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Microbiology 12 |
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Microbiology 12 |
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NOTE: INFORMATION ON THIS PAGE IS INTENDED FOR EDUCATIONAL USE ONLY. FOR MEDICAL ADVICE YOU SHOULD CONSULT WITH A PHYSICIAN.
Approximately 10 genera of gram positive rods and cocci form endospores, which are dormant, environmentally-resistant survival structures. There are aerobic, facultative and anaerobic genera is this group. Spores germinate into vegetative cells when conditions are favorable. Some important pathogenic spore-formers produce some of the most potent biological exotoxins known.
Two medically-significant genera will be considered here. The genus Clostridium is comprised of strictly anaerobic bacilli that produce terminally-located endospores. The genus Bacillus includes aerobic bacilli that produce central or subterminal endospores.
Table 1. Representative medically important endospore-forming rods
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Bacillus anthracis* |
Anthrax |
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Bacillus cereus |
Food poisoning (intoxication) |
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Clostridium botulinum* |
Foodborne botulism (intoxication); Infant botulism: Wound botulism |
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Clostridium tetani* |
Tetanus |
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Clostridium perfringens |
Food poisoning (intoxication) Gas gangrene, septic abortion |
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Clostridium difficile |
Pseudomembranous colitis |
*These agents are discussed in more detail below. In particular, the role of anthrax and botulinum toxin-biological warfare agents is of immediate concern.
Bacillus anthracis (Gk. Anthrakis = coal)
This spore-forming rod was first isolated as the cause of Anthrax by Robert Koch in 1877. Spores can persist in soil and the environment for decades under a variety of conditions, resisting heat, freezing and ultraviolet radiation from sunlight. Endospores only form under aerobic conditions and are not found in tissues or circulating in the blood. The vegetative cells produce a potent tripartite exotoxin which destroys macrophages.
About Anthrax
Prior to the anthrax cases shortly following the September 11th , 2001 attacks on the World Trade Center in New York, most people were unaware, or at best, vaguely familiar with the disease Anthrax. Detailed accounts and descriptions of the anthrax cases resulting from bioterrorism (as well as other biological weapons) can be found at the Center for Civilian Biodefense Studies at Johns Hopkins University. Countries such as Iraq and the former Soviet Union have been mass producing anthrax for use as a biological weapon for years. During World War II and beyond the U.S. and allies experimented with anthrax as a biological weapon.
The disease is normally a zoonosis, affecting herbivorous, grazing animals such as cattle, goats and sheep. This disease is more common in developing countries where routine vaccination of animals is not carried out. Anthrax can be contracted by animals by eating contaminated flesh or inhaling spores. However, this disease is not contagious and spread animal-to-animal or person-to-person.
Forms of Anthrax
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Cutaneous (>95% cases) |
Spores enter skin lesions and germinate. Usually from contact from contaminated animal hides or wool. Bioterrorist attacks involved handling contaminated letters. |
Over several days a skin lesion appears which may first resemble an insect bite. Vesicles form and the border can be raised and edematous. The center of the lesion becomes black and necrotic and is called an eschar. Lesions are most commonly seen on exposed skin on the arms, face and neck. Bacteria and toxins may spread via the blood and cause meningitis. |
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Inhalational(~5% cases) |
Spores are inhaled. Normally this occurs in people exposed to contaminated animal hides. In the recent bioterrorist attacks, people inhaled aerosolized spores while opening letters. |
This is the most deadly form of the disease if not treated early. The normal incubation period is 1-6 days but spores can persist for up to 60 days. Early symptoms resemble flu . After several days there is increasing respiratory distress. Air spaces fill with fluid, and lymph nodes can obstruct airways. Chest xrays typically show abnormalites. 50% of cases lead to hemorrhagic meninigitis. |
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Oropharygeal and gastrointestinal ( rare-several percent) |
Results from ingesting contaminated, undercooked meat. |
Sore throat and oral ulcers can result along with swelling of lymph nodes in the neck. GI anthrax includes, severe stomach pain, bloody diarrhea and vomiting. |
Treatment and Prevention
Currently ciprofloxacin or doxycycline are drugs or choice for treatment of anthrax. The course is prolonged for 60 days to make sure all organisms are eliminated. People should not stockpile these antibiotics or take them indiscriminately out of fear. Avoid drug resistance! Physicians may change the antibiotic depending upon the susceptibility of the bacteria.
Currently all the available Anthrax vaccine supply is earmarked for the U.S. Military. This decision was made after it was learned Saddam Hussein of Iraq had ordered the mass production of Anthrax biological weapons as warfare agents. You can learn more about the Anthrax vaccine through the Department of Defense. The vaccine does not contain bacteria but is prepared from one of the components of the anthrax toxin called protective antigen which elicits an immune response. The vaccine is given as 6 injections followed by yearly boosters.
Clostridium botulinum (Clostridium =spindle-shaped, L. botulus = sausage)
This spore-former is a common inhabitant of soil and silt and may contaminate fruits, vegetables, meats and sometimes fish. The name botulism was given to this organism because of cases acquired from contaminated sausages. Contaminated food that is to be canned or preserved under anaerobic conditions can create a perfect environment for the germination of botulinum spores. Vegetative cells produce a potent neurotoxin which will cause botulism if ingested in inadequately cooked food. Low-acid, home-canned foods, especially green beans and green peppers, are most commonly implicated. Organisms do not grow well in acidic foods or in the presence of oxygen. Botulinum endospores are the most heat-resistant of any anaerobe and can survive boiling for well over an hour. They can also survive freezing conditions and irradiation.
About botulinum toxin
Only strains of C. botulinum infected with a toxin-encoding phage are able to produce botulinum toxin, The organisms are classified into 8 types according to serologically distinct neurotoxins. Four types cause disease in humans; types A, B and E are usually responsible for most foodborne cases.
Once though to be a classic exotoxin, it is now known that the toxin is only relased by break-down and lysis of the vegetative cell. The toxin is then activated by proteases, possibly including host digestive enzymes. Once ingested the toxin is absorbed in the stomach and becomes fixed in cranial and peripheral nerves. The toxin produces a progressive paralytic disease by binding to acetylcholine (a neurotransmitter) receptors on the motor end plate at the neuromuscular junction. It may also inhibit release of acetylcholine vesicles from the pre-synaptic nerve ending. As a result the muscle fiber cannot contract and is paralyzed.
Interestingly, botulism toxin type A is licensed as a muscle relaxant for therapeutic use in the U.S.A. and is marketed under the name Botox. Botox is only available by prescription and is given by controlled injections. It is given to treat a condition called strabismus (lazy eye) and is used cosmetically to reduce wrinkles and furrowing on foreheads. Migraine sufferers and stroke patients have also benifitted from Botox therapy. The paralysis of the injected Botox is temporary and must be repeated every few months. It is not cheap!
The diseases
Thankfully foodborne botulism is rare and only about 100 cases occur anually in the U.S.A. Symptoms usually occur 1-3 days after eating contaminated food. Nausea and vomiting occur first in about 1/3 of cases and are followed by blurred vision and difficulty swallowing. Motor paralysis usually occurs in a descending pattern involving cranial nerves, limbs and the respiratory muscles. The gag reflex should be checked because, if inhibited by toxin, the patient may aspirate matter into the lungs.
Symptoms of botulism poisoning have also occured in injection drug users in Northern California. Cases appeared in users of black tar heroin who inadvertantly intoduced botulium spores into their tissues during "skin popping."
Infant botulism or "floppy baby syndrome" was first recognized in 1976. About 30-100 cases occur in the U.S.A each year, mostly in California. The disease is associated feeding young infants honey containing botulinum endospores. The spores germinate in the gut and vegetative cells grow in the absence of competing microbia flora. The resultant toxin production causes the infant to become lethargic, limp and has difficulty swallowing.
Wound botulism is extremely rare and is usually only seen in those who have sufferred deep, crushing wounds. Severe tissue damage creates anaerobic conditions for spores to germinate.
What would happen if I inhaled botulinum toxin?
The toxin is among one of the most potent biological agents known and miniscule amounts could potentially cause thousands or millions of deaths raising the concern that this agent could be used as a biological weapon. If aerosolized a single gram of crystallized toxin could kill over a million people. In the 1990's Iraq produced thousands of liters of botulinum toxin and effectively packaged it into warheads and missiles.
Symptoms would occur 1-2 days following inhalation and involve symptoms described for foodborne botulism. Death could occur from respiratory failure as soon as 2-3 days from symptom onset!
Diagnosis
Botulism is diagnosed based on symptoms and history of exposure. Absolute confirmation is made by finding toxin in food or circulating in the patient's serum.
Prevention and Treatment
A polyvaent antitoxin (against types A, B and E) is given as soon as possible after exposure, without waiting for results of a confirmatory test. Other prophylactic measures such as a stomach pump and enema should be instituted. Intesive supportive care, included assisted respiration, should be instituted as soon as symptoms occur. Recovery can take months.
Most cases of foodborne botulism could be prevented by proper cooking of foods as the toxin is inactivated by heat > 85 C. Infant botulism can be prevented by not feeding infants honey in the first year of life.
Clostridium tetani (Gr. tetanos=to stretch)
Like C. botulinum, C. tetani is a common inhabitant of soil and can easily contaminate even minor wounds. Endospores are usually introduced into the skin through deep puncture wounds such as those caused by nails and wood splinters. Once introduced into the tissues the spores germinate under anaerobic conditions into vegetative cells which produce a potent neurotoxin. Other portals of entry include the injection sites of drug abusers, surgical wounds and the umbilical stump of newborns. Sadly, neonatal tetanus remains a significant killer of children in developing countries where spores are introduced into the umbilical stump after cutting it with a dirty razor blade or knife. In addition soil may be smeared over the cut cord.
The disease
In contrast to botulism toxin, which paralyzes nerves in a state of relaxation (flaccid paralysis), tetanus toxin paralyzes nerves in a state of contraction (spastic paralysis). After a 4-10 day incubation period, symptoms of generalized tetanus include widespread muscle stiffness followed by muscle spasms. Classic symptoms include a remarkable posture of an arched back, clenched fists and jaw (lockjaw). Respiratory muscles become paralyzed and most patients die. This is one of few diseases that can be identified based on symptoms alone.
Prevention and treatment
Since the introduction of the tetanus toxoid (inactivated toxin) vaccine in 1933, the disease has become rare in the U.S.A. with less than 100 cases a year. Children are immunized against tetanus beginning with the combined DPT vaccine. Throughout life tetanus boosters are given every 10 years (or following a puncture wound). Nonimmunized persons should receive antitoxin following an exposure, followed by a tetanus vaccine.