Lecture 16 - Bioterrorism PDF

Bioterrorism ▪ Rivka H. Borger, PA ▪ Touro College ▪ Microbiology ▪ Summer 2021 Bioterrorism ▪ Bioterrorism - a form of terrorism where there is the intentional release of biological agents such as bacteria, viruses, or other mi...

Bioterrorism ▪ Rivka H. Borger, PA ▪ Touro College ▪ Microbiology ▪ Summer 2021 Bioterrorism ▪ Bioterrorism - a form of terrorism where there is the intentional release of biological agents such as bacteria, viruses, or other microorganisms. This can also be referred to as germ warfare. Bioterrorism ▪ Biological agents are organisms or toxins that can kill, harm, or disable people, animals, and plants. ▪ Biological warfare is the deliberate release of germs or other biological substances that can deliberately cause illness. Biological Warfare ▪ There are three basic groups of biological agents that could likely be used as weapons: bacteria, viruses and toxins. ▪ Biological agents can be spread by spraying them into the air, through person-to-person contact, infecting animals which carry the disease to humans, and contaminating food and water. History of Bioterrorism and Biological Warfare sdde ▪ Infectious diseases were recognized for their effect on people and armies as early as 600 BCE. ▪ The use of filth and cadavers, animal carcasses, and contagion had devastating effects and weakened the enemy. ▪ Polluting wells and other sources of water of the opposing army was a common strategy that continued to be used through the many European wars, during the American Civil War, and even into the 20th century.  History of Bioterrorism and Biological Warfare ▪ 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. ▪ The Tartars, however, used this opportunity to throw the cadavers of their deceased into the city, thus initiating a plague epidemic in the city. ▪ The outbreak of plague followed, forcing a retreat of the Genoese forces. ▪ The plague pandemic, also known as the Black Death, swept through Europe, the Near East, and North Africa in the 14th century and was likely 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 been suggested. History of Bioterrorism and Biological Warfare ▪ Many other incidents indicate the various uses of disease and poisons during war. ▪ For example, bodies of dead soldiers were catapulted into the ranks of the enemy in Karolstein in 1422. ▪ A similar strategy using cadavers of plague victims was utilized in 1710 during the battle between Russian troops and Swedish forces in Reval. History of Bioterrorism and Biological Warfare ▪ On numerous occasions during the past 2000 years, the use of biological agents in the form of disease, filth, and cadavers have been mentioned in historical recordings. Examples of biological and chemical warfare use during the past 2000 years Time Event 600 BC Solon uses the purgative herb hellebore during the siege of Krissa 1155 Emperor Barbarossa poisons water wells with human bodies in Tortona, Italy 1346 Tartar forces catapult bodies of plague victims over the city walls of Caffa, Crimean Peninsula (now Feodosia, Ukraine) 1495 Spanish mix wine with blood of leprosy patients to sell to their French foes in Naples, Italy 1675 German and French forces agree to not use “poisones bullets” 1710 Russian troops catapult human bodies of plague victims into Swedish cities 1763 British distribute blankets from smallpox patients to Native Americans 1797 Napoleon floods the plains around Mantua, Italy, to enhance the spread of malaria 1863 Confederates sell clothing from yellow fever and smallpox patients to Union troops during the US Civil War World War I German and French agents use glanders and anthrax World War II Japan uses plague, anthrax, and other diseases; several other countries experiment with and develop biological weapons programs 1980–1988 Iraq uses mustard gas, sarin, and tabun against Iran and ethnic groups inside Iraq during the Persian Gulf War 1995 Aum Shinrikyo uses sarin gas in the Tokyo subway system History of Bioterrorism and Biological Warfare ▪ Another disease which has been used as an effective biological weapon in the New World was smallpox. ▪ Pizarro was said to have presented South American natives with variola- contaminated clothing in the 15th century. ▪ In addition, during the French-Indian War (1754–1767), Sir Jeffrey Amherst, the commander of the British forces in North America, suggested the deliberate use of smallpox to diminish the native Indian population hostile to the British. ▪ An outbreak of smallpox in Fort Pitt led to an outbreak of fomites and provided Amherst with the means to execute his plan. On June 24, 1763, Captain Ecuyer, one of Amherst's subordinate officers, provided the Native Americans with smallpox-laden blankets from the smallpox hospital. He recorded in his journal: “I hope it will have the desired effect”. As a result, a large outbreak of smallpox occurred among the Indian tribes in the Ohio River Valley. Again, it has to be recognized that several other contacts between European colonists and Native Americans contributed to such epidemics, which had been occurring for over 200 years. In addition, the transmission of smallpox by fomites was inefficient compared with respiratory droplet transmission. History of Bioterrorism and Biological Warfare ▪ During World War I, reports circulated of attempts by Germans to ship horses and cattle inoculated with disease-producing bacteria, such as Bacillus anthracis (anthrax) and Pseudomonas pseudomallei (glanders), to the USA and other countries. ▪ The same agents were used to infect Romanian sheep which were designated for export to Russia. Other allegations of attempts by Germany to spread cholera in Italy and plague in St. Petersburg in Russia followed. ▪ Germany denied all these allegations, including the accusation that biological bombs were dropped over British positions. History of Bioterrorism and Biological Warfare ▪ In 1924, a subcommittee of the Temporary Mixed Commission of the League of Nations, in support of Germany, found no hard evidence that the bacteriological arm of warfare had been employed in war. However, the document indicated evidence of use of the chemical arm of warfare. ▪ In response to the horror of chemical warfare during World War I, international diplomatic efforts were directed toward limiting the proliferation and use of weapons of mass destruction, i.e., biological and chemical weapons. ▪ 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 eventually the 5 permanent members of the United Nations (UN) Security Council, signed the agreement. However, the Geneva Protocol did not address verification or compliance, making it a document which was less meaningful. ▪ 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 USA did not ratify the Geneva Protocol until 1975. History of Bioterrorism and Biological Warfare ▪ During World War II, some countries began a rather ambitious biological warfare research program, especially Japan. ▪ Japan conducted biological weapons research from approximately 1932 until the end of World War II. ▪ The program was under the direction of Shiro Ishii (1932–1942) and Kitano Misaji (1942–1945). ▪ There were several military units for research and development of biological warfare. The center of the Japanese biowarfare program was known as “Unit 731” and it was located in Manchuria near the town of Pingfan.  Biological warfare programs during World War II Nation Numbers of workers (estimated) Focus Germany 100–200 Offense research forbidden Canada small Animal and crop diseases, rinderpest, anthrax United Kingdom 40–50 Animal and crop diseases, anthrax, foot and mouth disease Japan several thousand Extensive; official information suppressed by a treaty with USA in which all charges for war crimes were dropped for exchange of information from experiments Soviet Union several thousand Typhus, plague USA 1500–3000 Chemical herbicides, anthrax (started too late to be important) History of Bioterrorism and Biological Warfare ▪ Besides for the experiments performed in Unit 731, the Japanese military developed plague as a biological weapon by allowing laboratory fleas to feed on plague infected rats. ▪ On several occasions, the fleas were released from aircraft over Chinese cities to initiate plague epidemics. However, the Japanese had not adequately prepared, trained, or equipped their own military personnel for the hazards of biological weapons. ▪ An attack on the city of Changteh in 1941 reportedly led to approximately 10,000 casualties due to biological weapons. During this incident 1700 deaths were reported among Japanese troops. Thus, “field trials” were terminated in 1942. History of Bioterrorism and Biological Warfare ▪ In December 1949, a Soviet military tribunal in Khabarovsk tried 12 Japanese prisoners of war for preparing and using biological weapons. ▪ The Japanese government, in turn, accused the Soviet Union of experimentation with biological weapons, referring to examples of B. anthracis, Shigella, and V. cholerae organisms recovered from Russian spies. Biological Warfare Programs After WWII ▪ During the years immediately after World War II, newspapers were filled with articles about disease outbreaks caused by foreign agents armed with biological weapons. ▪ During the Korean War, the Soviet Union, China, and North Korea accused the USA of using agents of biological warfare against North Korea. ▪ Later on, the USA admitted that it had the capability of producing such weapons, although it denied having used them. However, the credibility of the USA was undermined by its failure to ratify the Geneva Protocol of 1925, by public acknowledgment of its own offensive biological warfare program, and by suspicions of collaboration with former Unit 731 scientists. Biological Warfare After WWII ▪ By the late 1960s, the US military had developed a biological arsenal that included numerous biological pathogens, toxins, and fungal plant pathogens that could be directed against crops to induce crop failure and famine.  Fort Detrick ▪ At Fort Detrick, biological munitions were detonated inside a hollow 1-million-liter, metallic, spherical aerosolization chamber known as the “eight ball”. ▪ Volunteers inside this chamber were exposed to Francisella tularensis and Coxiella burnetii. The studies were conducted to determine the vulnerability of humans to certain aerosolized pathogens. Further testing was done to evaluate the efficacy of vaccines, prophylaxis, and therapy. During the offensive biological program (1942–1969), 456 cases of occupational infections acquired at Fort Detrick were reported at a rate of < 10 infections per 1 million hours worked. This rate of infection was well within the contemporary standards of the National Safety Council and below the rate reported from other laboratories. Three fatalities due to acquired infections were reported from Fort Detrick during this period: 2 cases of anthrax occurred in 1951 and 1958, and 1 case of viral encephalitis was reported in 1964. In addition, 48 occupational infections were reported from the other testing and production sites, but no other fatalities occurred. Bioterrorism ▪ Between 1951 and 1954, several studies were conducted to demonstrate the vulnerability of US cities. ▪ Cities on both coasts were surreptitiously used as laboratories to test aerosolization and dispersal methods when simulants were released during covert experiments in New York City, San Francisco, and other sites. Aspergillus fumigatus, Bacillus subtilis var globigii, and Serratia marcescens were selected for these experiments. Organisms were released over large areas to study the effects of solar irradiation and climatic conditions on the viability of microorganisms. ▪ Concerns regarding potential public health hazards were raised after outbreaks of urinary tract infections caused by nosocomial S. marcescens at Stanford University Hospital between September 1950 and February 1951. Bioterrorism ▪ During the late 1960s, public and expert concerns were raised internationally regarding the indiscriminate nature of, unpredictability of, the risk of and lack of control for biological weapons. ▪ In addition, more information on various nationsbiological weapons programs became evident, and it was obvious that the 1925 Geneva Protocol was ineffective in controlling biological weapons. ▪ In July 1969, Great Britain submitted a proposal to the UN Committee on Disarmament outlining the need to prohibit the development, production, and stockpiling of biological weapons. ▪ Furthermore, the proposal provided for measures for control and inspections, as well as procedures to be followed in case of violation. ▪ Shortly after submission of the British proposal, in September 1969, the Warsaw Pact nations under the lead of the Soviet Union submitted a similar proposal to the UN. However, this proposal lacked provisions for inspections. ▪ Two months later, in November 1969, the World Health Organization issued a report regarding the possible consequences of the use of biological warfare agents Bioterrorism ▪ The 1972 “Convention on the Prohibition of the Development, Production, and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on Their Destruction,” known as the BWC, was developed. ▪ This treaty prohibits the development, production, and stockpiling of pathogens or toxins in “quantities that have no justification for prophylactic, protective or other peaceful purposes”. ▪ Under the BWC, the development of delivery systems and the transfer of biological warfare technology to other countries are prohibited. ▪ It also required the parties to the BWC to destroy stockpiles, delivery systems, and production equipment within 9 months of ratifying the treaty. This agreement was reached among 103 cosigning nations, and the treaty was ratified in April 1972. ▪ The BWC went into effect in March 1975. Bioterrorism ▪ The BWC does not provide firm guidelines for inspections and control of disarmament and adherence to the protocol. ▪ In addition, there are no guidelines on enforcement and how to deal with violations. ▪ Alleged violations of the BWC were to be reported to the UN Security Council, which may in turn initiate inspections of accused parties, as well as modalities of correction. ▪ More recent events in 2003 and 2004 again illustrated the complexity and the enormous difficulties the UN faces in enforcing the statutes of the BWC. Bioterrorism ▪ In the mid 1990s, large amounts of botulinum toxin were found in a laboratory in a safe house of the Red Army Faction in Paris, France. ▪ Apparently, the toxin was never used. ▪ The bioterrorism threat resurfaced then on March 18, 1995, after the Aum Shinrikyo attacked the Tokyo subway system with sarin gas. Bacillus anthracis ▪ Bacillus anthracis is among the largest of all bacterial pathogens. Its virulence factors include a polypeptide capsule and exotoxins that in varying combinations produce edema and cell death. ▪ Anthrax has been known as a zoonotic dieasese of livestock. It has an important place in the history of medical microbiology because it was the model for Robert Koch's postulates in 1877 and then Louis Pasteur's use as proof for usefulness of a vaccine. ▪ Anthrax is a facultative anaerobe which undergoes a cycle of vegetative growth and sporulation in the soil. Animals can get infected while grazing in grass with contaminated spores. Anthrax ▪ Human infection depends on portal of entry. The most common and least dangerous of all forms is cutaneous anthrax which is caused by spores entering the skin through cuts in the skin. Germination and growth of the pathogen in the skin are marked by necrosis of the skin and formation of an eschar - a black necrotic lesion. Anthrax ▪ A more destructive form of the disease is pulmonary anthrax or inhalation anthrax caused by inhalation of airborne spores, either by contaminated soil or animal products. The infectious dose is small. ▪ Upon reaching the lungs, spores are phagocytosed and transported to the lymph nodes where they germinate and secrete exotoxins which enter the circulatory system. Toxins are highly lethal. ▪ Terrorist attacks of 2001 focused a lot on bioterrorism and inhalation anthrax was considered a weapon at that time. Botulism ▪ Botulism is caused by a toxin that attacks the body’s nerves and causes difficulty breathing, muscle paralysis, and sometimes death. ▪ This toxin is usually fro Clostridium botulinum and sometimes Clostridium butyricum and Clostridium baratii bacteria. ▪ These bacteria can produce the toxin in food, wounds, and the intestines of infants. Botulism ▪ Clostridium botulinum bacteria make spores, which act like protective coatings. ▪ Spores help the bacteria survive in the environment, even in extreme conditions. The spores usually do not cause people to get sick, even when they’re eaten. However, under certain conditions, these spores can grow and make one of the most lethal toxins known. The conditions in which the spores can grow and make toxin are: – Low-oxygen or anaerobic environment – Low acid – Low sugar – Low salt – A certain temperature range – A certain amount of water Botulism ▪ Botulinum toxin prevents the release of the neurotransmitter acetylcholine, which initiates the signal for muscle contraction. ▪ Usual time for onset of symptoms is 12-72 hours depending on the size of the dose. ▪ Neuromuscular symptoms first affect the muscles of the head and include double vision, difficulty swallowing, and dizziness, but there is no sensory or mental lapse. ▪ Nausea and vomiting can occur at an early stage but they are not common. ▪ Later symptoms include muscular paralysis and respiratory failure. Treatment of Botulism ▪ Treatment includes adminstration of botulinum antitoxin which is supplied by the CDC. ▪ This must be administered early for it to be effective. ▪ The antitoxin does not reverse the paralysis but it does stop the progression and can dramatically shorten the course of the disease. ▪ Patients are also managed with respiratory and cardiac care as needed. ▪ CDC (2021) About Botulism Atlanta, GA ▪ Mader, S. (2018). Human Biology (15th ed.). New York, NY: McGraw Hill. ▪ Riedel S. (2004). Biological warfare and bioterrorism: a historical review. Proceedings (Baylor University. Medical Center), 17(4), 400–406. https://doi.org/10.1080/08998280.2004.11928002 ▪ Talaro, K (2018) Foundations of Microbiology (10 ed.) New York NY: McGraw Hill ▪ Tortora, G. (2014) Principles of Anatomy &Physiology (14th ed.) Hoboken, NJ: John Wiley& Sons. ▪ Urry, L. (2017). Campbell Biology (11th ed.). NewYork, NY: Pearson Education. ▪ Vodopich, D. (2011). Biology Laboratory Manual (9th ed.) New York, NY: McGraw Hill.