Biological terrorism and veterinary medicine in the United States


Journal of the American Veterinary Medical Association September 1, 2000


David A. Ashford, DVM, MPH, DSc; Thomas M. Gomez, DVM, MS; Donald L. Noah, DVM, MPH; Dana P. Scott, DVM; David R. Franz, DVM, PhD

From the United States Department of Health and Human Services, Centers for Disease Control and Prevention, Atlanta, GA 30333 (Ashford); USDA, Animal and Plant Health Inspection Service, Atlanta, GA 30333 (Gomez); United States Air Force, 902 Seminole Rd, Frederick, MD 21701 (Noah); United States Armed Forces Institute of Pathology, Washington, DC 21701 (Scott); and the Southern Research Institute, Frederick, MD 21701 (Franz).


Although recent reports have emphasized the need for improving the ability to detect a biological terrorist attack on human populations,1,2 the use of veterinary services in this effort and the potential for the targeting of livestock (eg, horses, cattle, sheep, goats, swine, and poultry) have been addressed only briefly. Improving surveillance for biological terrorist attacks that target livestock and improving detection and reporting of livestock, pet, and wild animal morbidity and mortality are important components of preparedness for a covert biological terrorist attack. Although veterinarians have been mentioned as an integral part of biological terrorism preparedness planning, the importance of improving surveillance among livestock, pet, and wild animal populations has not been emphasized. Any improvement in detection of a covert biological terrorist attack should be a goal of human and veterinary health programs. Although a system for detecting and reporting nonendemic or foreign animal diseases exists in the United States, the system needs strengthening to increase the likelihood of detecting a covert biological terrorist attack on humans or other mammals. Following a covert bioterrorist attack with an agent targeting livestock or human populations, the front line of practicing human and veterinary healthcare providers will be essential for detection, reporting, and response.

Biological Warfare

Biological warfare may be defined as the intentional use of microorganisms or toxins derived from living organisms to cause death or disease in humans, other animals, or plants as part of war. For more than 50 years, world powers have developed biological weapons and countermeasures to biological weapons. Early programs in World War I included targeting livestock. During World War I, the US and German programs included contamination of feed and livestock for export.3 Burkholderia mallei was allegedly used in the German program to infect horses and mules in Mesopotamia and France, and Allied forces lost more than 200 mules to Bacillus anthracis and B mallei between 1917 and 1918.3,4 Targeting animals continued to be a strategy of offensive programs throughout World War II.5 After President Nixon discontinued US offensive biological research,6 a multilateral agreement to halt offensive biological warfare programs, the Biological and Toxin Weapons Convention, was ratified in 1975. However, ratification of this convention did not end the threat of biological weapon attacks. After the apparent demise of the Soviet offensive program, biological threats have increased in the form of biological terrorism.

Biological Terrorism

Biological terrorism may be defined as the intentional use of microorganisms or toxins derived from living organisms to cause death or disease in humans, other animals, or plants in civilian settings. During the past decade, the threat of biological terrorist activities has increased, and the first instances of biological terrorism ever reported occurred in Japan and the United States.3,7,8 Also, during the same period, there has been an increase in domestic and international conventional (nonbiological) terrorism. For the first time in history, international terrorists were successful in causing a large-scale attack on US civilians in 1989 with the World Trade Center bombing in New York City. In 1994, domestic terrorism occurred with the bombing of the United States Federal Building in Oklahoma City. In 1984, in The Dalles, Oregon, a local terrorist organization poisoned a salad bar with Salmonella spp, resulting in 751 infections and hospitalization of 45 people.7 The number of bombings and other attacks on US embassies has increased throughout the world. In 1995, the Japanese terrorist organization Aum Shinrikyo attacked Tokyo subways with sarin gas, killing 23 people and hospitalizing more than 400. Aum Shinrikyo also attempted the release of biological agents in Tokyo subways. During the past 4 years, on 3 occasions in the United States, attempts by extremist organizations to purchase potential biological weapons have been thwarted, leading us to wonder how many attempts were successful. Recently, the number of incidents of threatened use of B anthracis has been increasing.8 In the face of this increased threat, the executive and legislative branches of the US government have passed a series of acts aimed at improving preparedness for the possibility of a biological terrorist attack against US citizens.9

Terrorist use of biological weapons may be overt or covert, depending on the motivations of the perpetrators. In the national effort to prepare plans and improve capacities for preparedness and response to a possible biological terrorist attack, one fundamental concern has been the nation's ability to detect a covert attack and differentiate it from a natural disease occurrence. In the absence of an explosion or other indication of an attack, the front-line providers of human and veterinary medical care (as opposed to law-enforcement or emergency response staff who typically would respond to an announced attack or threat of attack) will be critical to early detection and reporting of an unannounced biological terrorist attack. A covert attack could develop as a small or large increase in morbidity and mortality among human or livestock populations or both. Whether livestock or humans or both will be affected will depend on the pathogen that is released. Because animal disease outbreaks have the potential to wreak economic havoc on US agriculture, we must assume that livestock are an attractive target to potential terrorists. Therefore, every outbreak of unusual illness should be suspected as a possible intentional attack on humans or livestock, until investigated thoroughly. Such outbreaks may include confirmation of unusual diseases or an abrupt increase in commonly observed signs, without a firm diagnosis. In covert attacks, speed of detection and reporting of a suspicious event will determine the timeliness and effectiveness of the response. In turn, the timeliness and effectiveness of response will define the ability to reduce morbidity and mortality. Attacks aimed at US livestock populations could adversely impact our food security (safety, affordability, quality, and abundance), challenge our response capacity, and be economically devastating by limiting or eliminating international and domestic trade. Also, if the biological agent is zoonotic, public health will be affected.

Biological Agents

Offensive biological warfare programs, which form the basis for assessing agents used for biological terrorism, traditionally have selected human pathogens on the basis of physical and biological characteristics that maximize their utility as weapons. Important characteristics include pathogenicity or toxicity, ease of production and use as a weapon, and stability. Because bacteria, viruses, and toxins are neither volatile nor traumatic to the skin, agents were selected that could be delivered as respirable aerosols (1- to 20-m particles). Years of research by several nations resulted in essentially the same list of microbial agents.6,9 Some of these agents, if properly prepared and delivered under ideal meteorologic conditions, could infect unsuspecting humans and livestock, causing disease or death of thousands within days or weeks.10,11 Of these agents, B anthracis, Yersinia pestis, Francisella tularensis, Brucella spp, B mallei, Coxiella burnetii, Venezuelan equine encephalomyelitis virus, other arboviruses, and viral hemorrhagic fever viruses may result in casualties among humans, livestock, or pets.

In addition to these biological warfare agents that potentially could affect domestic animals and humans, the list of potential bioterrorist agents for livestock should include the foreign animal diseases, some of which are zoonotic diseases (Appendix). Most of these diseases have been eradicated from livestock populations in the United States, and vaccines for them are no longer used routinely. Thus, having no existing herd or flock immunity, domestic livestock populations are vulnerable. Modern high-density vertically integrated industries, livestock sale and transportation practices, and centralized feed supply and distribution systems only add to the potential for animal-to-animal or fomite transmission. The foot-and-mouth disease outbreak that occurred in the swine population of Taiwan in 1997 revealed the extreme vulnerability of such an industry to contagious disease transmission.12,13 Islandwide, more than 6,150 outbreaks caused almost total depopulation of swine and resulted in an overall economic loss that included 50,000 jobs and 0.5% of that nation's gross domestic product.

Animal Vulnerability

Although biological agents have been used against military animals, and weapons have been developed against domestic animals in the past, counter-terrorism planning has paid little attention to the vulnerability of our animal populations.14,15 The agents selected historically for use against animals, like those designed for human targets, were not highly contagious. They were intended to be delivered in animal feed or by injection. However, new biological weapons may include foreign animal disease agents that may be naturally occurring and are highly infectious or contagious, have potential to cause severe morbidity or mortality, are easy to produce or deliver, or are potential zoonoses. These include the viral agents of Newcastle disease, foot and mouth disease, classical swine fever (hog cholera), highly pathogenic avian influenza, African swine fever, Venezuelan equine encephalomyelitis, and Rift Valley fever. Additional agents of concern, some of which are endemic in the United States, include pseudorabies virus, B anthracis, botulinum toxin, B mallei, F tularensis, and Brucella spp. Attacks using noncontagious respirable aerosol agents, one of the possibilities for an attack on humans, may not be selected by terrorists targeting animal populations. Thus, aerosol attack with anthrax, for example, one of the most feared threats to humans, may not be the first choice for attack against the US livestock industry. The impact of such an attack, even on one of our largest feedlots, would probably not justify the technical requirements of production, preparation as a weapon, and delivery. However, the small-scale release of one of several highly contagious agents in a single feedlot would be extremely effective and would disrupt our economy and society. Furthermore, terrorists may use a combination of these agents, attack in more than one location simultaneously, use artificial methods of disease dispersion that create unusual clinical characteristics, or use drug-resistant or genetically modified organisms.

Surveillance and Reporting System

The surveillance and reporting system for biological agents used against humans and domestic animals should include several stages. For example, after a covert attack with a contagious viral agent at large points of sale or transportation, local producers may observe an unusual pattern of disease in their herds. Initial nonspecific signs may be misinterpreted as representing the onset of a large outbreak of an endemic disease. Only later will subsequent signs suggest a foreign animal disease. Local veterinarians, although academically familiar with the foreign animal disease list, are rarely familiar with the many possible signs of these diseases. These veterinarians, however, are the front line of our animal disease surveillance system. Veterinarians accredited by the USDA to perform certain activities such as issuing health certificates must complete an examination that includes information concerning foreign animal diseases. However, continuing education presently is not mandatory for maintenance of this certification, and experience with these diseases is rare. It is important that these practitioners be in a high state of readiness for recognition and response to a suspected foreign animal disease outbreak.

Local accredited veterinarians must immediately report unusual signs of disease or signs consistent with a foreign animal disease to the appropriate state animal health officials. However, it should be reemphasized that reporting must be accomplished as early in the disease process as possible and will be based on clinical suspicion alone. Early reporting will permit immediate responses by state and federal animal health officials, which include field investigations by trained foreign animal disease diagnosticians and reference laboratory support via the USDA, Animal and Plant Health Inspection Service, Veterinary Services, National Veterinary Services Laboratories. Suspicion of intentional introduction of a foreign animal disease that is considered credible by animal health officials must be reported to the Federal Bureau of Investigation (FBI). By Presidential Decision Directive 39, United States Policy on Counter Terrorism, the FBI is the coordinating agency for all biological terrorist threats or attacks.

Epidemiologic Investigation

Epidemiologic investigation of a covert attack would differ little from that conducted following a naturally occurring outbreak of a foreign animal disease, because features of a manmade outbreak may differ little from those of a naturally occurring outbreak. Such an investigation includes identification of the increase in morbidity and mortality that causes suspicion of a possible biological attack, report of any suspicion to animal health authorities, confirmation of disease diagnosis and identification of the biological agent, development of a case definition, identification of exposed or potentially exposed animals or herds, control of animal and vehicle movement in the affected areas, depopulation or vaccination of appropriate animals or herds, and, throughout the process, informing and educating all appropriate persons, including the public. Credible, informed professionals who can articulate the threat to humans and domestic animals with candor and accuracy will be vital to success of the response. Failure to effectively accomplish this aspect of the mission will only worsen the situation and facilitate achievement of terrorist goals.

In the United States, a basic system is in place to detect and respond to terrorism that involves foreign animal diseases.16 We have veterinary practitioners, state and federal veterinarians, state and federal reference laboratories, and foreign animal disease experts within civilian and military veterinary response teams. However, in recent years, animal industry groups and state animal health officials have been concerned about the nation's ability to respond to an emergency. Each level of the existing system requires reinforcement. In a collaborative effort with industry groups, other federal and state agencies, academia, veterinary diagnostic laboratories, and other animal health organizations, the USDA (Animal and Plant Health Inspection Service, Agricultural Research Service, Food Safety and Inspection Service, and Office of the Inspector General) is in the process of reinforcing and strengthening US infrastructure and ability to effectively prepare for, prevent, respond to, and recover from an animal health emergency.16 As part of this effort, we must invest resources (personnel and funds) and commitment in certain areas. We must monitor disease patterns via effective surveillance and herd health programs; teach and practice preventive medicine; educate veterinary clinicians, the public, producers, policy-makers, and industry leaders regarding the threat and agents of concern; develop emergency plans that include communication and diagnostic strategies; develop and conduct relevant training including field exercises or simulations; develop better coordinated intelligence capabilities and systems; strengthen our research and diagnostic reference laboratory capability; and strengthen partnerships with federal and state emergency management agencies, industry, and other animal health and public health organizations.

References

  1. Noah DL, Sobel AL, Ostroff SM, et al. Biological warfare training: infectious disease outbreak differentiation criteria. Mil Med 1998;163:198–201.
  2. Kadlec RP, Zelicoff AP, Vrtis AM. Biological weapons control. Prospects and implications for the future. JAMA 1997;278:351–356.
  3. Christopher G, Cieslak TJ, Pavlin J, et al. Biological warfare. A historical perspective. JAMA 1997;278:412–417.
  4. Robertson AG, Robertson LJ. From asps to allegations: biological warfare in history. Mil Med 1995;160:369–373.
  5. Harris S. Japanese biological warfare research on humans: a case study of microbiology and ethics. Ann NY Acad Sci1992;666:21–52.
  6. 6. Massachusetts Institute of Technology, Lincoln Laboratory. A relative assessment of putative biological-warfare agents. Technical Report 1040. Cambridge, Mass: Massachusetts Institute of Technology, 1997;17.
  7. Torok TJ, Tauxe RV, Wise RP, et al. A large community outbreak of salmonellosis caused by intentional contamination of restaurant salad bars. JAMA 1997;278:389–395.
  8. Centers for Disease Control and Prevention. Bioterrorism alleging use of anthrax and interim guidelines for management–United States, 1998. MMWR Morb Mortal Wkly Rep 1999;48:69–74.
  9. Ferguson JR. Biological weapons and US law. JAMA 1997;278:357–360.
  10. Franz DR, Jahrling PB, Friedlander AM, et al. Clinical recognition and management of patients exposed to biological warfare agents. JAMA 1997;278:399–411.
  11. World Health Organization. Health aspects of chemical and biological weapons: report of a WHO group of consultants. Geneva, Switzerland: World Health Organization, 1970.
  12. Dunn CS, Donaldson AI. Foot-and-mouth disease in Taiwan. Vet Rec 1997;140:407.
  13. Dunn CS, Donaldson AI. Natural adaptation to pigs of a Taiwanese isolate of foot-and-mouth disease virus. Vet Rec 1997;141:174–175.
  14. Poupard JA, Miller LA. History of biological warfare: catapults to capsomeres. Ann NY Acad Sci 1992;666:9–20.
  15. Harris R, Paxman J. A higher form of killing: the secret story of chemical and biological warfare. New York: Hill & Wang, 1982;97–100.
  16. Bowman QP, Arnoldi JM. Management of animal health emergencies in North America: prevention, preparedness, response and recovery. Rev Sci Tech 1999;18:76–103.
  17. United States Animal Health Association. Foreign animal diseases. Pat Campbell & Associates, 1998.

Appendix

International Office of Epizootics (OIE) list-A diseases.17 The OIE list-A diseases are transmissible diseases with potential for widespread and rapid transmission, irrespective of national borders, that are of serious socioeconomic or public health consequence and of major importance in the international trade of animals and animal products.

Foot-and-mouth disease—Foot-and-mouth disease virus is a picornavirus of the genus Apthovirus, with at least 60 subtypes within 7 serotypes. The virus is highly contagious in cloven-hoofed domestic (cattle, pigs, sheep, goats, and water buffalo) and wild animals. The disease is characterized by fever and vesicles with subsequent erosions in the oral cavity, nares, muzzle, feet, or teats.

Vesicular stomatitis—Vesicular stomatitis is caused by an arbovirus with 2 serotypes (New Jersey and Indiana). The disease is characterized by fever, vesicles, and subsequent erosions in the oral cavity, teats, and feet. Horses, cattle, and pigs are susceptible; sheep and goats are rarely affected.

Swine vesicular disease—Swine vesicular disease virus is classified in the family Picornaviridae, genus Enterovirus. Pigs are the only natural host; disease is characterized by fever and vesicles with subsequent erosions in the oral cavity and on the snout, feet, and teats.

Rinderpest—Rinderpest virus is in the family Paramyxoviridae, genus Morbillivirus, and causes contagious disease in cattle, domestic buffalo, and some species of wildlife, characterized by fever, oral erosions, diarrhea, lymphoid necrosis, and high mortality.

Peste des petits ruminants—Peste des petits ruminants is caused by a Paramyxovirus of the Morbillivirus genus. It is an acute or subacute disease of goats and sheep characterized by fever, erosive stomatitis, conjunctivitis, gastroenteritis, and pneumonia. Goats are usually more severely affected than sheep.

Contagious bovine pleuropneumonia—Contagious bovine pleuropneumonia is a highly infectious acute, subacute, or chronic disease of cattle and buffalo, caused by Mycoplasma mycoides subspecies mycoides. It affects the lungs and, in some instances, the joints.

Lumpy skin disease—Lumpy skin disease of cattle is caused by a virus in the family Poxviridae, genus Capripoxvirus, and is characterized by acute to chronic generalized dermatitis with nodules that may have an inverted conical area of necrosis, lymphadenitis, and persistent fever.

Rift Valley fever—Rift valley fever, caused by a virus in the family Bunyaviridae, genus Phlebovirus, is an arthropod-borne acute febrile disease of sheep, cattle, and goats, characterized by abortion, high mortality in young animals, and hepatic necrosis.

 

Bluetongue—Bluetongue, caused by an orbivirus in the family Reoviridae, is an acute or subacute insect-borne disease of certain susceptible ruminants.

Sheep pox and goat pox—The causative agent of sheep and goat pox is a Capripoxvirus that causes acute to chronic disease characterized by generalized pox lesions throughout the skin and mucous membranes, persistent fever, lymphadenitis, and pneumonia.

African horse sickness—African horse sickness is caused by an Orbivirus and is a highly fatal, viscerotropic, insect-borne disease of horses and mules that generally causes subclinical disease in other Equidae. Clinical signs and lesions in the respiratory and circulatory systems result from increased vascular permeability.

African swine fever—African swine fever virus is a DNA virus that has not yet been classified and has the characteristics of an Iridovirus and a Poxvirus. African swine fever is a tick-borne contagious febrile systemic disease of swine.

Classic swine fever—The causative agent of classic swine fever (hog cholera) is in the Pestivirus group of the family Flaviviridae. Classic swine fever is a highly contagious disease of swine that occurs in acute, subacute, or chronic forms. In the acute form, the disease is characterized by high fever, signs of severe depression, multiple superficial and internal hemorrhages, and high morbidity and mortality.

Highly pathogenic avian influenza—Avian influenza is caused by a type A virus (subtypes H5 and H7) in the family Orthomyxoviridae, which also infects humans, swine, horses, and other mammals.

Newcastle disease—The Newcastle disease virus belongs to the Paramyxoviridae family and has 3 types (lentogenic, mesogenic, and velogenic) that reflect increasing degrees of virulence. Velogenic Newcastle disease in chickens is characterized by lesions in the brain or gastrointestinal tract, morbidity rate near 100%, and mortality rate as great as 90%. Clinical signs include neurologic signs or severe signs of depression.