Handbook on Biological Warfare Preparedness

Handbook on Biological Warfare Preparedness provides detailed information on biological warfare agents and their mode of transmission and spread. In addition, it explains methods of detection and medical countermeasures, including vaccine and post-exposure therapeutics, with specific sections detailing diseases, their transmission, clinical signs and symptoms, diagnosis, treatment, vaccines, prevention and management. This book is useful reading for researchers and advanced students in toxicology, but it will also prove helpful for medical students, civil administration, medical doctors, first responders and security forces.

As the highly unpredictable nature of any event involving biological warfare agents has given rise to the need for the rapid development of accurate detection systems, this book is a timely resource on the topic.

• Introduces different bacterial and viral agents, including Ebola and other emerging threats and toxins
• Discusses medical countermeasures, including vaccines and post-exposure therapeutics
• Includes a comprehensive review of current methods of detection

• Language: English
• Publisher: Academic Press
• Release date: Oct 5, 2019
• ISBN: 9780128120552

Book preview

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Chapter 1

Biological warfare agents: History and modern-day relevance

S.J.S. Flora    National Institute of Pharmaceutical Education and Research-Raebareli, Lucknow, India

Abstract

Since ancient times, the use of hazardous materials, bacteria, viruses, and toxins as weapons at some stages in war has been well documented. These agents can cause large numbers of causalities both to the military as well as civilian populations and are difficult to manage. Chlorine was first used as a chemical weapon during World War I in 1915 by German military forces at Ypres, Belgium. Military use of chemical and biological warfare agents in time of war demonstrated their level of toxic effect on living beings, i.e., they lead to mass destruction, and occasions where these toxic agents had been used against civilians by terrorists highlighted that these agents could be a danger to whole world community. Preparedness against biological agents prompted research about the type of diseases caused by them, trained persons who can tackle the situation at the time of incidence, better diagnostic tools, and improved public health systems. The menace that occurs due to the use of these agents in war or terrorism can be lessened with the accessibility of better detection technologies. This chapter gives insight about the history of biological warfare agents, classification of biological warfare agents, and also the detection systems available/in process of development to detect them.

Keywords

Biological warfare agents; Anthrax; Classification; Preparedness; Detection

History of biological warfare agents

Infectious diseases and war are always interlinked. Even without a precise understanding of how diseases were spread, it was understood early that dead animals or humans could cause disease. There are some accounts of biological warfare in the form of poison on arrows, and polluting wells and other source of water by opposing armies. However, apart from some rare well-documented events (Eitzen and Takafuji, 1997) it is often very difficult for historians and microbiologists to understand natural epidemics from alleged biological attacks, because little information is available for times before the advent of modern microbiology and the passage of time may also have distorted the reality of the past. Evidence from Persian, Greek, and Roman literature suggests the use of animal cadavers to contaminate wells and other sources of water around 300 BC, and in 400 BC, Scythian archers infecting their arrows by dipping them in decomposing bodies or in blood mixed with manure. In 190 BC during the Battle of Eurymed, Hannibal won a naval victory over King Eumenes II of Pergamon by firing earthen vessels full of venomous snakes onto the enemy ships. In the 12th century AD, during the battle of Tortona, Barbarossa used the bodies of dead soldiers to poison wells. During the siege of Caffa, a well-fortified Genoese-controlled seaport (now Feodosia, Ukraine), in 1346, the attacking Tartar force experienced an epidemic of plague (Wheelis, 2002). The Tartars threw the cadavers of their deceased into the city, and it is believed that this has initiated a plague epidemic in the city. The outbreak of plague forced the retreat of the Genoese forces. The plague pandemic known as the Black Death spread throughout Europe, the Near East, and North Africa in the 14th century and was probably the most devastating public health disaster in recorded history. The ultimate origin of the plague remains uncertain: several countries in the Far East, China, Mongolia, India, and Central Asia have reported these instances in the past (Rauw, 2012). The biological warfare attack in Caffa is one of the terrible consequences in history when diseases were used as weapons.

During the battle between Russian and Swedish forces at Reval in Estonia in 1710, catapulted plague cadavers were used. In the 18th century, during the French and Indian War, British forces in North America gave blankets from smallpox patients to the Native Americans to transmit the disease to the immunologically naïve tribes. In 1863, a Confederate surgeon was arrested and charged with attempting to import yellow fever-infected clothes into northern parts of the United States during the Civil War (Hunsicker, 2006). Biological warfare became more sophisticated against both animals and humans during the 1900s. The conception of Koch’s postulates and the development of modern microbiology during the 19th century made possible the isolation and production of stocks of specific pathogens (Robertson and Robertson, 1995). During World War I (WWI), some reports have suggested that the Germans developed horses and cattle inoculated with disease-producing bacteria, such as Bacillus anthracis (anthrax) and Pseudomonas pseudomallei (glanders), and shipped them to the United States, Russia, and other countries (Hugh-Jones); although Germany denied these reports. In 1924, a subcommittee of the Temporary Mixed Commission of the League of Nations found no hard evidence that bacteriological weapons had been employed in war. On June 17, 1925, the Protocol for the Prohibition of the Use in War of Asphyxiating, Poisonous or Other Gases and of Bacteriological Methods of Warfare, commonly called the Geneva Protocol of 1925, was signed. Because viruses were not differentiated from bacteria at that time, they were not specifically mentioned in the protocol. A total of 108 nations, including the five permanent members of the United Nations (UN) Security Council, eventually signed the agreement. However, the Geneva Protocol did not address verification or compliance, making it a toothless and less meaningful document. Several countries that were parties to the Geneva Protocol of 1925 began to develop biological weapons soon after its ratification. These countries included Belgium, Canada, France, Great Britain, Italy, the Netherlands, Poland, Japan, and the Soviet Union. The United States did not ratify the Geneva Protocol until 1975 (Riedel, 2004).

Biological agents to cause destruction have been used since 6th century BC, wherein it was the poisoning of wells and water supplies that was most common. The very first deliberate act of spreading disease occurred in 1346 at the Siege of Caffa (Feodosia, Ukraine), when a Tartar army disposed its plague-ridden dead over the walls of the besieged city (Wheelis, 2002). Later, in 1763, during the French and Indian war, an English general intentionally distributed blankets contaminated with small pox scabs to the Native Americans loyal to the French, which caused a huge epidemic to kill the tribal people. The Germans also has their own bioweapon program for WWI, in which they purposely infected horses and other transport animals with disease causing microbes of anthrax and glanders (Frischknecht, 2003). After WWI, the Geneva Protocol was signed banning biological weapons, which all countries in attendance signed except Japan.

Before the start of WWII, the Japanese produced bioweapons agents to cause anthrax, plaque, cholera, and shigellosis, for which field experiments were done on Chinese prisoners of war and civilians, which led to several thousand deaths (Barras and Greub, 2014). One such experiment included the use of ceramic bomblets containing plague-infected fleas and grain on Chinese cities including Nanking, which attracted rats bitten by fleas contaminated with plague causing microorganisms. When reports were spread about Japan’s bioweapons program, a research program was launched by President Roosevelt on biological agents in 1941. George W. Merck of Merck Pharmaceuticals was named head of the Army’s Chemical Warfare Service, and Camp Detrick, Frederick, MD, was developed into a site for biological weapons research and development.

In 1946, the US officially announced its participation in research related to bioweapons. In 1969, the World Health Organization issued a report that described the volatility of biological weapons, on the basis of which, later that year, President Nixon shut down the US offensive biological warfare program and limited biological weapons research to defensive purposes only (Frischknecht, 2003). In 1972, the Biological Weapons Convention Treaty, which called for all countries to destroy their stocks of bioweapons, was signed by 103 nations including the former Soviet Union (Riedel, 2004). Laboratory acquired small pox infections made the WHO recommend merging all the variola virus stocks, which had to be maintained only by United States and Russia (McFadden, 2010). In 1979, Bacillus anthracis spores were accidentally released at a bioweapons research facility in Sverdlovsk, Union of Soviet Socialist Republics (USSR), which resulted in 68 deaths due to inhalational of anthrax. In the fall of 2001, the US experienced bioterrorism when the members of the Rajneesh cult in Oregon experimented with various bioweapon prior to their 1984 act of bioterrorism. Seeking to influence the outcome of upcoming municipal elections, the cult deliberately contaminated salad bars of local restaurants with Salmonella typhimurium, which caused illness in over 700 people.

In 1992 in Minnesota, the Members of Minnesota Patriots Council, a militia group, planned to kill local authorities with ricin, a potent toxin obtained from castor beans. Another bioterrorism act occurred in the fall of 2001, when Bacillus anthracis spores were placed in at least seven envelopes passing through US mail facilities in Florida, Washington DC, New York, and New Jersey, leading to 22 confirmed and suspected cases of anthrax, of which five were fatal. Table 1 summarizes the historical incidences of biological warfare.

Table 1

Biological warfare agents

Biological warfare agents (BWAs) may be defined as a class of living biological agents used with an intention of creating a state of war by causing disease to humans, plants, and animals. It is used to kill or harm other life forms. Biological agents include infectious agents such as bacteria, viruses, fungi, and insects. In the main, chemical and microorganism toxins are used as warfare agents. These represent two of the three forms of weapons mass destruction: chemical, biological, and nuclear. A chemical weapon uses chemicals to kill living organisms; biological weapons make use of living organisms to kill; whereas nuclear weapons are atomic and hydrogen bombs with explosive yields. Biological weapons are one of the most researched and used ways of causing havoc. They can be delivered in various ways, such as through the air by aerosol sprays, which disperse in the air to cause illness in the respiratory tract. They can also be delivered in the form of explosives, and through food and water by contaminating bodies of water with large amounts of disease causing organisms. A biological warfare attack can be defined at a situation when a large number of people are detected with uncommon symptoms, dead animals with uneven medical findings. Protective measures should be used against bioweapons such as the high-efficiency particulate air (HEPA) filter masks used for tuberculosis exposure, which filter out most biological warfare particles delivered through the air, and providing antibiotic treatment for immunization of officials.

Characteristics of biological weapons

Major classes of living organisms that infect living hosts may depend upon the interactions between the host and the biological agent. These interactions may depend upon the individual, e.g., immune response, and nutritional and health status, and the environmental conditions to which the host is exposed, such as sanitation, water quality, etc. (Rauw, 2012). Some of the important characteristic features by which they can be classified are as follows (Table 2):

1.Virulence: The relative disease causing ability of a microorganism, which may differ from species to species.

2.Infectivity: The ability of the agent to enter, survive, and multiply inside the host, and what rate of infection it causes.

3.Incubation period: The time span between first exposure of infective agent and the first appearance of symptoms in the host body.

4.Lethality: The death causing ability of an organism. It varies from organism to organism and the virulence factor present in them.

5.Mode of transmission: How an organism can be transferred in the environment: by vector or without vector.

Table 2

Advantages and disadvantages of biological agents

Use of biological warfare agents has both positive and negative aspects, as stated below in Table 3. As an advantage, the agents should be easier and simple to produce, so that minimum time is required for production. Cost effectiveness is another important aspect that should be taken into account when developing a warfare agent. The agent should be a potent killer, able to cause mass destruction with very high transmission rate, and have no available treatment (Thavaselvam and Vijayaraghavan, 2010). The disadvantages of these agents include the difficulty in delivery and problems in protecting the workers from the agents.

Table 3

Characteristics of an ideal biological warfare agent

In order to consider a biological warfare agent as an ideal one, it should possess the following important features (Fig. 1). It should be cost effective, should harm the maximum individuals, and should target the maximum number of hosts. Its delivery should be easy and should be aerosolized.

Fig. 1 Characteristics of an ideal biological warfare agent.

Classification of biological warfare agents according to the Center for Disease Control

According to the Centers for Disease Control and Prevention, Atlanta, United States (CDC) the Biological agents can be classified into A, B, and C, on the basis of priority from highest to lowest based on their virulence rate and rate of transmission, as shown in Fig. 2 (Sofaer et al., 1999; Perry, 2006).

Fig. 2 Classification of biological agents according to CDC.

Present-day relevance of the agents

Since the 1980s, bioterrorism has been a very common problem. Several countries have been offensive in using these biological weapons. In 1985, Iraq used anthrax, botulinum toxin, and aflatoxin in the Persian Gulf War (Zilinskas, 1997). Another incidence of biowar seen in the recent past was the incident in 1984 wherein followers of the Bhagwan Shree Rajneesh contaminated restaurant salad bars in Oregon with Salmonella, which infected around 750 people. Another incidence was in 1993, where a Japanese sect of the Aum Shinrikyo cult attempted an aerosolized release of anthrax from building tops in Tokyo (Takahashi et al., 2004). In 1986, Tamil guerrillas operating in Sri Lanka poisoned tea with potassium cyanide in an effort to cripple the Sri Lankan tea export industry. In 1993, Iran allegedly deliberately contaminated the water supplies of the forces from United States and Europe to contaminate the water of Galilee with an unspecified biological agent (Sofaer et al., 1999). Two members of the Minnesota Militia group, in 1995, were found to possess ricin for revenge against local government officials (Johnson, 2012). In 1996, an Ohio man attempted to obtain bubonic plague cultures through the mail (Mishra and Trikamji, 2014). Later, in 2001, anthrax was delivered by mail to US media and government offices resulting in five deaths. In 2002, terrorists were arrested in Manchester, England, for the production of ricin with the plan to attack the Russian embassy with the toxin (Mishra and Trikamji, 2014).

Detection

Biological agents that can be used during war and for terrorism should be detected accurately and reliably so that damage and further spread of these agents can be controlled. The challenge in the development of detection systems is to make instruments or methods sensitive enough to detect the concentration at which microorganism can cause disease in humans, and also confirm the presence of these agents in varied matrices. Other than this, detection system should be portable, user friendly, and able to be utilized for the detection of multiple agents. The various types of sample, such as human clinical samples like blood, sputum, urine, stool, cerebrospinal fluid, powdery material, food, air, and water samples need to be examined. There are various detection protocols, for instance, biochemical test based assays, antibody based assays, and nucleic acid based assay, with limited range of scale that can be successfully use at the time of an emergency situation (Thavaselvam and Vijayaraghavan, 2010). BWAs are difficult to detect in real time because they can produce disease at very low concentrations and can be embedded in the naturally occurring environment. These agents can be detected by extensive analysis and when they cause disease in a host. The conventional diagnostic test (double layer agar and polymerase chain reaction) and analytical laboratory methods, such as high performance liquid chromatography or enzyme linked immunosorbent assay, have some drawbacks. Therefore, the development of methods and systems to detect BWAs in real time is urgently