Appendix 1

Microbial Intoxications
Introduction

As stated in Chapter 1, the distinction between infectious diseases and microbial intoxications
relates to whether or not the pathogen enters and colonizes the human body. Infectious diseases
involve entry, colonization, and disease production, even when toxins produced by the pathogen
contribute to pathogenesis. Recall that toxins are defined in the book as poisonous substances
produced by microorganisms. Microbial intoxications involve toxins, but they do not involve
entry and colonization by the pathogen.
Microbial intoxications may be caused by bacteria, algae, or fungi. The toxins produced
by bacteria are called bacterial toxins, and the diseases they cause are called bacterial
intoxications or bacterial toxicoses. Toxins produced by algae are referred to as phycotoxins,
and the diseases they cause are called phycotoxicoses. Toxins produced by fungi are called
mycotoxins, and the diseases they cause are called mycotoxicoses.

Bacterial Intoxications

Cyanobacteria

Cyanobacteria are photosynthetic bacteria that live in ponds and lakes. When appropriate
conditions exist (water temperature, nutrients), cyanobacteria will overgrow, creating a water
bloom—a “pond scum” that resembles a thick layer of bluish-green (turquoise) oil paint. Some
cyanobacteria produce toxins, such as neurotoxins (which affect the central nervous system),
hepatotoxins (which affect the liver), and cytotoxins (which affect other types of cells).
Cyanobacterial toxins are harmful to birds, domestic animals, and wild animals that consume
pond or lake water containing these toxins, as well as the minute animals (zooplankton) that live
in the water. In the midwestern United States, thousands of migrating ducks and geese have died
after consuming cyanobacterial toxins. Thus far, no human deaths have been attributed to these
toxins. There is concern, however, that certain cyanobacterial toxins may contribute to the
development of cancer.

Food Poisoning

The term “food poisoning” is broad and may include diseases resulting from the ingestion of
chemical contaminants as well as bacteria, bacterial toxins, phycotoxins, mycotoxins, viruses, or
protozoa. In this section, only diseases resulting from the ingestion of bacteria or the ir toxins are
described. Technically, diseases resulting from the ingestion of toxin-producing bacteria are
called “bacterial infectious diseases” or “bacterial infections,” whereas diseases resulting from
the ingestion of preformed bacterial toxins are called “bacterial intoxications.” The distinction is
based on where the toxin is actually produced—in the body (in vivo) or in the food (in vitro).
Incubation time (the time that elapses between ingestion and onset of symptoms) may be
influenced by a number of factors, including (1) whether toxin-producing bacteria are ingested
(in which case, it will take additional time for the organisms to multiply and produce toxin in
vivo) or preformed toxin is ingested, (2) the number of organisms ingested, and (3) the amount
of preformed toxin that is ingested.

Botulism

Disease characteristics. Botulism is a neuromuscular disease involving a flaccid

type of paralysis. Botulinal toxin may cause nerve damage, visual difficulty, respiratory failure,
flaccid paralysis of voluntary muscles, brain damage, coma, and death within a week if
untreated. Respiratory failure is the usual cause of death. There are actually three types of
botulism, depending on the manner in which the person acquires the disease: (1) classic
foodborne botulism, (2) wound botulism, and (3) infant botulism. Of these, classic foodborne
botulism is truly a microbial intoxication (as defined in this book), involving the ingestion of a
toxin that was produced outside the body. The other two types (wound and infant botulism) are
infectious diseases (again, as defined in this book), involving entry of the pathogen into and
toxin production within the body. Nonetheless, all three types of botulism are described here. A
total of 133 new U.S. cases of botulism were reported to the CDC in 2004. Of these, 16 were
classic foodborne botulism, 87 were infant botulism, and 30 were either wound botulism or
unclassified botulism.

Pathogen. Clostridium botulinum, a spore- forming, anaerobic, Gram-positive,

bacillus that produces botulinal toxin, one of the most potent toxins known to science.

Reservoirs and modes of transmission. Reservoirs include dust, soil, foods

contaminated with dirt, honey, corn syrup, inadequately heated home-canned foods, neutral pH
foods, lightly cured foods. Classic foodborne botulism is the most severe form of food
poisoning, often resulting in death. It follows the ingestion of food (often home-canned fruits or
vegetables) containing botulinal toxin (a potent neurotoxin); thus, in the case of classic
foodborne botulism, the exotoxin is produced in vitro. Infant botulism results from ingestion of
C. botulinum spores (most often in honey), followed by germination of the spores in the infant's
intestinal tract and production of botulinal toxin in vivo. Wound botulism is similar to gas
gangrene, in that clostridial spores enter a wound and germinate, and the toxin is produced in
vivo. Botulism has also occurred among intravenous drug abusers.

Diagnosis. Botulism is diagnosed by demonstrating botulinal toxin in the patient's

serum or gastric aspirate or in the incriminated food, or by culture of C. botulinum from a gastric
aspirate or stool, or a wound culture in the case of wound botulism, or feces in the case of infant
botulism.

Clostri dium perfringens Food Poisoning

Disease characteristics. Clostridium perfringens food poisoning is a

gastrointestinal (GI) toxemia with colic, diarrhea, nausea, rarely vomiting, and fever. It is usually
a mild disease lasting 1 day or less, and is rarely fatal in healthy people. C. perfringens and
Staphylococcus aureus are the two most common causes of food poisoning in the United States.
 Pathogen. C. perfringens, a spore- forming, enterotoxin-producing, anaerobic,
Gram-positive bacillus.

Reservoirs and mode of transmission. Reservoirs include spores in soil and the
GI tract of humans and animals (cattle, swine, poultry, fish). Transmission is via ingestion of
food (usually meat and gravies) contaminated by dirt or feces, kept at moderate temperatures
allowing bacterial growth and exotoxin production.

Diagnosis. C. perfringens food poisoning is diagnosed by demonstration of C.

perfringens in food or the patient’s stool or detection of enterotoxin in the patient’s stool.

Staphylococcal Food Poisoning

Disease characteristics. Staphylococcal food poisoning is a gastroenteritis

intoxication with an abrupt and often violent onset, with severe nausea, cramps, and vomiting,
often with diarrhea and sometimes with below-normal temperature and decreased blood pressure.
It is rarely fatal.

Pathogens. Enterotoxin-producing strains of S. aureus growing in foods.

Reservoirs and modes of transmission. Reservoirs include infected humans

(skin, abscesses, nasal secretions), occasionally cows with infected udders, dogs, and fowl.
Transmission is via ingestion of S. aureus–contaminated foods containing staphylococcal
enterotoxin (a type of heat-stable exotoxin) or foods prepared from contaminated milk or milk
products (e.g., cheese). Typically contaminated foods include custard, cream- filled pastries, salad
dressings, sandwiches, processed meats, and fish.

Diagnosis. In an outbreak, diagnosis is made by recovery of staphylococci from

or detection of enterotoxin in an epidemiologically implicated food. Diagnosis can also be made
by isolation of large numbers of enterotoxin-producing staphylococci from stool or vomitus.
Phage typing can be performed to determine whether the staphylococci recovered from the food
are the same phage type as those isolated from the patient. They are the same phage type if they
are infected by the same bacteriophages.

Algal Intoxications

Although algae rarely cause infectious diseases of humans, many different algae secrete
substances (phycotoxins) that are poisonous to humans, fish, and other animals. In general, the
microbial intoxications caused by phycotoxins are called phycotoxicoses (sing., phycotoxicosis).

Dinoflagellates

Dinoflagellates are microscopic, usually unicellular, flagellated, often photosynthetic algae in the
Division Dinoflagellata. They make up a significant portion of the plankton found in oceans and
lakes and serve as important links in the food chain. There are both heterotrophic and autotrophic
varieties. Dinoflagellates are medically important because of the toxins they produce, which can
cause serious (sometimes fatal) human and animal diseases (Table 1-1).

Table 1-1. Human Diseases Caused by Algal Toxins (Phycotoxins)

Disease Cause

Amnesic shellfish poisoning (one of the Ingestion of shellfish (mussels)

most serious illnesses associated with red containing the toxins of Nitzchia
tide toxins; causes gastrointestinal and pungens, a diatom
neurologic symptoms; can be fatal)

Ciguatera fish poisoning (one of the most Ingestion of fish (usually tropical fish)
frequently reported nonbacterial illnesses containing the toxins of dinoflagellates
associated with eating fish in the United such as Gambierdiscus toxicus,
States and its territories, especially Prorocentrum mexicanum, Ostreopsis
Southern Florida, Puerto Rico, and lenticularis, Coolia monotis,
Hawaii; causes gastrointestinal, Thecadinium sp., and Amphidinium
neurologic, and cardiovascular carterae
symptoms; can cause paralysis; can be
fatal)

Diarrhetic shellfish poisoning (usually a Ingestion of shellfish (mussels, oysters,

mild gastrointestinal disorder) scallops) containing the toxins of
dinoflagellates in the genus Dinophysis

Neurotoxic shellfish poisoning (causes Ingestion of shellfish (oysters, clams)

gastrointestinal and neurologic containing the toxins of the
symptoms; not fatal) dinoflagellate Pytchodiscus brevis; wave
action can produce aerosols which, when
inhaled, can produce respiratory
asthmalike symptoms

Paralytic shellfish poisoning (causes Ingestion of shellfish (mussels, clams,

neurologic symptoms; can cause death) cockles, scallops) containing toxins of
 Alexandrium spp., Gymnodinium
catenatum, Pyrodinium bahamense, and
other dinoflagellates; primarily occurs in
the Pacific Northwest and Alaska

Neurologic and gastrointestinal Ingestion of, or contact with, toxins of

symptoms and skin sores the dinoflagellate Pfiesteria piscicida

Periodically, when conditions (e.g., nutrients, temperature) are ideal, population

explosions of dinoflagellates occur—these are referred to as blooms. Well-publicized examples
are the so-called red tides—harmful algal blooms caused by red dinoflagellates. Red tide toxins
kill fish, whales, dolphins, and manatees. Eating clams, mussels, oysters, or scallops
contaminated by red tide toxins can cause severe (even fatal) illness in humans. Shellfish should
never be harvested during a red tide. As a precaution, some people avoid eating raw shellfish
during months lacking the letter “R” in them (i.e., May, June, July, and August), as red tides are
most likely to occur during those months. In addition, aerosols from red tides can cause
respiratory ailments.

There are also brown tides, which, as a result of the shading they cause and the high algal
biomass, cause adverse effects on the ecosystem. The dinoflagellates associated with brown tides
do not produce toxins, however.

Pfiesteria piscicida

The dinoflagellate that has received the most publicity in recent years is Pfiesteria piscicida. It
not only has killed billions of fish along the eastern seaboard (Chesapeake Bay area and North
Carolina), but its toxins also cause human disease.

Pfiesteria has at least 24 different life cycle stages, including amoeboid, flagellated, and
cyst stages. It emits at least one compound that kills fish and another that opens up the fish’s
skin, creating sores and bleeding, and allowing the organism to feed on the tissue within.

Pfiesteria is also dangerous to humans. Scientists studying the organism and fisherman
have developed sores, headaches, and other neurologic problems from exposure to it. The
clinical features in humans include any of the following signs and symptoms:

• Memory loss
• Confusion/disorientation
• Acute skin burning (on direct contact with water)
• Headaches
• Skin rash
• Eye irritation
• Upper respiratory irritation
• Muscle cramps
• Gastrointestinal complaints (e.g., nausea, vomiting, diarrhea, abdominal cramps)

Fungal Intoxications

Although most fungi do not produce toxins, it has been estimated that mycotoxins are produced
by more than 350 species of fungi. Mycotoxins are complex, organic secondary metabolites that
are harmful to humans and animals (e.g., dogs, horses, pigs, cattle, sheep, turkeys, chickens,
ducks, trout). In general, the microbial intoxications caused by mycotoxins are called
mycotoxicoses (sing., mycotoxicosis). Some fungi produce only a single mycotoxin, but some
may produce more than one. The major actions of mycotoxins are as follows:

• Immunosuppression
• Myelosuppression
• Hepatotoxicity
• Nephrotoxicity
• Neurotoxicity
• Dermatotoxicity
• Mutagenicity
• Teratogenicity
• Carcinogenicity

Until recently, mycotoxins were thought to be acquired solely through ingestion of

mycotoxin-contaminated foods. However, recent evidence suggests that airborne mycotoxins can
cause significant illness in humans and animals. Indoor pollution studies have recently addressed
the role of toxigenic fungi.

The following types of foods have been documented to harbor mycotoxin contaminants:

• Grains
• Seeds
• Vegetables
• Fruits
• Meats
• Cheeses
• Animal feeds and fodder

Certain species of fleshy fungi (mushrooms, toadstools) produce toxins (e.g., phalloidin,
amanitin), but as these fungi are not microorganisms, the intoxications caused by these fungi are
not addressed in this appendix.

Ergot poisoning (also known as ergotism and St. Anthony’s fire) is a human disease,
resulting from the ingestion of grain (wheat, rye) contaminated with the mold, Claviceps
purpurea—a rust fungus. The mycotoxin (ergotamine) causes degeneration of capillaries and
neurologic impairment. Symptoms may include vomiting, diarrhea, thirst, hallucinations, high
fever, convulsions, gangrene of the limbs, and death.

Historical Note. Of Fungi and Witches. There is evidence to suggest that ergotism played a
role in the execution of “witches” in Salem, Massachusetts, in the late 17th century. “Victims” of
these witches may have eaten bread made from rye grain that was contaminated by the mold, C.
purpurea. This mold produces a mycotoxin (ergot), which, when ingested, can produce
symptoms (e.g., convulsions, hallucinations, tingling sensations) similar to those experienced by
the victims in Salem. For an interesting twist on this possibility, you might enjoy reading
Acceptable Risk, a fiction novel by Robin Cook.

Aflatoxins are potent carcinogenic mycotoxins produced by the mold, Aspergillus flavus.
They may be present in cereals or peanut butter made from mold-contaminated grains or peanuts,
respectively. Ingestion of aflatoxins may cause liver damage and hepatic cancer. A type of
esophageal cancer has been associated with Fusarium moniliforme in South Africa. Although
only a few mycotoxins have thus far been proven to cause cancer, the number will probably
grow as additional research is conducted.

A disorder known as “drunken bread eater’s disease” is caused by consumption of bread

made from flour contaminated with a fungus that produces an intoxicating substance.

Mycotoxicoses are more common in domestic animals than humans because animals are
more likely to ingest fungal-contaminated foods. Moist environments, conducive to fungal
growth, are often found in silos and grain storage facilities. The term mycotoxicosis was coined
in 1955 to describe animal illness caused by the ingestion of moldy fodder. Thousands of turkeys
and pigs died in the United Kingdom in 1960 as a result of consumption of animal feeds
prepared from Aspergillus-contaminated ground nuts; most of the animals that survived
developed liver cancer.

Until recently, mycotoxins were thought to be acquired solely through ingestion of mycotoxin-
contaminated foods. However, recent evidence suggests that airborne mycotoxins can cause
significant illness in humans and animals. Indoor pollution studies have recently addressed the
role of toxigenic (toxin-producing) fungi.

Strong evidence suggests that mycotoxins have been obtained for use as biologic warfare
(bw) agents and agents of bioterrorism. For example, at one time, mycotoxins were documented
to be part of Saddam Hussein’s bw armamentarium.