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Copyright 2004 Tara K. Harper.  All rights reserved.

TKH Bacteriology Notes:
Botulinus -- updated!

•  Description      •  Mechanism      •  Outbreaks
•  Vector      •  Symptoms      •  Vaccine
     •  Conditions for Growth      •  Odds 'n' Ends
     •  Diagnosis      •  Links
     •  Treatment
     •  Mortality Rates

Science and Literary  Links for Writers
Science and Technical  References for Writers


NOTE:  This file is for information only.  It is not intended for diagnosis.


Botulinus
Also known as:
     - Botulin
     - Botulismotoxin (Botulinus toxin)

Description.  A ubiquitous bacteria found in soil, marine sediments, animal guts, and dung.  Clostridium botulinum is an anaerobic, gram-positive, spore-forming, rod-shaped bacterium that is relatively large.  The spores can be ingested or inhaled, or they can infect an open wound.  However, the bacterium and the spores are not harmful in themselves.  Botulism, a paralytic condition, is caused by the toxins produced by the bacteria, which means that patients are not infected, but intoxicated by botulism.

There are seven strains of botulism, each producing a potent protein neurotoxin.  Types A, B, E, and F cause human botulism.  Type C-alpha causes botulism in domestic and wild waterfowl.  Types C-beta and D cause botulism in cattle.  The seventh type of botulism, strain G, has been isolated from soil samples, but is rare and not currently associated with any known outbreaks of human or animal botulism.

Because botulinum spores exist in soil and marine sediments, the spores can end up in the guts of grazing animals and fish, thus entering the human food chain.  Type A and some of B and F types decompose (digest) proteins in animals, and cause the characteristic smell of rotted food, or putrescence in "bad" meat.  Type E, and some types of B, C, D, and F botulism are not proteolytic (they don't digest animal proteins).  Even when present, those types of botulism may not be detectable by a strong odor.

Clostridium bacteria are heat-resistant and can survive prolonged boiling.  To destroy the actual spores, food must be heated to temperatures of 250 F (120C) or higher, as in a pressure cooker.  Freezing does not destroy the bacteriums or the toxins produced by the bacteriums.

The toxins produced by the spores can be destroyed by heat.  To destroy foodborne toxins, food must be heated to 185 F (85C) or higher for five minutes, or boiled for at least 10 minutes.

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Vector.   Clostridium bacteria are widely distributed throughout the world.  Botulinus occur as both bacterium and spores in soils, in marine sediments, on the surfaces of fruits and vegetables, in the intestinal tracts of mammals and fish, and in the gills and vixcera of shellfish, such as crabs.  Almost any food with a low pH (4.6 or less) can support the growth of the bacterium and the subsequent production of toxin.

Humans--both adults and infants--regularly ingest the spores, but rarely suffer ill effects.  This is because the immune system destroys the spores before they can grow and produce toxin.  Infant botulism is caused by ingestion of the bacteria itself, and not necessarily by ingestion of the toxin.

Almost all outbreaks (90 percent) are associated with improperly preserved home-canned foods.  On some occasions, outbreaks have occurred as a result of improperly prepared commercially canned foods.  Foodborne botulism is usually contracted from contaminated meat (including seafood) and canned vegetables.

Infant botulism is the most common form of botulism.  Researchers have found that, contrary to popular belief, infant botulism is caused by the inhalation of spores (the bacteria itself) along with other microscopic dust particles.  It is not caused primarily by ingesting contaminated honey.  However, the spores have been isolated from 10 percent of both commercial and "natural" honey samples, and at least 5 percent of infant botulism is caused by contaminated honey.

Regardless of the source, children under one year of age have immature immune systems and do not have the necessary proteins in their intestines to destroy the bacterium or spores.  Unchecked, the spores germinate and produce (in the large intestine) the toxins which bind to peripheral motor nerves, causing paralysis and in extreme cases, death.  

Wound botulism is the rarest form of botulism.  It occurs when the bacterium infects a wound (such as a laceration or compound fracture) and produces the toxins in vivo.  The spores germinate locally (in the wound), and the toxins circulate via the bloodstream to reach other parts of the body. The entry wound for the spores may be small and seemingly inconsequential.

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Mechanism.  Botulinum spores are not, in themselves, dangerous.  Only bacteria which are actively metabolizing can produce the botulinus toxin.  It is possible that heat activates the spores to germinate and that this heat also kills other bacteria which would compete with C. botulinum for host resources.  

During growth, C. botulinum produces at least seven different toxins, including neurotoxins, enterotoxins, and haemotoxins, including some of the most potent toxins known.  In rare cases, one strain may produce more than one type of toxin.

Botulinum toxins predominantly affect the peripheral nervous system, specifically:  1) ganglionic synapses, 2) post-ganglionic parasympathetic synapses, and 3) myoneural junctions, the nerve endings where the nerves join muscles and where the toxins block motor nerve terminals.

In the body, neurotransmitters are the chemical messengers used by nerve cells to communicate with each other, and which are used by nerve cells to communicate with muscles.  The botulism toxins cause their characteristic flaccid paralysis by cleaving one of three proteins needed to release the neurotransmitters.  This blocks the release of acetylcholine and the ability of the nerve cells to communicate.

With the toxin blocking the nerve terminals, the nerves cannot signal the muscles to contract.  The patient experiences weakness and paralysis, usually starting with the face, then throat, chest and limbs.  As the diaphragm and chest muscles become involved, breathing becomes difficult, inhibited, or completely paralyzed.  In severe cases, the patient dies from asphyxia.

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Symptoms.  Characteristic symptoms include:  abdominal pain, vomiting, motor disturbances, and visual difficulties.

 •

Foodborne Botulism.  Onset of symptoms usually occurs 12-36 hours after ingestion of the contaminated food, but can take up to 10 days to manifest.  Early symptoms include:  marked lassitude, general weakness, vertigo, and dry mouth.  Subsequent symptoms include:  double-vision, blurred vision, drooping eyelids, progressive difficulty in speaking and swallowing, a nasal or hoarse quality to the voice, difficulty in breathing, weakness of other muscles, abdominal distention, and constipation.  Nausea and vomiting are thought to be local effects of toxin that has been ingested.

Infant Botulism.  Infants with botulism first present with constipation, but parents may not at first notice this symptom.  The infants then become lethargic and floppy, unable to hold their heads up. There may be pooled oral secretions. The infants are unable to form expressions, their crying will become altered until they cannot cry at all, and they will not be able to feed/suck.

Symptoms of infant botulism occur 3 to 30 days after ingestion.  If the symptoms are caught early enough, infants can be treated and supported (tube-feeding, respirators, etc.) through the weeks or months of recovery.  It is possible that up to 5 percent of SIDS (sudden-infant-death syndrome) are actually deaths caused by botulism.  Also, there is a relapse rate of up to 5% with infant botulism.

Wound Botulism.    Gas or suppuration occur in about half the cases of wound botulism.  Symptoms occur 4 to 14 days after exposure to the bacteria.  This is the only type of botulism for which the treatment may include antibiotics.

The CDC recognizes a fourth category for botulism:  indeterminate botulism.  It is possible that this type of botulism is the result of post-surgical changes to the chemistry of the intestinal tract which allows colonization of the intestinal tract by the bacterium.

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Conditions for Germination of Spores in Food.  Certain environmental conditions make it easier for spores to germinate and produce the botulinum toxin.  These conditions include:  

 •

Absence of oxygen, such as a covered storage pot, lidded jar, or other covered container, or a covering substance.  For example, covering food with oil or grease (such as for grilled vegetables) can create the anaerobic environment in which spores can more easily germinate.

A pH environment of 4.6 or higher (a low-acid environment).  Note that a low pH (an acidic environment) does not destroy or inactivate toxins that have already been produced.
 • A salt level lower than 7%.  However, a high salt level may not prevent the bacterium from germinating in whole, salted foods, such as whole, uneviscerated, salted fish.  Refer to the outbreak notes for salted fish.

A sugar content lower than 50%.
 • Warm temperatures, between 40 F and 120 F (4 C to 49 C), such as room temperature.
 • A high moisture content.
 • A lack of competing bacterial flora.

Nitrates, ascorbates, alcohol, refrigeration, and freezing can prevent Clostridium spores from germinating and producing toxins.  However, nitrates, ascorbates, etc. do not destroy the toxins once the toxins have been produced.

Home-canned jams and jellies, because of their high sugar content, do not usually provide an environment in which the spores germinate.  However, home-canned vegetables and meats do not usually have a high sugar content, and can become contaminated during the canning process.

For example, in May, 1973, in the U.S., seven people were treated for food-borne type B botulism after eating contaminated, commercially canned peppers in oil.  In Thailand, between December, 1997, and April, 1998, 19 people contracted type A botulism after eating home-canned bamboo shoots; 3 of those patients died.  Other outbreaks of botulism have been caused by chopped garlic left in oil, baked potatoes wrapped in aluminium foil and left out at room temperature for days, improperly canned green beans, spinach, beets and corn, and so on.

Cheese and other dairy products can also be contaminated with the bacterium.  For example, in 1999, researchers in Rome, Italy, reported testing 1,017 commercially produced mascarpone cheese samples, as well as 260 samples from other dairy products.  Of the mascarpone samples, 331 samples, or 33%, tested positive for botulinum spores.  The 7 samples previously identified as being involved in an outbreak of foodborne botulism were contaminated with type A botulism.  Of the other dairy products, 11 samples tested positive for spores.  The researchers determined that, for mascarpone cheese, at 28 degrees C ( 82 degrees F), the bacterium germinated after 3 days and produced toxins on the fourth day.

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Diagnosis.  Initial diagnosis of patients suffering from botulism can include:  Guillain-Barre syndrome, stroke, intoxication, and myasthenia gravis. Specific tests, such as a brain scan, spinal fuild exam, nerve-conduction test, tensilon test (for myasthenia gravis), and so on can exclude these other conditions.  

The most effective way to diagnose botulism is to demonstrate the botulinum toxin in the patient's serum or stool.

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Treatment.   Antitoxin, administered as soon as possible after diagnosis.  The antitoxin mus be specific to the strain of toxin in the patient.  For example, the toxins of strain B cannot be neutralized by the antitoxin for strain F.

Early administration of antitoxin (made from horse serum) can neutralize toxin that has not yet bound to nerve endings.  However, recovery can take months, and it occurs only when the damaged or affected nerves grow new nerve endings.  In the meantime, patients often require intensive support--respirators, ventilators, tube-feeding, etc.  In severe cases, patients can be weak and feel tired up to a year after onset of symptoms.

Currently, antitoxin is not administered to infants because of the potential for severe side-effects, including anaphylaxis and serum sickness, both of which are life-threatening.

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Mortality Rates.  Between 1910 and 1919, the death rate from botulism was 70 percent in the United States.  Death rates from botulism dropped to 9 percent in the 1980s, and 2 percent in the early 1990s, mainly because of the development of artificial respirators.  Up to 60% of botulism cases can be fatal if left untreated.

The World Health Organization (WHO) reports that the current mortality rate is 5% (type B) to 10% (type A).  Other sources report that, in the U.S., the overall mortality rate is about 7.5%, but the mortality rate among adults 60 years and older is 30%.  The mortality rate for wound botulism is about 10%.  The infant botulism mortality rate is about 1.3%.

One study showed that approximately 5 percent of children whose death was attributed to SIDS had actually died of botulism.

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Outbreaks and History of Infection.  There are 10-30 outbreaks (between 25 and 110 individual cases) of botulism reported in the US each year.  Approximately 75 to 100 individual cases are infant botulism.  In general, 25% of botulism cases are foodborne; 72% are infant botulism, and 3% are wound botulism.  For example, in 2001, in the U.S., there were 97 cases of infant botulism, 39 cases of adult foodborne botulism, and additional cases of wound botulism.

A high percentage of botulism cases (approximately 25 per year) in the U.S. are reported in Alaska, usually from the eating of contaminated marine mammals, such as beaver or beached whale.  Between 1947 and 1974,  there were 21 outbreaks, including 13 deaths, caused by meat prepared in traditional Inuit methods, such as fermenting blubber and flippers in skin pouches and jars at room temperature.  From 1973 to 1998, a total of 236 cases were reported from the eating of raw muktuk (the skin and a pink blubber layer of whales) contaminated with type E botulism, from beached whales.  In January, 2001, an outbreak of 7 cases was traced to fermented beaver tail and paws that had been wrapped in a paper rice sack and stored up to 3 months in the entry of one patient's home.

The incidence of wound botulism in the U.S. has increased recently, especially in California, because of the use of black-tar heroin. The CDC notes that the black tar heroin might be becoming contaminated during the cutting process when adulterants like dirt, boot polish, and other spore-contaminated substances are introduced to the heroin.

Some Recent Outbreaks and Cases:

 •

2002, Poland.  A total of 85 cases of foodborne botulism were registered during 2002, including 5 deaths.  Of the 85 cases, 58 were caused by contaminated meat, including 21 cases from contaminated, home-canned pork, and 17 cases caused by commercially produced sausages.  In 2001, 66 cases were reported, with contaminated meat again being the main cause of botulism.  Contaminated meat products included home-canned pork, homemade sausages, and commercially canned fish.

2002, France.  An outbreak of 9 cases of type B botulism, caused by eating home-canned asparagus.  Six of the nine patients required intubation and respirators.
 • February, 2002, Southern Africa.  First documented outbreak of type A botulism in southern Africa.   Two children (8 and 12 yrs) became acutely paralyzed and died after eating commercially tinned fish in tomato sauce.  It's thought that corrosion (rust) on the can allowed the bacterium to get into and contaminate the food.

August - October, 1999, Morocco.  First botulism epidemic:  11 patients with type B botulism, including one death, after eating mortadella.
 • August, 2001, Texas.  A large outbreak of type A botulism after attendees at at church supper ate contaminated chili.  Fifteen people (40% of the supper attendees) were identified.  The botulism was introduced via a chili bought from a salvage store where investigators found that perishable foods were not well refigerated.
 • January, 1998, Argentina.  First report of a botulism outbreak caused by food stored in heat-shrinked plastic wrap.  An outbreak of 9 cases of type A botulism among bus drivers who ate . matambre, a type of meat roll.  An article in the Journal of American Medical Association (JAMA) reported that the matambre had been cooked below the boiling point of water, at 78 to 80 degrees C, for 4 hours, then sealed in plastic wrap and stored in refrigerators that did not keep the food cold enough to prevent spores from germinating.  Nine of the eleven drivers who ate the matambre required treatment for botulism.

Outbreaks of Botulism in Salted Fish

Although a high salt content will prevent Clostridium from germinating (and producing its toxins), some meat dishes are not necessarily protected simply by adding salt.

Clostridium botulinum has been found in many samples of kapchunka, Faseikh, and other salted, air-dried, uneviscerated whole fish.  Also known as moloha, rybetz, ribbetz, ribeyza or rostov (depending on how it is prepared), the dish is popular in Middle Eastern communities, such as Egypt.

The bacterium has been found in these dishes in spite of salt levels far in excess of 7%, and in spite of proper handling of the fish during processing.  Researchers think that, because the fish are uneviscerated, the guts can provide a relatively low-salt environment that protects the spores and allows them to germinate and produce toxins.

Some sample outbreaks linked to Kapchunka or Faseikh:

 •

June 4, 2004, New Jersey, U.S.  A woman was treated for type A botulism after eating whole, uncut (uneviscerated), salt-cured fish, called Faseikh (feseehk).

1991, Cairo, Egypt.  An major outbreak of type E botulism at least 91 illnesses and 18 deaths that resulted from eating contaminated Faseikh, a whole, uncut (uneviscerated) salt-cured fish.
 • 1981 - 1987, U.S.  Three other outbreaks, including 11 illnesses and 3 deaths, occurred between 1981 and 1987, from eating contaminaed Faseikh.  

October, November 1987, New York City and Israel.   An outbreak of 8 cases of type E botulism, caused by eating ribbetz or kapchunka.

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Vaccine.  A human-derived botulism antitoxin (Botulism Immune Globulin) for types A-E.  There is a separate monovalent vaccine that protects against type F.  Both vaccines have significant shortcomings, including problems with long-term storage.

The June 1, 2004 issue of Biochemistry includes a report from researchers at the U.S. Departmen of Energy's Brookhaven National Laboratory , who have deciphered part of the structure of type E botulism.  This is a significant step toward creating a new, more robust vaccine, or toward creating a drug that would disable the toxins more effectively.

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Odds 'n' Ends
 • How Toxic Is It?  Botulism is one of the most toxic substances by weight known to man.

 •

What's in a Name?  The first accurate description of food-borne botulism symptoms was published around 1820 by a German poet and medical officer Justinus Kerner.  He called the toxin "sausage poison" or "fatty poison."  Eighty years later, in 1895, there was a botulism outbreak after a funeral dinner, in which attendees ate contaminated ham.  This led to Van Ermengen's discovery in 1897 of the pathogen, Clostridium botulinum, that was responsible for the "sausage poison."  The bacterium is called botulism (the Latin word for sausage is "botulus"), not because the bacterium is rod-shaped, but because of its association with poisonings caused by eating badly prepared sausages.
 • Dung in Ancient Egypt.  Botulism was common in ancient Egypt, where physicians used dung as a medicine.

As a Medical Treatment.  Minute doses of type A botulinum toxin are used by doctors to paralyze local muscles and treat a variety of conditions, such as dystonias.  For example, the toxin can be injected into the throat to relax overtightened vocal cords in order to treat vocal disorders.  The toxin is also used to treat teeth grinding, migraines, and muscle spasms of the eyes, face, throat, limbs, and torso.  The toxin (called Botox) works better for small muscles than for large muscles.

The Barbie Doll Cosmetic.  Cosmetic surgeons inject the toxin into local facial muscles to eliminate wrinkles caused by muscle contractions, such as forehead wrinkles, crow's feet, and furrows between the eyebrows.  Botox can cause drooling problems and over time, can atrophy the facial muscles.  Cosmetic doses are usually 1 - 2 % of the dose required to kill a person.

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Links

 •

Todar's Online Textbook of Bacteriology, University of Wisconsin-Madison Department of Bacteriology.  Excellent material on Clostridium bacteria, from Kenneth Todar,  Ph.D.

EMedicine article on botulism.  An overview that includes information about the eight toxins produced (A, B, C1, C2, D, E, F, G) by the bacterium, mechanisms of action, and so on.

A basic, encyclopedic description of the bacterium from Wikipedl.


Copyright 2004 Tara K. Harper

All rights reserved.  It is illegal to reproduce or transmit in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, any part of this copyrighted file without permission in writing from Tara K. Harper.  Permission to download this file for personal use only is hereby granted by Tara K. Harper.


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