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Clostridial diseases Anthrax. Clostridial diseases. Clostridium spp. Gram positive rods Obligate anaerobes Endospore forming. Clostridium spp. Endospores Resistant to: Heat Disinfectants. Clostridium spp. Soil (found on just about all environmental surfaces)
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Clostridial diseases Anthrax
Clostridial diseases • Clostridium spp. • Gram positive rods • Obligate anaerobes • Endospore forming
Clostridium spp. • Endospores • Resistant to: • Heat • Disinfectants
Clostridium spp. • Soil (found on just about all environmental surfaces) • Fecal matter of humans and animals • Aquatic sediments
Clostridium spp. (obligate anaerobes) • Rapidly killed by highly reactive oxygen radicals • Singlet oxygen • Superoxide free radicals
The Clostridia genus • The clostridia produce a wide variety of extracellular enzymes to degrade large biological molecules in the environment into fermentable components • Hence, the clostridia play an important role in nature in biodegradation and the carbon cycle • In anaerobic clostridial infections, these enzymes play a role in invasion and pathology
Who are the Clostridia’s? • Most of the clostridia are saprophytes but a few are pathogenic for humans • Those that are pathogens have primarily a saprophytic existence in nature and, in a sense, are opportunistic pathogens • Clostridium tetani and Clostridium botulinum produce the most potent biological toxins known to affect humans
Clostridium perfringens • C. perfringens produces a huge array of invasins and exotoxins, causes wound and surgical infections that lead to gas gangrene, in addition to severe uterine infections. • Clostridial hemolysins and extracellular enzymes such as proteases, lipases, collagenase and hyaluronidase, contribute to the invasive process • C. perfringens also produces an enterotoxin and is an important cause of food poisoning. • Usually C. perfringens and C. botulinum is encountered in improperly sterilized (canned) foods in which endospores have germinated
Clostridium difficile • Pseudomembranous colitis in humans is caused by overgrowth ofClostridium difficile in the colon, usually after the normal flora has been disturbed by antimicrobial chemotherapy. • C. difficile produces two toxins: Toxin A is referred to as an enterotoxin because it causes fluid accumulation in the bowel • Toxin B is an extremely lethal (cytopathic) toxin.
Clostridium tetani • Clostridium tetani is the causative agent of tetanus. • The organism is found in soil, especially heavily-manured soils, and in the intestinal tracts and feces of various animals. • Carrier rates in humans vary from 0 to 25%, and the organism is thought to be a transient member of the flora whose presence depends upon ingestion. • The organism produces terminal spores within a swollen sporangium giving it a distinctive drumstick appearance. • Although the bacterium has a typical Gram-positive cell wall, it may stain Gram-negative or Gram-variable, especially in older cells.
Neutralization of oxygen radicals • Superoxide Dismutase (SOD) • Catalase • Clostridium spp. lacks these enzymes
Clostridium spp. • C. tetani • C. botulinum • C. perfringens • C. difficile
Clostridium tetani “Drumstick” appearance
Clostridial diseases • Tetanus • Botulism • Gas gangrene • Foodborne gastroenteritis • Pseudomembrane colitis
TETANUS • Localized infection, caused by a C.tetani toxin • General muscle spasms-due to neurotoxin
TETANUS (cont.) • Trauma (often trivial) • Chronic skin ulcers • Umbilical cord (clay matter ritual in Africa) • Abortion (unsanitary abortions)
TETANUS (cont.) • 300,000/year world wide • 100 cases/year in the USA (24 fatal) • 70% unvaccinated, or incomplete vaccination regime • Mostly 60 years and older
TETANUS (cont.) • Spores in wound • Infection and/or tissue necrosis • Low O2 tension • Spore germination
TETANOSPASMIN • Blocks the muscle relaxation pathway • Death results from spasms of respiratory muscles • Released from dead bacterial cells
TETANOSPASMIN (cont.) • Once it attaches to nerves, therapy is usually ineffective
Advanced case of tetanus Greek tetanos, to stretch
TREATMENT OF TETANUS • Removal of necrotized (death) tissue • Antibiotics • Human immunoglobulins
TETANUS VACCINE Toxin Toxoid Enzyme -S-S- Active Inactive
TETANUS VACCINATION SCHEDULE (CDC) • DTaP vaccine (Diptheria, Tetanus & acellular pertussis) • 2, 4, 6 and 12-18 months • 4-6 years
FOODBORNE BOTULISM • A non-infectious food poisoning • C. botulinum neurotoxin in contaminated food • 34 cases in 1994 (USA)
BOTULIN TOXIN • Most potent of all natural toxins • Approx. 0.001 mg human lethal dose • Causes flaccid paralysis • Death follows cardiac failure
Definitive Diagnosis • only establish with toxin identification: • Isolation of toxigenic cultures and identification of the involved type C or D toxin with the aid of serum neutralization in mice or guinea-pigs. • Toxin detection in clinical samples collected for laboratory analysis (intestinal contents)
Type of tests to ID botulism • tests may include a brain scan, spinal fluid examination, nerve conduction test (electromyography, or EMG), • The most direct way to confirm the diagnosis is to demonstrate the botulinum toxin in the patient's serum or stool by injecting serum or stool into mice and looking for signs of botulism • The bacteria can also be isolated from the stool of persons with foodborne and infant botulism • These tests can be performed at some state health department laboratories and at CDC
BOTULIN TOXIN (cont.) • Home preserves (pH 5 and above) frequent source of botulism • Not formed in pH below 4.7 • Molds may shift pH to above 4.7 • Destroyed by boiling 10 min • Treatment of Botulism NONE
BOTULISM PREVENTION • Preservation of foods at pH below 4.7 • Salt (brine) and sugar • Nitrites in cured foods (remember the nitrites/nitrates in hot dogs, cured ham, processed meats) • Boiling food 10 min
INFANT BOTULISM • Predominant form in the USA • 75-100 cases/year in the USA
INFANT BOTULISM (cont.) • Less than 6 months old children • Associated with ingestion of honey • Honey has endospores in it naturally bees pick up the endospores from the flowers • Immature intestinal microflora of infants leads to infant botulism • children may receive medical attention because of symptoms such as constipation, poor sucking action, a weak cry, and a general, progressive muscle weakness.
Infant botulism detection tests!! • The diagnosis is confirmed by the detection of the organism or its toxin in the infant’s stool • Toxin isolation and identification are accomplished via mouse lethality testing, with typing (type C or D toxin) confirmed by neutralization of toxin by specific sera (antibodies—immunoglobulins)
Where are these endospores commonly found? • More than 90% of reported cases (infant botulism) in the USA come from California, Utah, and southeast Pennsylvania; this is likely a consequence of high concentrations of C. botulinum spores in the soil of these regions
WOUND BOTULISM • C. botulinum develops in grossly contaminated wounds • 19 cases in 1995 • Very common with black tar heroine users/skin popping
Therapeutic use of botulinum toxin blepharospasm and strabismus BOTOX
What is Blepharospasm? Blepharo means "eyelid". Spasm means "uncontrolled muscle contraction". The term blepharospasm can be applied to any abnormal blinking or eyelid tic or twitch resulting from any cause, ranging from dry eyes to Tourette's syndrome to tardive dyskinesia.
What is Strabismus? Strabismus, also known as crossed or turned eye, is the medical term used when the two eyes are not straight. It occurs in approximately 2% to 4% of the population.
GAS GANGRENE • Tissue necrosis (death) from lack of blood supply • Caused by C. perfringens • Neglected wounds (anaerobic conditions) provide a suitable environment for C. perfringens growth
Gas gangrene Clostridium perfringens
GAS GANGRENE (cont.) • Highly lethal if untreated • C. perfringens ferments muscle proteins and carbohydrates producing H2 and CO2 • Predisposing factors: • Dirt in wound • Long delay before wound care • Induced abortion
GAS GANGRENE (cont.) • Predisposing factors: • Arteriosclerosis • Diabetes
Gas gangrene in arm
Bone fracture with gas in surrounding muscular tissue
Gas gangrene in foot
Gas gangrene in foot