LEGAL
NOTICE: All information on these pages is your choice
as to response. Steve
Van Nattan is not any kind of an authority
on anything for anyone.
ANOTHER
MORE "FIELD" ORIENTED DISCUSSION
OF TOXINS
Includes "Yellow Rain" This discussion is one of the best I
have found with regard to toxins and bio-toxins. It also shows how easy
it would be for terrorists inside the USA to make some toxins from scratch.
BIOLOGICAL TOXINS Toxins are defined
as any toxic substance of natural origin produced by an animal, plant, or microbe.
They are different from chemical agents such as VX, cyanide, or mustard in that
they are not man-made. They are non-volatile, are usually not dermally active
(mycotoxins are an exception), and tend to be more toxic per weight than many
chemical agents. Their lack of volatility also distinguishes them from many of
the chemical threat agents, and is very important in that they would not be either
a persistent battlefield threat or be likely to produce secondary or person to
person exposures. Many of the toxins, such as low molecular weight
toxins and some peptides, are quite stable, where as the stability of the larger
protein bacterial toxins is more variable. The bacterial toxins, such as botulinum
toxins or shiga toxin, tend to be the most toxic in terms of dose required for
lethality (see Table 1, Appendix A), whereas the mycotoxins tend to be among the
least toxic compounds, thousands of times less toxic than the botulinum toxins.
Some toxins are more toxic by the aerosol route than when delivered orally or
parenterally (ricin, saxitoxin, and T2 mycotoxins are examples), whereas botulinum
toxins have lower toxicity when delivered by the aerosol route than when ingested.
Botulinum is so toxic inherently, however, that this characteristic does not limit
its potential as a biological warfare agent. The utility of many toxins
as military weapons is potentially limited by their inherent low toxicity (too
much toxin would be required), or by the fact that some which are very toxic,
such as saxitoxin, can only feasibly be produced in minute quantities. The relationship
between aerosol toxicity and the quantity of toxin required to provide an effective
open-air exposure is shown in Figure 1, Appendix A. The lower the lethal dose
for fifty percent of those exposed (LD50), in micrograms per kilogram, the less
agent would be required to cover a large battlefield sized area. The converse
is also true, and means that for some agents such as ricin, very large quantities
(tons) would be needed for an effective open-air attack. Where toxins
are concerned, incapacitation as well as lethality must be considered. Several
toxins cause significant illness at levels much lower than the level required
for lethality, and are thus militarily significant in their ability to incapacitate
soldiers. This manual will cover four toxins considered to be among
the most likely toxins which could be used against U.S. forces: botulinum toxins,
staphylococcal enterotoxin B (SEB), ricin, and T-2 mycotoxins. ____________________
BOTULINUM TOXINS
SUMMARY Signs and Symptoms: Ptosis, generalized
weakness, dizziness, dry mouth and throat, blurred vision and diplopia, dysarthria,
dysphonia, and dysphagia followed by symmetrical descending flaccid paralysis
and development of respiratory failure. Symptoms begin as early as 24-36 hours
but may take several days after inhalation of toxin. Diagnosis: Clinical
diagnosis. No routine laboratory findings. Biowarfare attack should be suspected
if numerous collocated casualties have progressive descending bulbar, muscular,
and respiratory weakness. Treatment: Intubation and ventilatory assistance
for respiratory failure. Tracheostomy may be required. Administration of botulinum
antitoxin (IND product) may prevent or decrease progression to respiratory failure
and hasten recovery. Prophylaxis: Pentavalent toxoid vaccine (types
A, B, C, D, and E) is available as an IND product for those at high risk of exposure.
Decontamination: Hypochlorite (0.5% for 10-15 minutes) and/or soap
and water. Toxin is not dermally active and secondary aerosols are not a hazard
from patients. OVERVIEW The
botulinum toxins are a group of seven related neurotoxins produced by the bacillus
Clostridium botulinum. These toxins, types A through G, could be delivered by
aerosol over concentrations of troops. When inhaled, these toxins produce a clinical
picture very similar to foodborne intoxication, although the time to onset of
paralytic symptoms may actually be longer than for foodborne cases, and may vary
by type and dose of toxin. The clinical syndrome produced by one or more of these
toxins is known as "botulism". HISTORY AND SIGNIFICANCE
Botulinum toxins have caused numerous cases of botulism when
ingested in improperly prepared or canned foods. Many deaths have occurred
secondary to such incidents. It is feasible to deliver botulinum toxins as a biological
weapon, and other countries have weaponized or are suspected to have weaponized
one or more of this group of toxins. Iraq admitted to a United Nations inspection
team in August of 1991 that it had done research on the offensive use of botulinum
toxins prior to the Persian Gulf War, which occurred in January and February of
that year. Further information given in 1995 revealed that Iraq had not only researched,
but had filled and deployed over 100 munitions with botulinum toxin.
TOXIN CHARACTERISTICS Botulinum toxins
are proteins of approximately 150,000 kD molecular weight which can be produced
from the anaerobic bacterium Clostridium botulinum. As noted above, there are
seven distinct but related neurotoxins, A through G, produced by different strains
of the clostridial bacillus. All seven types act by a similar mechanism. The toxins
produce similar effects when inhaled or ingested, although the time course may
vary depending on the route of exposure and the dose received. Although an aerosol
attack is by far the most likely scenario for the use of botulinum toxins, theoretically
the agent could be used to sabotage food supplies; enemy special forces or terrorists
might use this method in certain scenarios to produce foodborne botulism in those
so targeted. MECHANISM OF TOXICITY
The botulinum toxins as a group are among the most toxic compounds known to man.
Table 1 in Appendix A shows the comparative lethality of selected toxins and chemical
agents in laboratory mice. Botulinum toxin is the most toxic compound per weight
of agent, requiring only 0.001 microgram per kilogram of body weight to kill 50
percent of the animals studied. As a group, bacterial toxins such as botulinum
tend to be the most lethal of all toxins. Note that botulinum toxin is 15,000
times more toxic than VX and 100,000 times more toxic than Sarin, two of the well
known organophosphate nerve agents. Botulinum toxins act by binding
to the presynaptic nerve terminal at the neuromuscular junction and at cholinergic
autonomic sites. These toxins then act to prevent the release of acetylcholine
presynaptically, and thus block neurotransmission. This interruption of neurotransmission
causes both bulbar palsies and the skeletal muscle weakness seen in clinical botulism.
Unlike the situation with nerve agent intoxication, where there is
in effect too much acetylcholine due to inhibition of acetylcholinesterase, the
problem in botulism is lack of the neurotransmitter in the synapse. Thus, pharmacologic
measures such as atropine are not helpful in botulism and could even exacerbate
symptoms. CLINICAL FEATURES
The onset of symptoms of inhalation botulism may vary from 24 to 36 hours, to
several days following exposure. Recent primate studies indicate that the signs
and symptoms may in fact not appear for several days when a low dose of the toxin
is inhaled versus a shorter time period following ingestion of toxin or inhalation
of higher doses. Bulbar palsies are prominent early, with eye symptoms such as
blurred vision due to mydriasis, diplopia, ptosis, and photophobia, in addition
to other bulbar signs such as dysarthria, dysphonia, and dysphagia. Skeletal muscle
paralysis follows, with a symmetrical, descending, and progressive weakness which
may culminate abruptly in respiratory failure. Progression from onset of symptoms
to respiratory failure has occurred in as little as 24 hours in cases of foodborne
botulism. Physical examination usually reveals an alert and oriented
patient without fever. Postural hypotension may be present. Mucous membranes may
be dry and crusted and the patient may complain of dry mouth or even sore throat.
There may be difficulty with speaking and with swallowing. Gag reflex may be absent.
Pupils may be dilated and even fixed. Ptosis and extraocular muscle palsies may
also be observed. Variable degrees of skeletal muscle weakness may be observed
depending on the degree of progression in an individual patient. Deep tendon reflexes
may be present or absent. With severe respiratory muscle paralysis, the patient
may become cyanotic or exhibit narcosis from CO2 retention.
DIAGNOSIS The occurrence of
an epidemic of cases of a descending and progressive bulbar and skeletal paralysis
in afebrile patients points to the diagnosis of botulinum intoxication. Foodborne
outbreaks tend to occur in small clusters and do not generally occur in soldiers
on military rations such as MRE's (Meals, Ready to Eat). Higher numbers of cases
in a theater of operations should raise at least the possibility of a biological
warfare attack with aerosolized botulinum toxin. Foodborne outbreaks are theoretically
possible in troops on normal "A" rations. Individual cases might be
confused clinically with other neuromuscular disorders such as Guillain-Barre
syndrome, myasthenia gravis, or tick paralysis. The edrophonium or Tensilon®
test may be transiently positive in botulism, so it may not distinguish botulinum
intoxication from myasthenia. The cerebrospinal fluid in botulism is normal and
the paralysis is generally symmetrical, which distinguishes it from enteroviral
myelitis. Mental status changes generally seen in viral encephalitis should not
occur with botulinum intoxication. It may become necessary to distinguish
nerve agent and/or atropine poisoning from botulinum intoxication. Nerve agent
poisoning produces copious respiratory secretions and miotic pupils, whereas there
is if anything a decrease in secretions in botulinum intoxication. Atropine overdose
is distinguished from botulism by its central nervous system excitation (hallucinations
and delirium) even though the mucous membranes are dry and mydriasis is present.
The clinical differences between botulinum intoxication and nerve agent poisoning
are depicted in Table 3, Appendix A. Laboratory testing is generally
not helpful in the diagnosis of botulism. Survivors do not usually develop an
antibody response due to the very small amount of toxin necessary to produce clinical
symptoms. Detection of toxin in serum or gastric contents is possible, however,
with a mouse neutralization assay, the only test available, but only in specialized
laboratories. Serum specimens should be drawn from suspected cases and held for
testing at such a facility. MEDICAL MANAGEMENT
Respiratory failure secondary to paralysis of respiratory muscles
is the most serious complication and, generally, the cause of death. Reported
cases of botulism prior to 1950 had a mortality of 60%. With tracheostomy or endotracheal
intubation and ventilatory assistance, fatalities should be less than five percent.
Intensive and prolonged nursing care may be required for recovery (which may take
several weeks or even months). ANTITOXIN: In isolated cases of food-borne
botulism, circulating toxin is present, perhaps due to continued absorption through
the gut wall. Botulinum antitoxin (equine origin) has been used as an investigational
new drug (IND) in those circumstances, and is thought to be helpful. Animal experiments
show that after aerosol exposure, botulinum antitoxin can be very effective if
given before the onset of clinical signs. Administration of antitoxin is reasonable
if disease has not progressed to a stable state. A trivalent equine
antitoxin has been available from the Centers for Disease Control for cases of
foodborne botulism. This product has all the disadvantages of a horse serum product,
including the risks of anaphylaxis and serum sickness. A "despeciated" equine
heptavalent antitoxin (against types A, B, C, D, E, F, and G) has been prepared
by cleaving the Fc fragments from horse IgG molecules, leaving F(ab)2 fragments.
This product is under advanced development, and is currently available under IND
status. Its efficacy is inferred from its performance in animal studies. Disadvantages
include rapid clearance by immune elimination, as well as a theoretical risk of
serum sickness. Use of the antitoxin requires skin testing for horse
serum sensitivity prior to administration. Skin testing is performed by injecting
0.1 ml of a 1 to 10 dilution of antitoxin intradermally and monitoring the patient
for 20 minutes. If the injection site becomes hyperemic (>0.5 cm diameter),
or the patient develops fever, chills, hypotension, skin rash, respiratory difficulty,
nausea, vomiting and/or generalized itching, the skin test is considered positive.
If no allergic symptoms are observed, the antitoxin is administered intravenously,
10 mls over 20 minutes. This dose is repeated until there is no more improvement.
With a positive skin test, desensitization is carried out by administering 0.01
- 0.1 ml of antitoxin subcutaneously, gradually increasing the dose every 20 minutes
until 2.0 ml can be sustained without a marked reaction.
PROPHYLAXIS A pentavalent toxoid of Clostridium botulinum toxin
types A, B, C, D, and E is available under an IND status. This product has been
administered to several thousand volunteers and occupationally at-risk workers,
and induces serum antitoxin levels that correspond to protective levels in experimental
animal systems. The currently recommended schedule (0, 2, and 12 weeks, then a
1 year booster) induces protective antibody levels in greater than 90 percent
of vaccines after one year. Adequate antibody levels are transiently induced after
three injections, but decline prior to the one year booster. Contraindications
to the vaccine include sensitivities to alum, formaldehyde, and thimerosal, or
hypersensitivity to a previous dose. Reactogenicity is mild, with two to four
percent of vaccines reporting erythema, edema, or induration at the local site
of injection which peaks at 24 to 48 hours, then dissipates. The frequency of
such local reactions increases with each subsequent inoculation; after the second
and third doses, seven to ten percent will have local reactions, with higher incidence
(up to twenty percent or so) after boosters. Severe local reactions are rare,
consisting of more extensive edema or induration. Systemic reactions are reported
in up to three percent, consisting of fever, malaise, headache, and myalgia. Incapacitating
reactions (local or systemic) are uncommon. The vaccine should be stored at refrigerator
temperatures (not frozen). Three or more vaccine doses (0, 2, and
12 weeks, then at 1 year if possible, all by deep subcutaneous injection) are
recommended only to selected individuals or groups judged at high risk for exposure
to botulinum toxin aerosols. There is no indication at present for use of
botulinum antitoxin as a prophylactic modality except under extremely specialized
circumstances. _______________________
STAPHYLOCOCCAL ENTEROTOXIN B SUMMARY
Signs and Symptoms: From 3-12 hours after aerosol exposure, sudden
onset of fever, chills, headache, myalgia, and nonproductive cough. Some patients
may develop shortness of breath and retrosternal chest pain. Fever may last 2
to 5 days, and cough may persist for up to 4 weeks. Patients may also present
with nausea, vomiting, and diarrhea if they swallow toxin. Higher exposure can
lead to septic shock and death. Diagnosis: Diagnosis is clinical.
Patients present with a febrile respiratory syndrome without CXR abnormalities.
Large numbers of soldiers presenting with typical symptoms and signs of SEB pulmonary
exposure would suggest an intentional attack with this toxin. Treatment:
Treatment is limited to supportive care. Artificial ventilation might be needed
for very severe cases, and attention to fluid management is important.
Prophylaxis: Use of protective mask. There is currently no human vaccine available
to prevent SEB intoxication. Decontamination: Hypochlorite (0.5% for
10-15 minutes) and/or soap and water. Destroy any food that may have been contaminated.
OVERVIEW Staphylococcus aureus
produces a number of exotoxins, one of which is Staphylococcal enterotoxin B,
or SEB. Such toxins are referred to as exotoxins since they are excreted from
the organism; however, they normally exert their effects on the intestines and
thereby are called enterotoxins. SEB is one of the pyrogenic toxins that commonly
causes food poisoning in humans after the toxin is produced in improperly handled
foodstuffs and subsequently ingested. SEB has a very broad spectrum of biological
activity. This toxin causes a markedly different clinical syndrome when inhaled
than it characteristically produces when ingested. Significant morbidity is produced
in individuals who are exposed to SEB by either portal of entry to the body.
HISTORY AND SIGNIFICANCE SEB has
caused countless endemic cases of food poisoning. Often these cases have been
clustered, due to common source exposure in a setting such as a church picnic
or passengers eating the same toxin-contaminated food on an airliner. Although
this toxin would not be likely to produce significant mortality on the battlefield,
it could render up to 80 percent or more of exposed personnel clinically ill and
unable to perform their mission for a fairly prolonged period of time. Therefore,
even though SEB is not generally thought of as a lethal agent, it may incapacitate
soldiers for up to two weeks, making it an extremely important toxin to consider.
TOXIN CHARACTERISTICS Staphylococcal
enterotoxins are extracellular products produced by coagulase-positive staphylococci.
They are produced in culture media and also in foods when there is overgrowth
of the staph organisms. At least five antigenically distinct enterotoxins have
been identified, SEB being one of them. These toxins are heat stable. SEB causes
symptoms when inhaled at very low doses in humans: a dose of several logs lower
than the lethal dose by the inhaled route would be sufficient to incapacitate
50 percent of those soldiers so exposed. This toxin could also be used (theoretically)
in a special forces or terrorist mode to sabotage food or low volume water supplies.
MECHANISM OF TOXICITY Staphylococcal
enterotoxins produce a variety of toxic effects. Inhalation of SEB can induce
extensive pathophysiological changes to include widespread systemic damage and
even septic shock. Many of the effects of staphylococcal enterotoxins are mediated
by interactions with the host's own immune system. The mechanisms of toxicity
are complex, but are related to toxin binding directly to the major histocompatibility
complex that subsequently stimulates the proliferation of large numbers of T cell
lymphocytes. Because these exotoxins are extremely potent activators of T cells,
they are commonly referred to as bacterial superantigens. These superantigens
stimulate the production and secretion of various cytokines, such as tumor necrosis
factor, interferon-(, interleukin-1 and interleukin-2, from immune system cells.
Released cytokines are thought to mediate many of the toxic effects of SEB.
CLINICAL FEATURES Relevant battlefield
exposures to SEB are projected to cause primarily clinical illness and incapacitation.
However, higher exposure levels can lead to septic shock and death. Intoxication
with SEB begins 3 to 12 hours after inhalation of the toxin. Victims may experience
the sudden onset of fever, headache, chills, myalgias, and a nonproductive cough.
More severe cases may develop dyspnea and retrosternal chest pain. Nausea, vomiting,
and diarrhea will also occur in many patients due to inadvertently swallowed toxin,
and fluid losses can be marked. The fever may last up to five days and range from
103 to 106o F, with variable degrees of chills and prostration. The cough may
persist up o four weeks, and patients may not be able to return to duty for two
weeks. Physical examination in patients with SEB intoxication is often
unremarkable. Conjunctival injection may be present, and postural hypotension
may develop due to fluid losses. Chest examination is unremarkable except in the
unusual case where pulmonary edema develops. The chest X-ray is also generally
normal, but in severe cases increased interstitial markings, atelectasis, and
possibly overt pulmonary edema or an ARDS picture may develop.
DIAGNOSIS As is the case with botulinum toxins, intoxication
due to SEB inhalation is a clinical and epidemiologic diagnosis. Because
the symptoms of SEB intoxication may be similar to several respiratory pathogens
such as influenza, adenovirus, and mycoplasma, the diagnosis may initially be
unclear. All of these might present with fever, nonproductive cough, myalgia,
and headache. SEB attack would cause cases to present in large numbers over a
very short period of time, probably within a single 24 hour period. Naturally
occurring pneumonias or influenza would involve patients presenting over a more
prolonged interval of time. Naturally occurring staphylococcal food poisoning
cases would not present with pulmonary symptoms. SEB intoxication tends to progress
rapidly to a fairly stable clinical state, whereas pulmonary anthrax, tularemia
pneumonia, or pneumonic plague would all progress if left untreated. Tularemia
and plague, as well as Q fever, would be associated with infiltrates on chest
radiographs. Nerve agent intoxication would cause fasciculations and
copious secretions, and mustard would cause skin lesions in addition to pulmonary
findings; SEB inhalation would not be characterized by these findings. The dyspnea
associated with botulinum intoxication is associated with obvious signs of muscular
paralysis, bulbar palsies, lack of fever, and a dry pulmonary tree due to cholinergic
blockade; respiratory difficulties occur late rather than early as with SEB inhalation.
Laboratory findings are not very helpful in the diagnosis of SEB intoxication.
A nonspecific neutrophilic leukocytosis and an elevated erythrocyte sedimentation
rate may be seen, but these abnormalities are present in many illnesses. Toxin
is very difficult to detect in the serum by the time symptoms occur; however,
a serum specimen should be drawn as early as possible after exposure. Data from
rabbit studies clearly show that SEB in the serum is transient; however, it accumulates
in the urine and can be detected for several hours post exposure. Therefore, urine
samples should be obtained and tested for SEB. High SEB concentrations inhibit
kidney function. Because most patients will develop a significant antibody response
to the toxin, acute and convalescent serum should be drawn which may be helpful
retrospectively in the diagnosis. MEDICAL MANAGEMENT
Currently, therapy is limited to supportive care. Close attention
to oxygenation and hydration are important, and in severe cases with pulmonary
edema, ventilation with positive end expiratory pressure and diuretics might be
necessary. Acetaminophen for fever, and cough suppressants may make the patient
more comfortable. The value of steroids is unknown. Most patients would be expected
to do quite well after the initial acute phase of their illness, but most would
generally be unfit for duty for one to two weeks.
PROPHYLAXIS Although there is currently no human vaccine for
immunization against SEB intoxication, several vaccine candidates are in development.
Preliminary animal studies have been encouraging and a vaccine candidate is nearing
transition to advanced development and safety and immunogenicity testing in man.
Experimentally, passive immunotherapy can reduce mortality, but only when given
within 4-8 hours after inhaling SEB. _____________________________
RICIN
SUMMARY Signs and Symptoms: Weakness, fever, cough
and pulmonary edema occur 18-24 hours after inhalation exposure, followed by severe
respiratory distress and death from hypoxemia in 36-72 hours.
Diagnosis: Signs and symptoms noted above in large numbers of geographically clustered
patients could suggest an exposure to aerosolized ricin. The rapid time course
to severe symptoms and death would be unusual for infectious agents. Laboratory
findings are nonspecific but similar to other pulmonary irritants which cause
pulmonary edema. Specific serum ELISA is available. Acute and convalescent sera
should be collected. Treatment: Management is supportive and should
include treatment for pulmonary edema. Gastric decontamination measures should
be used if ingested. Prophylaxis: There is currently no vaccine or
prophylactic antitoxin available for human use, although immunization appears
promising in animal models. Use of the protective mask is currently the best protection
against inhalation. Decontamination: Weak hypochlorite solutions and/or
soap and water can decontaminate skin surfaces. Ricin is not volatile, so secondary
aerosols are generally not a danger to health care providers.
OVERVIEW Ricin is a potent protein toxin derived from the beans
of the castor plant (Ricinus communis ). Castor beans are ubiquitous worldwide,
and the toxin is fairly easily produced from them. Ricin is therefore a potentially
widely available toxin. When inhaled as a small particle aerosol, this toxin may
produce pathologic changes within 8 hours and severe respiratory symptoms followed
by acute hypoxic respiratory failure in 36-72 hours. When ingested, ricin causes
severe gastrointestinal symptoms followed as well by vascular collapse and death.
This toxin may also cause disseminated intravascular coagulation, microcirculatory
failure and multiple organ failure if given intravenously in laboratory animals.
HISTORY AND SIGNIFICANCE Ricin's
significance as a potential biological warfare toxin relates in part to its wide
availability. Worldwide, one million tons of castor beans are processed annually
in the production of castor oil; the waste mash from this process is approximately
five percent ricin by weight. The toxin is also quite stable and extremely toxic
by several routes of exposure, including the respiratory route. Ricin is said
to have been used in the assassination of Bulgarian exile Georgi Markov in London
in 1978. Markov was attacked with a specially engineered weapon disguised as an
umbrella which implanted a ricin- containing pellet into his body.
TOXIN CHARACTERISTICS Ricin is actually made
up of two hemagglutinins and two toxins. The toxins, RCL III and RCL IV, are dimers
of about 66,000 daltons molecular weight. The toxins are made up of two polypeptide
chains, an A and a B chain, which are joined by a disulfide bond. Ricin can be
produced relatively easily and inexpensively in large quantities in a fairly low
technology setting. It is of marginal toxicity in terms of its LD50 in comparison
to toxins such as botulinum and SEB (incapacitating dose), so an enemy would have
to produce it in larger quantities to cover a significant area on the battlefield
(see Figure 1, Appendix A). This might limit large-scale use of ricin by an adversary.
Ricin can be prepared in liquid or crystalline form, or it can be lyophilized
to make it a dry powder. It could be disseminated by an enemy as an aerosol, or
it could be used as a sabotage, assassination, or terrorist weapon.
MECHANISM OF TOXICITY Ricin is very toxic
to cells. It acts by inhibiting protein synthesis. The B chain binds to cell surface
receptors and the toxin-receptor complex is taken into the cell; the A chain has
endonuclease activity and extremely low concentrations will inhibit protein synthesis.
In rodents, the histopathology of aerosol exposure is characterized by necrotizing
airway lesions causing tracheitis, bronchitis, bronchiolitis, and interstitial
pneumonia with perivascular and alveolar edema. There is a latent period of 8
hours post inhalation exposure before histologic lesions were observed in animal
models. In rodents, ricin is more toxic by the aerosol route compared to other
routes of exposure. There is little toxicity data in humans. The exact
cause of morbidity and mortality would be dependent upon the route of exposure.
Aerosol exposure in man would be expected to cause acute lung injury, pulmonary
edema secondary to increased capillary permeability, and eventual acute hypoxic
respiratory failure. CLINICAL FEATURES
The clinical picture in intoxicated victims would depend on the route
of exposure. After aerosol exposure, signs and symptoms would depend on the dose
inhaled. Accidental sublethal aerosol exposures which occurred in humans in the
1940's were characterized by onset of the following symptoms in four to eight
hours: fever, chest tightness, cough, dyspnea, nausea, and arthralgias. The onset
of profuse sweating some hours later was commonly the sign of termination of most
of the symptoms. Although lethal human aerosol exposures have not been described,
the severe pathophysiologic changes seen in the animal respiratory tract, including
necrosis and severe alveolar flooding, are probably sufficient to cause if enough
toxin is inhaled. Time to death in experimental animals is dose dependent, occurring
36-72 hours post inhalation exposure. Humans would be expected to develop severe
lung inflammation with progressive cough, dyspnea, cyanosis and pulmonary edema.
By other routes of exposure, ricin is not a direct lung irritant;
however, intravascular injection can cause minimal pulmonary perivascular edema
due to vascular endothelial injury. Ingestion causes gastrointestinal hemorrhage
with hepatic, splenic, and renal necrosis. Intramuscular administration causes
severe local necrosis of muscle and regional lymph nodes with moderate visceral
organ involvement. DIAGNOSIS
An attack with aerosolized ricin would be, as with many biological warfare agents,
primarily diagnosed by the clinical and epidemiological setting. Acute lung injury
affecting a large number of cases in a war zone where an attack could occur should
raise suspicion of an attack with a pulmonary irritant such as ricin, although
other pulmonary pathogens could present with similar signs and symptoms. Other
biological threats, such as SEB, Q fever, tularemia, plague, and some chemical
warfare agents like phosgene, need to be included in a differential diagnosis.
Ricin intoxication would be expected to progress despite treatment with antibiotics,
as opposed to an infectious process. There would be no mediastinitis as seen with
inhalation anthrax. SEB would be different in that most patients would not progress
to a life-threatening syndrome but would tend to plateau clinically. Phosgene-induced
acute lung injury would progress much faster than that caused by ricin.
Additional supportive clinical or diagnostic features after aerosol exposure to
ricin may include the following: bilateral infiltrates on chest radiographs, arterial
hypoxemia, neutrophilic leukocytosis, and a bronchial aspirate rich in protein
compared to plasma which is characteristic of high permeability pulmonary edema.
Specific ELISA testing on serum or immunohistochemical techniques for direct tissue
analysis may be used where available to confirm the diagnosis. Ricin is
an extremely immunogenic toxin, and acute as well as convalescent sera should
be obtained from survivors for measurement of antibody response.
MEDICAL MANAGEMENT Management of ricin intoxicated
patients again depends on the route of exposure. Patients with pulmonary intoxication
are managed by appropriate treatment for pulmonary edema and respiratory support
as indicated. Gastrointestinal intoxication is best managed by vigorous
gastric decontamination with lavage and superactivated charcoal, followed by use
of cathartics such as magnesium citrate. Volume replacement of GI fluid losses
is important. In percutaneous exposures, treatment would be primarily supportive.
PROPHYLAXIS The protective
mask is effective when worn in preventing aerosol exposure. Although a vaccine
is not currently available, candidate vaccines are under development which are
immunogenic and confer protection against lethal aerosol exposures in animals.
Prophylaxis with such a vaccine is the most promising defense against a biological
warfare attack with ricin. _________________________________
TRICHOTHECENE MYCOTOXINS (T2)
SUMMARY Signs and Symptoms: Exposure causes
skin pain, pruritus, redness, vesicles, necrosis and sloughing of epidermis. Effects
on the airway include nose and throat pain, nasal discharge, itching and sneezing,
cough, dyspnea, wheezing, chest pain and hemoptysis. Toxin also produces effects
after ingestion or eye contact. Severe poisoning results in prostration, weakness,
ataxia, collapse, shock, and death. Diagnosis: Should be suspected
if an aerosol attack occurs in the form of "yellow rain" with droplets of yellow
fluid contaminating clothes and the environment. Confirmation requires testing
of blood, tissue and environmental samples. Treatment: There is no
specific antidote. Superactivated charcoal should be given orally if swallowed.
Prophylaxis: The only defense is to wear a protective mask and clothing
during an attack. No specific immunotherapy or chemotherapy is available for use
in the field. Decontamination: The outer uniform should be removed
and exposed skin should be decontaminated with soap and water. Eye exposure should
be treated with copious saline irrigation. Once decontamination is complete, isolation
is not required. OVERVIEW The
trichothecene mycotoxins are low molecular weight (250-500 daltons) nonvolatile
compounds produced by filamentous fungi (molds) of the genera Fusarium, Myrotecium,
Trichoderma, Stachybotrys and others. The structures of approximately 150 trichothecene
derivatives have been described in the literature. These substances are relatively
insoluble in water but are highly soluble in ethanol, methanol and propylene glycol.
The trichothecenes are extremely stable to heat and ultraviolet light inactivation.
Heating to 500o F for 30 minutes is required for inactivation, while brief exposure
to NaOH destroys toxic activity. The potential for use as a BW toxin
was demonstrated to the Russian military shortly after World War II when flour
contaminated with species of Fusarium was baked into bread that was ingested by
civilians. Some developed a protracted lethal illness called alimentary toxic
aleukia (ATA) characterized by initial symptoms of abdominal pain, diarrhea, vomiting,
prostration, and within days fever, chills, myalgias and bone marrow depression
with granulocytopenia and secondary sepsis. Survival beyond this point
allowed the development of painful pharyngeal/laryngeal ulceration and diffuse
bleeding into the skin (petechiae and ecchymoses), melena, bloody diarrhea, hematuria,
hematemesis, epistaxis and vaginal bleeding. Pancytopenia, and gastrointestinal
ulceration and erosion were secondary to the ability of these toxins to profoundly
arrest bone marrow and mucosal protein synthesis and cell cycle progression through
DNA replication. HISTORY AND SIGNIFICANCE
Mycotoxins allegedly have been used in aerosol form ("yellow rain")
to produce lethal and nonlethal casualties in Laos (1975-81), Kampuchea (1979-81),
and Afghanistan (1979-81). It has been estimated that there were more than 6,300
deaths in Laos, 1,000 in Kampuchea, and 3,042 in Afghanistan. The alleged victims
were usually unarmed civilians or guerrilla forces. These groups were not protected
with masks and chemical protective clothing and had little or no capability of
destroying the attacking enemy aircraft. These attacks were alleged to have occurred
in remote jungle areas which made confirmation of attacks and recovery of agent
extremely difficult. Much controversy has centered about the veracity of eyewitness
and victim accounts, but there is enough evidence to make agent use in these areas
highly probable. CLINICAL FEATURES
T2 and other mycotoxins may enter the body through the skin and aerodigestive
epithelium. They are fast acting potent inhibitors of protein and nucleic acid
synthesis. Their main effects are on rapidly proliferating tissues such as the
bone marrow, skin, mucosal epithelia, and germ cells. In a successful
BW attack with trichothecene toxin (T2), the toxin(s) will adhere to and penetrate
skin, be inhaled, and swallowed. Clothing will be contaminated and serve as a
reservoir for further toxin exposure. Early symptoms beginning within minutes
of exposure include burning skin pain, redness, tenderness, blistering, and progression
to skin necrosis with leathery blackening and sloughing of large areas of skin
in lethal cases. Nasal contact is manifested by nasal itching and pain, sneezing,
epistaxis and rhinorrhea; pulmonary/tracheobronchial toxicity by dyspnea, wheezing,
and cough; and mouth and throat exposure by pain and blood tinged saliva and sputum.
Anorexia, nausea, vomiting and watery or bloody diarrhea with abdominal
crampy pain occurs with gastrointestinal toxicity. Eye pain, tearing, redness,
foreign body sensation and blurred vision may follow entry of toxin into the eyes.
Skin symptoms occur in minutes to hours and eye symptoms in minutes. Systemic
toxicity is manifested by weakness, prostration, dizziness, ataxia, and loss of
coordination. Tachycardia, hypothermia, and hypotension follow in fatal cases.
Death may occur in minutes, hours or days. The commonest symptoms were vomiting,
diarrhea, skin involvement with burning pain, redness and pruritus, rash or blisters,
bleeding, and dyspnea. DIAGNOSIS
Rapid onset of symptoms in minutes to hours supports a diagnosis of a chemical
or toxin attack. Mustard agents must be considered but they have an odor, are
visible, and can be rapidly detected by a field available chemical test. Symptoms
from mustard toxicity are also delayed for several hours after which mustard can
cause skin, eye and respiratory symptoms. Staphylococcal enterotoxin B delivered
by an aerosol attack can cause fever, cough, dyspnea and wheezing but does not
involve the skin and eyes. Nausea, vomiting, and diarrhea may follow swallowing
of inhaled toxin. Ricin inhalation can cause severe respiratory distress, cough,
nausea and arthralgias. Swallowed agent can cause vomiting, diarrhea, and gastrointestinal
bleeding, but it spares the skin, nose and eyes. Specific diagnosis
of T-2 mycotoxins in the form of a rapid diagnostic test is not presently available
in the field. Removal of blood, tissue from fatal cases, and environmental samples
for testing using a gas liquid chromatography-mass spectrometry technique will
confirm the toxic exposure. This system can detect as little as 0.1-1.0 ppb of
T-2. This degree of sensitivity is capable of measuring T-2 levels in the plasma
of toxin victims. MEDICAL MANAGEMENT
Use of a chemical protective mask and clothing prior to and during a mycotoxin
aerosol attack will prevent illness. If a soldier is unprotected during an attack
the outer uniform should be discarded within 4 hours and decontaminated by exposure
to 5% hypochlorite for 6-10 hours. The skin should be thoroughly washed with soap
and uncontaminated water if available. The M291 skin decontamination kit should
also be used to remove skin adherent T-2. Superactive charcoal can absorb swallowed
T-2 and should be administered to victims of an unprotected aerosol attack. The
eyes should be irrigated with normal saline or water to remove toxin. No specific
antidote or therapeutic regimen iscurrently field available. All therapy is symptomatic
and supportive. PROPHYLAXIS
Physical protection of the skin and airway are the only proven effective methods
of protection during an attack. Immunological (vaccines) and chemoprotective pretreatments
are being studied in animal models, but are not available for field use by the
warfighter.
TERRIFYING
ARTICLE
ON WARFARE GRADE TOXINS.
PLEASE DON'T READ THIS JUST BEFORE GOING TO BED. The
American Spectator-- James Ring Adams-- What terror weapon is Saddam
Hussein hiding from U.N. inspectors, even at the risk of renewed U.S. bombing?
The evidence points to a new form of one of the nastiest villains of the Cold
War, Yellow Rain. This blistering, highly lethal agent, scientifically
a "mycotoxin," a form of poison produced by microscopic fungi, emerged at the
beginning of the 1980's in Soviet surrogate attacks on anti-Communist insurgents
in Laos and Afghanistan. Strong complaints from the Reagan State Department apparently
persuaded the Soviet Union to stop using it. But U.S. diplomats were scarred by
a loud counter attack from 'Western apologists unwilling to admit that Moscow
was violating a major treaty against biological Weapons. '[his threat is back,
along with a more widely acknowledged range of biological weapons, hut the psychological
denial by the disarmament lobby has left the West largely helpless to deal with
it. The arms inspectors at the U.N. Special Commission (UNSCOM) now
say outright they were on the trail of a major biological weapons system when
Saddam Hussein cut them off this January. But they clam up when pressed for more
specifics. UNSCOM spokesman Ewen Buchanan explains that they don't want to tip
Iraq to what they know, which he hints is quite a lot.
The Aflatoxin
Bomb But it was Iraq itself which put Yellow Rain back on the
terror weapon hot list and presented LINSCOM with its great est mystery. In July
1995, officials in Baghdad revealed to the inspectors that not only had they experimented
with a sub stance called Aflatoxin, but they had loaded it into missile warheads
and gravity bombs during the Gulf War and given commanders pre-delegated authority
to use it. After the cease-fire, their stockpile was destroyed, the Iraqis added.
Nothing about this story added up. Baghdad's count of the number munitions
loaded with Aflatoxin kept changing, fluctuating up and down from the original
report of four al-Hussein missiles and seven R-4oo gravity bombs. Then the reported
production facility at Fudaliyah seemed totally inadequate to growing the quantity
Ira(l said it held. But the biggest question of all was: Why Aflatoxin?
It was simply a lousy candidate for a battlefield weapon. The toxin could ruin
your peanut crop, as it sometimes does in the U.S.. and in the long run might
cause liver cancer in humans. But it didn't have the immediate drop-dead action
that could make a difference in a fight. It was no cinch to handle, either. It
was hard to dissolve, even for a mycotoxin, so you wound up making a munition
filled with solvent. As one UNSCOM specialist was food of saying, you would get
hurt by an Aflatox in bomb mainly if it fell on your head Yet there's
a plausible report that an agent of this sort was turned on American forces during
the Gulf War, and it did harm. At 3 am, on January 19, 1991, flash of red light
and a loud shock wave woke nearly 750 Seabees of the 24th Naval Mobile Construction
Battalion camped near al Jitbayl in northern Saudi Arabia. A general alarm sounded,
with a radio message warning of "a confirmed chemical agent." As troops struggled
into their masks and rubberized suits, they noticed a "dense yellowish mist" float
ing over the camp. Those who didn't suit in time began to choke and felt a burning
on their skin. Exposed areas later broke out in rashes and blisters, which turned
to ulcerating sores. The New York Times surveyed 152 veterans of the unit
in Sep tember 1996 and found that 114 report ed chronic post war illness.
The Pentagon said Patriot missiles caused the explosion and blamed the
symptoms on a toxic propellant released from an Iraqi SCUD as it broke up in the
air. But the details don't fit For one thing, the nitric acid propellant should
have corroded the rubber suits, but they were unaffected. According to a paper
by Jonathan Tucker of the Monterey Institute of Inter national Studies in California,
no SCUD attacks were reported that night. Tucker finds it possible instead that
Patriot missiles were launched against an aircraft equipped to spray a biological
weapon. Unit veterans strongly suspect a cover-up. A communications officer later
stated in an affidavit that radio operators in the command bunkers were ordered
to burn the log pages covering the incident. Explanations of these
mysteries were lacking until this spring, when a former UNSCOM inspector named
Terry Taylor spilled the beans. At a symposium in London he remarked that Iraq's
"Aflatoxin bomb" looked like a cover for another agent, a quick-acting battlefield
toxin, was produced with the same fermenting process. UNSCOM officials don't hide
their annoyance that their hand was tipped even this much. When one asks them
about the likely candidate for the secret substance, one or more of the chothecenes,
they roll their eyes. Peanut Mold or Yellow Rain?
The txichothecene family of mycotoxins produced what the Reagan Administration
identified as the active agent in Yellow Rain, and it is nasty. These toxins immediately
attack eyes, skin, and respiration. As blistering agents, they do up to forty
times more damage than the Lewisite and mustard gas of World War I. The skin forms
pus-filled welts and sloughs off, giving rise to symptoms like those noted at
al-Jubayl. As the toxins bum their way through throat, stomach, and intestines,
they cause vomiting and bloody diarrhea. Depending on exposure, death can come
in minutes. Lesser amounts can cause long-term suppression of the immune system.
Unlike Aflatoxin, the trichothecenes dissolve fairly readily. (The
term "yellow rain" referred to the dispersal agent used in the early 1980's, which
spread the toxin in oily, sticky yellow droplets.) But UNSCOM specialists doubt
that this weapon has returned in its original form. The toxin then most frequently
identified, T-2, was considered a battlefield failure since its dispersal radius
was still limited. There are other choices, however Some mycotoxins
are named for the species of fungus that produces them, but the trichothecenes
are classed together by their chemical structure. One type of toxin can be produced
by several different species, and a prolific species like fusarium, stachybotris,
and, yes, penicilliurn can produce several different trichothecenes. These fungi
are easily found in nature. (Stachybotris made a name for itself in New York City
recently when a bloom of the mold closed down a newly renovated public library
on Staten Island.) Their poisons can be even more dead ly when combined
together or mixed in a "cocktail" with chemicals like mustard gas. Agricultural
researchers have found that aflatoxin potentiates both T-2 and another "yellow
rain" component called DAS (diacetoxyscirpenol), meaning that the harm caused
by the agents together is more severe than each would cause alone. The toxins
can be synthesized or altered with artificial ingredients. Any number of breakthroughs
could have occurred in the thirteen years since "yellow rain" went underground.
And there is a nagging, still unrefuted report that Iraq is feeding off the work
of the masterminds of this terror weapon, the biological warriors of the former
Soviet Union. Incident at Majnoon A battle from
the most desperate days of the Iran-Iraq war hangs over this whole issue. At the
end of 1983, Iranian human wave attacks were pushing Iraqi forces back through
the marshes around Majnoon Island when Iraq unleashed a new chemical weapon. European
doctors reported mustard gas, canisters of which were later found by a U.N. mission,
but they also detected trace amounts of T-2. At the same time, Israeli intelligence
leaked a report about Iraqi negotiations with the Soviet Union for some spectacular
new weapon to break the stalemate with Iraq. According to this analysis,
Iraq asked specifically for a CBW system during the November 14, 1983 visit to
Baghdad of Vladimir Mordvinov, deputy chairman of the USSR Committee for Foreign
Economic Relations. Mordvinov kicked the request back to Moscow, and two weeks
later his boss Yakov Ryahov flew to Baghdad to make arrangements. Radio Moscow
reported with fine irony that the talks "provided for help in reclaiming an oil
held." This account fits the chronology of Iraq's homegrown biowar
program, which it claims didn't begin in earnest until 1985. It also explains
why Iraq was able to make what UNSCOM called such remarkable gains in such a short
time. It implies, bluntly, that Baghdad learned the secrets of Yellow
Rain from its Soviet friends. This report quickly became a hot potato and remains
one to this day. Central Intelligence Agency sources warned reporters
not to trust the findings of the Belgian specialist Aubin Heyndrickx who was treating
the Iranian victims of Majnoon. Senior Israeli officials repudiated the work of
their own analyst. The State Department fell silent about Yellow Rain. It was
almost as if some secret deal had been struck to abandon the issue if the attacks
ceased. The Cold War's Biggest Secret With the advent of Mikhail Gorbachev
and perestroika, the issue was forgotten, until a major defection brought it suddenly
to the fore. In October 1989, a scientist from Leningrad named Vladimir Pasechnik
arrived in Toulouse, France, to buy chemical equipment for his research laboratory,
the Institute of Ultra Pure Biochemical Preparations. in the course of fifteen
years spent building this institute, Pasechnik had discovered that he was part
of a vast military project called the Biopreparat, devoted to developing new biological
weapons. Conscience stricken, he called the British embassy in Paris, and was
quickly hustled across the channel. His debriefing confirmed the worst fears of
western intelligence. The Soviet military was spending bil lions of rubles and
employing 15,000 workers in plants capable of mass producing biological weapons.
Biopreparat researchers had used genetic engineering to produce new antibiotic-resistant
strains of diseases such as tularemia and pneumonic plague. The revelations prompted
British Prime Minister Margaret Thatcher and U.S. President George Bush to confront
Gorbachev directly. With the breakup of the Soviet Union, the allies
continued to pressure Russian President Boris Yeltsin, who promised to dismantle
the Biopreparat. The whole Soviet project was a blatant violation of the 1972
Biological and Toxin Weapons Convention, but the West softened its public complaints
for fear of causing Yeltsin problems with his military.' In spite
of Yeltsin's promise, there are worries that he had neither the will nor the control
to carry it out. He delegated the job to the notorious General Anatoly Kuntsevich,
the former chemical troops commander and political hard-liner. Kuntsevich was
fired in 1994 and later fell under suspicion of illegally selling chemical weapons
precursors to Syria.
Editor: Balaam's Ass Speaks--
This article contained more, and I don't expect to get it later. I
think this is enough to satisfy you that War with any Middle Eastern country would
unleash a holocaust against the USA which we absolutely are NOT prepared to resist
or to survive. Millions could be taken out with these and other biological
agents. We also see how the bible test below could be fulfilled in our time:
Speaking of the future destruction of Babylon: Isaiah
13:8 And they shall be afraid: pangs and sorrows shall take hold of them; they
shall be in pain as a woman that travaileth: they shall be amazed one at another;
their faces shall be as flames. ______________________________________LINKS:*
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