Gas Gangrene,Tetanus,Food Poisoning,Pseudomembranous Colitis
In General
large Gram positive
straight or slightly curved rods with slightly rounded ends
spore bearing
spore do not germinate and growth does not normally proceed unless a suitably low redox potential Eh exists
saprophytes
anaerobic bacilli
some are commensals of the animal and human gut which invade the blood and tissue when host die and initiate the decomposition of the corpse
causes diseases such as gas gangrene,tetanus,botulism and pseudomembranous colitis by producing toxins like neurotoxins which attack the neurous pathways
Clostridium perfringens
a) Description
large Gram-positive bacilli with stubby ends
capsulate
non motile
grown quickly on selective media
can be identified by Nagler reaction which exploits the action of its phospholipase on egg york medium;colonies are surrounded by zones of turbidity and the effect is specifically inhibited if C.perfringens antiserum containing alpha antitoxin is present on the medium
b) Gas gangrene
the disease is characterized by rapidly spreading oedema,myositis,necrosis of tissues,gas production and profound toxaemia occurring as a complication of wound infection
the main source of the organisms is animal and human excreta
the infection usually results from contamination of a wound with soil. However,it may be indirectly derived from dirty clothing,street dust and even the air of an operating theatre if the ventilating system is poorly designed or improperly maintained
i) Pathogenesis of gas gangrene
impairment of the normal blood supply of tissue with a consequent reduction in oxygen tension may allow an anaerobic focus to develop
crushing of tissue and the severing of arteries in accidental injuries;rough handling of tissue and over-zealous clamping during surgery; or shock waves from gunshot injuries may compromise the microcirculation in an extensive area of tissue and prejudice tissue prefusion
the presence of devitalized or dead tissue,blood clot,extravasated fluid,foreign bodies and coincident pyogenic infection are all factors that promote the occurrence of gas gangrene in a wound
the spores of the clostridia and their vegetative bacilli cannot readily initiate infection in healthy tissues because the Eh is too high and the organisms and spores are unable to avoid destruction and clearance by phagcytosis
when clostridal infection has been initiated in a focus of devitalized anaerobic tissue,the organisms multiply and produce a range of toxins and aggressins
they then spread into adjacent vaible tissue,particularly muscle,kill it and render it anaerobic and vulnerable further colonization with the production of more toxins and aggressins
the principal toxin of C.perfringens is the alpha toxin known as phospholipase C (lecithinase)
in pueperal infections or in cases of septic abortion,the organisms may gain access from faeces-contaminated perineal skin or contaminated instruments to necrotic or devitalized tissues in the uterus or adnexa. Here they set up a dangerous and often fulminating pelvic infection,possibly with prompt invasion of the bloodstream
C.perfringens may also participate in peritoneal infections occurring as a result of extension of pathogens from the alimentary or intestinal obstruction or mesenteric thrombosis
c) Laboratory Diagnosis
if there are sloughs of necrotic tissue in the wound,small pieces should be transferred aseptically into a sterile screw-capped bottle and used immediately for microscopical examination and culture
specimens of excudate should be taken from the deeper areas of the wound where the infection seems to be most pronounced
d) Treatment
prompt and adequate surgical attention to the wound is of the utmost importance
sutures are removed,necrotic and devitalized tissue is excised with careful debridement;fascial compartments are incised to release tension;any foreign body is found and removed
antibiotic therapy is started immediately with very high doses
penicillin,metronidazole and an aminoglycoside amy be given in combination
alternatively,clindamycin or a broad-spectrum belta-lactam antibiotic such as cefotaxime or imipenem,may be considered
d) C.perfringens food poisoning
C.perfringens is normally present in considerable numbers in human faeces
these bacteria also occur in animals;thus,meat is often contaminated with their heat-resistant spores
when meat is cooked in bulk,heat penetration is slow and subsequent cooling is slow unless special precautions are taken. The heat-resistant spores may survive and during the cooling period,they will germinate in the anaerobic environment produced by the cooked meat and multiply. THus,anyone who eats this will consume the equivalent of a cooked meat broth culture of the organism. The organisms are protected from the gastric acid by the protein in the meal and pass in alrge numbers into the intestine where they sporulate
enterotoxin released in the gut will cause abdominal cramps about 8-12 h after ingestion,followed by diarrhoea. Fever and vomiting are not typically encountered and symptoms generally subside within a day or two
i) Laboratory Diagnosis
this depends upon the isolation of similar strains of C.perfringens from the faeces of patients and from those at risk who have eaten the suspected food,amd from the food itself. The isolates can be sent to a refernce laboratory for special typing to prove their identity
ii) Prevention
prevent mishandling of foods
Clostridium septicum
a) Description
Gram positive bacilli
shorter,longer and filamentous forms
spores are readily formed
actively motile
numerous peritrichous flagella
it is one of the less exacting anaerobes and grow well at 37 degrees on ordinary media
surface colonies are irregular,transparent and droplet-like,later becoming greyish and opaque
b) Pathogenesis
one of the gas gangrene group of clostridia
also occurs in the human intestine where it is usually harmless
intramuscular injection of cultures in laboratory animals produce a spreading inflammatory oedema,with slight gas formation in the tissues. The organisms invade the blood and the animal dies within a day or two. Smears from the liver show long filamentous forms and citron bodies
Clostridium novyi
Gram Positive bacilli
larger,more pleomorphic and a much more strict anaerobe
it is readily inactivated when its vegetative cell is exposed to air
possesses peritrichous flagella
motility is inhibited in the presence of oxygen
spores are oval,central or subterminal
widely in soil
classified into four types - A,B,C and D - distinguished on the basis of the permutations of the toxins and other soluble antigens they produce
Clostridium sporogenes
Gram positive motile bacillus
widely distributed in nature and also in the intestines of animals
harmless saprophyte
spores are oval,central or subterminal
spores may survive boiling for periods ranging from 15 min up to 6h
Clostridium tetani
a) Description
straight,slender rod with rounded ends
Gram positive,but GRam negative forms are usually encountered in stained smears
the fully developed spores gives the organism the appearance of a drumstick with a large round end
obligate anaerobe
motile and has numerous peritrichous flagella
grows well in cooked meat broth and produces a thin spreading film when grown on enriched blood agar
spores are highly resistant to adverse conditions
spores of some strains resist boiling in water for up to 3h
they may resist dry heat at 160 degrees for 1 h and 5% phenol for 2 weeks or more
iodine (1%) in water is said to kill the spores within a few hours
b) Toxin
produces an oxygen labile haemolysin (tetanolysin) but the organism's neurotoxin (tetanospasmin) is the essential pathogenic product
tetanospasmin is toxic to humans and various animals when injected parenterally,but it is not toxic by the oral route
when tetanus occurs naturally,the tetanus bacilli stay at the site of the initial infection and are not generally invasive,but the toxin diffuses to affect the relevant level of the spinal cord (local tetanus) and then to affect the entire system (generalized tetanus)
the toxin is absorbed from the site of its production in an infective focus and is transmitted to the Central Nervous System (CNS) via motor nerves and apparently specifically by motor fibres. However,some toxin may be delivered from an infective focus via blood to all nerves in the body and the subsequent transmission to the Central Nervous System depends upon uptake through neuromuscular nerve endings and intraaxonal transport
the first signs of human tetanus is to be in the head and neck,attributed to the shorter length of the cranial nerves
the toxin appears to act by interfering with the normal inhibition of motor impulses exercised by the upper motor neurone over the lower,producing an increase in tonus and tonic spasms
c) Occurrence of tetanus bacili
occurs in the intestine of humans and animals
derived primarily from animal faeces and indirectly via soil
especially prevalent in manured soil
d) Pathogenesis
if washed spores are injected into an animal,they fail to germinate and are removed by phagocytosis
germination and outgrowth of tetanus spores depend upon reduced oxygen tension in devitalized tissue and non-viable material in a wound so that the Eh is signficantly lowered
cases of tetanus have been reported in which the infection was apparently assoicated with a superficial abrasion,a contaminated splinter or a minor thorn prick
in some cases,the site of infection is assumed to be in the external auditory meatus;thus otogenic tetanus may be attributable to over-zealous cleansing of the meatus with a small stick
in other patients,the site of infection remains undiscovered,and this is referred to as cryptogenic tetanus
tetanus infection may also occur in or near the uterus in cases of septic abortion
e) Clinical features of tetanus
onset of signs and symptoms is gradual,usually starting with some stiffness and perhaps pain or near a recent wound
pain and stiffness in the neck and back may follow
the period between injury and the first signs is usually about 10-14 days,but there is a considerable range
f) Treatment
the patient remains conscious and requires skilled sedation and constant nursing
if generalized spasms are worrying,the patient is curarized and verntilated mechanically until the toxin that has been taken up has decayed : this may take some weeks
g) Laboratory Diagnosis
simple light microscopy is often unsuccessful;immunoflourescence microscopy with a specific stain is possible but is not generally available
direct culture of unheated material on blood agar incubated anaerobically is often the best method of detection
material from the wound or from a mixed sporing subculture may be heated at various temperatures and for various times to exclude non-sporing bacteria;the heated specimens are then seeded onto solid media and incubated anerobically
tetanus may be produced in mice by subcutaneous injection of an anaerobic culture prepared from wound material
Clostridium botulinum
a) Description
strict anaerobic Gram positive bacillus
motile with peritrichous flagella
spores are oval and subterminal
it is widely distributed saprophyte occurring in soil,vegetables,fruits,leaves,silage,manure,the mud of lakes and sea mud
its optimum growth temperature is about 35 degrees
the widespread occurrence of C.botulinum in nature,its ability to produce a potent neurotoxin in food and resistance of its spores to inactivation combine to make it a formidable pathogen of humans and a range of animals and birds
insufficient heating in the process of preserving foods is an important factor in the causation of botulism and great care must be taken in canning factories to ensure that adequate heating is achieved in all parts of the can contents
b) Toxins of C.botulism
botulinal toxins are among the most poisonous natural substances known
classified into seven types (A-G) with types A,B and E most frequently associated with human disease
c) Human Botulism
botulism is a severe,often fatal,form of food poisoning characterized by pronounced neurotoxic effects
the disease has been caused by a wide range of foods,usually preserved hams,large sausages,home-preserved meats and vegetables,canned products such as fish,liver paste and even hazelnut puree and honey
foods responsible for botulism may not exhibit signs of spoilage
the preformed toxin in the food is absorbed from the intestinal tratc. Although it is protein,it's not inactivated by the intestinal proteolytic enzymes. The toxin primarily affects the cholinergic system and seems to block release of acetylcholine,chiefly at points in the peripheral nervous system
d) Clinical Features
the period between ingestion of the toxin and the appearance of signs and symptoms is usually 1-2 days,but it may be much longer
they may be initial nausea and vomiting
the oculomotor muslces are affected and the patient may have diplopia and drooping eyelids with a squint. THere may be vertigo and blurred vision
there is progressive descending motor loss with flaccid paralysis but no loss of consciousness or sensation,though weakness and sleepiness are often described
the patient is thirsty,with a dry mouth and tongue
there are difficulties in speech amd swallowing,with later problems of breathing and despair
there may be abdominal pain and restlessness
death is due to respiratory or cardiac failure
e) Laboratory Diagnosis
the organism or is toxin may be detected in the suspected food and toxin may be demonstrated in the patient's blood by toxin-antitoxin neutralization test in mice
samples of vomit or faeces may also yield such evidence
f) Treatment
the priorities are - 1) to remove unabsorbed toxin from the stomach and intestinal tract; 2) to neutralize unfixed toxin by giving polyvalent antitoxin and 3) to give relevant intensive care and support
g) Control
home canning of foodstuffs should be avoided and commercial canning must be strictly controlled
acid fruits must be bottled safely in the home with heating at 100 degrees,since low pH is inhibitory to its growth
a prophylactic dose of polyvalent antitoxin should be given intramuscularly to all persons who have eaten food suspected of causing botulism
active immunization should be considered for laboratory staff who might have to handle the organism or who might have to handle specimens containing the organism or its toxin
Clostridium difficile
a) Description
motile Gram positive rod
oval spores
quite commonly in the faeces of neonates,nut is not generally regarded as a normal commensal of adults
produces an enterotxin (toxin A) and a cytotoxin (toxin B)
b) Pathogenesis
this organism has a direct relationship with pseudomembranous colitis
c) Laboratory Diagnosis
can be isolated from the faeces by enrichment and selective culture procedures
toxin can be detected in the patient's faeces by testing extracts against cell monolayers of human embryo fibroblasts or other susceptible cells or by immunological methods such as Enzyme-Linked Immunosorbent Assay (ELISA)
d) Treatment
it is essential to discontinue the antibiotic that is presumed to have precipitated the disease and to suppress the growth and toxin production by gibing oral vancomycin or metronidazole
e) Prevention
clinical awareness is the keynote
if a patient develops unexplained diarrhoea,especially if this is antibiotic-associated,the possibility of C.difficile and pseudomembranous colitis should be borne in mind
if several cases occur in a hospital unit,the psoobility of cross-infection should be considered and the existing antibiotic policy of the unit should be reviewed
