.

C. difficile:
Important properties:
• Gram-positive rods.
• Spore-formers and bulging end (drum stick).
• It is non-capsulated.
• Motile.
Virulence factors:
Two types of exotoxin
• Exotoxin-A(enterotoxin) is cause watery diarrhea.
• Exotoxin-B(cytotoxin) is cause damage the colonic mucosa and cause pseudomembrane.
Habitat and transmission:
• The organism is carried in small number of normal flora in GIT.
• The infection is mediated through endogenous spread.
Pathogenesis:
• When antimicrobial treatment(especially wide spectrum) are taken, the antibiotic suppress drug-sensitive members of normal flora of intestine, allowing C. difficile to multiply and produce two exotoxins: A and B.
• Both toxins cause death of enterocytes, and inflammatory response that can lead to pseudomembrane formation in colon.
Disease and Clinical features:
• C.difficile is common causes of antibiotic-associated diarrhea (AAD) about one-fourth of cases. The disease also known as antibiotic-associated pseudomembranous colitis(PMC), and causes toxic megacolon.
• The AAD is life-threatening and fatal disease which characterized by fever, abdominal cramping, necrotizing colitis and diarrhea associated with pseudomembranes (yellow-white plaque, which is best visualized by endoscope), mucus and epithelial cells in stool. The diarrhea may be watery or bloody.
Control:
• Fluid replacement is necessary.
• Treatment with metronidazole or vancomycin administration.
• Toxic megacolon may require surgical resection of colon.