Guillain-Barré syndrome

There are several natural and artificial factors that mimic the effects of chemical warfare agents, thereby causing unwarranted alarm and confusion on the battlefield. Symptoms associated with chemical warfare include paralysis, muscle tremors, heavy salivation, severe burns, blistering, and corrosive skin injuries among others. Similar symptoms can be produced from a variety of environmental sources, artificial and natural. This article reviews several published and unpublished examples of environmental factors that produce syndromes similar to those caused by these agents. Examples of such mimics include pesticides, blistering exudates from insects and plants, various types of bites, and naturally occurring diseases. The potential for confusion caused by these factors is discussed and means of discriminating between warfare agents and naturally occurring events are identified. Recommendations for the use of this information and for needed research are also discussed.

Introduction

In 1997, several U.S. Marines on an exercise in central Arizona experienced severe blistering symptoms. Several individuals exhibited very large blisters on their legs, arms, and faces, and another victim developed a severe case of conjunctivitis in one eye. Military medical personnel could not identify the source of the outbreak. However, because the Marines did not appear to be in distress, most of the victims were returned to duty. Interestingly, the appearance of the blisters reminded the Marines of images they had seen during training sessions on chemical warfare. Fearing possible exposure to blistering agents, some Marines, including at least one company grade officer, were dissatisfied with their medical treatment and threatened to seek civilian medical care in the nearest city.

A subsequent investigation by U.S. Navy preventive medicine personnel identified the probable cause of the blistering disease as a small rove beetle (family: Staphylinidae) which exudes a strong blistering agent when disturbed.1 These beetles had probably been flooded out of their normal rodent-burrow habitats by unusually heavy rains and were attracted to the lights of the Marine encampment. As the beetles brushed against the humans, the resulting slap stimulated the insects to exude blistering agent, causing the large blebs and the conjunctivitis noted in the blistering disease. The outbreak ended a few days after the last heavy rain. The Marines had in effect suffered a chemical attack, although the attack was not human in origin.

Although limited in scope, this episode is of interest because of the response of the Marines to the perceived threat of chemical warfare. It demonstrates the confusion and alarm that ensues when military personnel cannot distinguish between the symptoms caused by chemical warfare agents and similar symptoms caused by common environmental factors. These environmental factors are "mimics" of chemical warfare agents.

During the blistering disease incident in Arizona, where there was no credible threat of a chemical warfare agent, it took several weeks to find a probable cause. A definite cause was never identified. The alarm among the Marines was significant, but in a real wartime scenario, the confusion could be much worse. One potential way of reducing such confusion would be the identification of common mimics of chemical warfare agents

before arrival in the area of operations. If such knowledge was available, medical personnel would be better able to discriminate between indigenous maladies and the emergencies caused by intentional use of warfare agents. As the Arizona incident demonstrates, nonmedical personnel can also benefit from this knowledge.

On the other hand, such information might delay proper treatment for chemical agent victims. Indeed, the speed with which medical personnel obtain proper diagnosis and the rapidity with which they apply proper therapeutic measures can greatly influence mortality rates after a chemical attack.2 Conversely, false alarms can also degrade a unit's war-fighting capabilities. The defensive measures used by the U.S. military on the chemical battlefield are effective, but they are also very risky and are likely to impair performance and decision making.3 For example, Headly4 noted that antidotal atropine increases skin and rectal temperature and compromises thermoregulation, especially in soldiers wearing protective clothing or working in hot environments.

Unnecessary alerts might also result in the wasteful employment of limited protective gear, requiring rapid replenishment to deployed units. This situation would be particularly important in a war zone where supply lines can be extended and unreliable.

Weiner5 stated that to implement a successful chemical/biological defense response, the following three questions must be answered: (1) How do we know the outbreak of a disease or malady is a chemical/biological attack and not a natural epidemic? (2) What agents are being used by hostile forces? (3) What countermeasures are available?

The first question proposed by Weiner5 emphasizes the importance of knowing the epidemiology and geographic distribution of chemical agent mimics. This article is intended as a nontechnical introduction to possible chemical warfare mimics, natural and man-made. It is by no means comprehensive, but may serve as a general guide in predeployment planning.

Artificial Mimics of Chemical Warfare Agents

Many of the insecticides used in agriculture, public health, and home pest control are organophosphates, a class of chemicals that includes the nerve agents VX, tabun, and sarin. The signs and symptoms of severe intoxication with these pesticides are very similar, although not identical, to those caused by the warfare agents.6 The primary difference between commercial pesticides and these chemical agents is their levels of toxicity.7 For instance, sarin is approximately 1,000 times more toxic than parathion, one of the most toxic agricultural chemicals. Even so, a severe exposure to high levels of the more toxic agricultural or public health insecticides would be difficult to distinguish from a chemical attack. Exposures to agricultural pesticides could occur simply by traversing a recently treated field. Chemical agent detection systems might indicate chemical warfare agent exposure in such an environment, further complicating the situation. Other potential exposures could occur through ingestion of local insecticide-contaminated food or water. The author once inspected the warehouse of a charitable organization that was inadvertently providing seed corn as part of a food program. The seed corn had obviously been treated with a pesticide to prevent insect and fungal infestations during germination. Ingestion could have caused severe insecticide intoxication. A victim of such a severe exposure may not have time to report the initial effects before losing consciousness7 and, in fact, may not even know of his/her exposure. The similarity in symptoms, combined with uncertainty of how a victim was exposed, would make pesticide poisoning very difficult to distinguish from the intentional use of a chemical agent in an operational environment lacking equipment for definitive chemical analysis.

Many organophosphate insecticides such as parathion, malathion, and chlopyrifos are used in agriculture worldwide. Although significant legal restrictions have been placed on the use of these chemicals in the United States, American laws are not applicable in other countries, therefore pesticides may be in use elsewhere long after they have been removed from American markets.

Many of the newer pyrethroid insecticides are replacing the older acetylcholinesterase inhibitors that include organophosphates and the carbamates. Intoxication with pyrethroids, although perhaps less likely, can cause some of the same symptomatology, causing false alarms. Other pest control products, such as N,N-diethyl metatoluamide repellent may provide falsepositive results when applied to chemical agent detector paper used by U.S. military personnel (D.M. Claborn, unpublished observation).

Because of the potential for false alarms caused by agricultural compounds, predeployment intelligence estimates should include pesticide use in the area of interest. Specific information should include which pesticides are used, which crops are treated, what time of year to expect treatments, and how pesticides are applied. Personnel should be aware of signs that a field has been treated recently (e.g., numerous dead rodents or birds, a wet deposition when surrounding fields are dry, and even warning placards placed at the borders of fields). This knowledge could be useful in preventing false alarms and avoiding hazardous environments.

Natural Mimics of Chemical Nerve Agents

Some animal envenomations cause symptoms similar to those caused by nerve agents. The bite of an elapid, a snake in the same family as the cobras and kraits, can result in heavy salivation, paralysis, muscle tremors, and death. If the victim is unable to communicate, his condition could be attributed to a chemical agent. This scenario is unlikely, but it demonstrates tne potential for confusion caused by animal envenomations. A more likely scenario is provided by sea snakes (family Hydrophiidae). Their venoms contain potent neurotoxins that cause paralysis, respiratory failure, and even death.8 Death occurs when the venom binds to acetylcholine receptors at the neuromuscular junction. Although this is a different toxic mechanism from that of warfare agents that inhibit acetylcholinesterase, similar symptoms are elicited. Complicating matters even further is the fact that the victim may not realize that he/she has been bitten; he/she may not feel the snake attack and the fang punctures may be invisible to the naked eye.

Another well-documented chemical mimic is that of tick paralysis, a condition in which the anesthetic injected by a feeding tick causes progressive numbness and paralysis. If unrecognized, this condition can be rapidly fatal but it is easily cured by removal of the tick. It is characterized by ascending symmetric, flaccid paralysis. Tick paralysis can be confused with Guillain-Barré syndrome, botulism, and myasthenia gravis;9 therefore, these conditions could also be considered chemical and biological mimics by association.

Fortunately, these events would likely occur individually, whereas nerve agents used in warfare or terrorism would probably affect several people and would be accompanied by other observable environmental effects such as bird deaths and fish die-offs. Nevertheless, any person showing signs of nerve disorders, especially on a sparsely populated battlefield, would always be cause for concern.

Mimics of Vesicants

Numerous environmental factors can produce dermatological symptoms similar to those caused by vesicating warfare agents like mustard and Lewisite. In the outbreak of blistering disease in Arizona, diagnostic considerations included contact dermatitis, thermal or chemical burns, impetigo, herpes simplex/zoster, porphyria, pemphigus, dermatitis herpetiformis, and dermatological manifestation of coccidiomycosis.1 This range of possibilities includes everything from physical causes (thermal burns) to communicable disease (coccidiomycosis). Chronic skin conditions must also be considered. Blistering could be something as common as poison ivy or sunburn, both of which could affect several people at once. (Interestingly, a recent event of "chemical warfare" using poison ivy was reported from Haiti, when a group of government supporters attacked a group of protesters with poison-ivy spiked water10). Other conditions such as impetigo or pemphigus, however, would probably be limited in occurrence and would require extensive medical expertise to diagnose.

Several insects and other arthropods are known to cause blisters as discussed earlier. Rove beetle dermatitis has been documented in Tanzania,11 Australia,12 Okinawa,13 Vietnam,14 Egypt,15 Uganda,16 Kenya,17 and Peru.18 In at least one instance, an entire village was evacuated in response to these beetles,12 indicating that symptoms can occur in several persons at once, as would be expected with chemical warfare. Another beetle, the meloid known as the blister beetle, can also cause impressive blistering, although victims usually remember handling the insect before the onset of the blisters.19 This is not true of rove beetles.

Skin irritants have also been documented with millipedes and caterpillars. The urticaria caused by caterpillars would probably not be confused with that caused by a blister agent like mustard, but it could be confused with the symptoms of phosgene oxime, another type of chemical agent. Phosgene oxime is a urticant or nettle agent that causes a corrosive type of skin injury.20 It is not a true vesicant because it does not cause blisters, but it affects the skin, eyes, respiratory system, and gastrointestinal tract. Dermal symptoms include an erythematous ring within 30 s of exposure. An eschar forms in the affected area within 1 week and the skin sloughs off after approximately 3 weeks. Similar symptoms that can be confused with this urticaria can be caused by urticating spines on certain caterpillars. Large-scale urticaria can be induced when caterpillar spines of large populations become airborne and spread over a large area. In one of the largest examples of caterpillarinduced urticaria, 600 of 6,000 soldiers were affected.21,22 The urticarial conditions caused by caterpillars would not be as severe as the symptoms caused by phosgene oxime, but dermatological conditions in multiple victims would certainly cause some concern in a potential chemical warfare environment.

The presence of chemical mimics can obviously cause unwarranted alarm and degrade the war-fighting capacity of a unit. Deployments in environments with a risk of chemical agent exposure are associated with intense fear of chemical warfare.23 Psychologically, the impact of perceived or actual chemical attacks results in casualties from acute stress disorder, grief, anger, scapegoating, and somatization disorders. During the Gulf War, some military personnel exhibited panic, hyperventilation, and an inability to don respirators even when chemical alarms were sounding. Obviously, the threat of exposure to chemical agents, whether real or perceived, has a lasting and adverse impact on human health.

For these reasons, a complete analysis of potential mimics should be part of any predeployment intelligence effort for areas of imminent or existing conflict. Especially important is a thorough knowledge of pesticide use, including type, formulation, crop usage, and targets of the most toxic chemicals. This information could be used by unit commanders not only to help identify false alarms, but also to avoid exposures that might predispose individuals to serious intoxication in the event of a subsequent chemical warfare event. Other information that would be useful would be the types of allergenic plants, "blistering" or urticating insects, and naturally occurring disease that might cause concern. Great care would be needed in using this information. A delay in diagnosis could be fatal to victims of a chemical attack and any suspect case would need to be treated appropriately. However, proper assessment of mimics could prevent dangerous misdiagnoses and improper treatment. Perhaps as importantly, it could prevent the unnecessary use of limited chemical protective postures in environments where this would be detrimental to unit effectiveness and individual health. In addition, a postdeployment assessment of mimics could allay fears of exposure to warfare agents.

A similar situation exists with the biological agents that also have numerous mimics. Natural occurrences of diseases such as anthrax and plague may be confused with intentional outbreaks caused by weaponized strains of the same agents. Also, diseases that are similar in presentation such as monkey pox and smallpox may be confused. This article is not intended to address biological agents that are thoroughly reviewed elsewhere.24-26

Currently, acquisition of information on chemical warfare mimics is not standardized or codified. However, the Navy Disease Vector Ecology and Control Centers in Jacksonville, Florida, and Bangor, Washington, are working jointly to acquire certain parts of this information as part of other programs. The mission of these centers includes acquiring information on the risk of vector-borne disease throughout the world. An important part of this information is the types of agricultural pesticides used in areas of strategic interest. Because many disease vectors develop resistance to insecticides through incidental and long-term exposure to agricultural insecticides, information on the local use of insecticides suggests the resistance status of local vectors. This information, in turn, drives decision making on what vector control measures are appropriate for troops deploying to a given area. Although the initial purpose for gathering this information is independent of chemical warfare mimics, it can be used to identify false alarm risks by identifying potential chemical mimics and geographical areas where such mimics are common. Some of the other mimics are identified as medical risks in the country-specific literature disseminated by the Armed Forces Pest Management Board, the Armed Forces Medical Information Center, and the Defense Pest Management Information Analysis Center.

This type of information is most useful when it is available to the troops at risk for exposure to chemical warfare agents and mimics of chemical agents. Specifically, this and other preventive medicine information can aid the line officer and others responsible for troops in the field. Differential diagnosis of potential chemical agent symptoms and the mimics that may cause confusion should be presented at any advanced course on chemical warfare agents, whether for medical or nonmedical audiences. Proper identification of environmental mimics can prevent unnecessary alarm and injuries, and reduce waste of expensive chemical protective gear. However, this information must always be accompanied by a strong emphasis on proper treatment and first-aid for any suspected victim.

Acknowledgments

I thank CDR Kenneth Stein, MSC USNR, CDR Harvey Adkinson, MSC USN, Dr. Andrew Beck, and CDR Joseph Conlon, MSC USN (Ret.), for their efforts in reviewing this article and contributing ideas.

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Guarantor: CDR David M. Claborn, MSC USN

Contributor: CDR David M. Claborn, MSC USN

Navy Disease Vector Ecology and Control Center, Naval Air Station, Box 43, Jacksonville, FL 32212-0043.

This manuscript was received for review in August 2003. The revised manuscript was accepted for publication in January 2004.

Copyright Association of Military Surgeons of the United States Dec 2004
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