Review Article – ARE WE READY TO FACE ANOTHER BIOLOGICAL WAR? Shahzad Ali Jiskani 1*

1Department of Pathology, Indus Medical College, Tando Muhammad Khan, Sindh *[email protected]

ABSTRACT: KEYWORDS: The bioterrorism is threatened / premeditated Bioterrorism, biological weapons, , utilization of biological agents/ weapons including zoonotics, public health INTRODUCTION: , , and various other Bioterrorism of defined as utilization of microorganisms to reason deaths and/or illness in microorganisms e.g. , bacteria and fungi etc. or plants, animals, humans etc. As majority of the certain toxic materials by extremists or terrorists' agents/products used as biological agents are groups to create weapons which result in disease and zoonotics, there is major concern about the possibility death among animals, plants and humans 1-2. to use animals as the source. Livestock owners and is defined as use of violence or force veterinarians may be the first among those who against law on nature (e.g. animals), persons or assets identify initial cases of act of bioterrorism. Biological to intimidate a civilian residents to get social or agents can be categorized into three classes. political intentions. Such agents are already present Biological agents of category (A) can cause easy naturally but there is possibility so they can be transmission from animal to human except ; transformed to enhance their power for the as it has no reservoir of animal, human to human, production of disease, increase resistance to available cause increased mortality and can cause major health therapeutic agents and/or enhance their capacity to impact globally. Agents in category (B) cause quick extension to the environment 3. The term moderate transmission; causing moderate morbidity 'bioterrorism' represents wide spectrum of and low mortality. Agents in category (C) belong to apprehensions, from disastrous terrorism by bulk characteristics which can be engineered for spreading emergencies to micro-events by minor technologies; them globally or into massive community. We lack though able to produce social discomfort, disease, the adequate capability for prevention of these disabilities, disruption, and ultimately fatality 4. The biological attacks, but prevention measures should be objective of bioterrorism does not limit to morbidity taken for decreasing the risks. For restriction of access and mortality; though it also leads towards of dangerous biological weapons to population, breakdown of public and political concerns. As this is increased laboratory testing or scrutiny for causative global concern of 21st century, the vitality to be agents, high control for investigations and proper conscious of instruments used as biological agents in measurement of prevention are necessary. Along with war is necessary. By taking these things in mind, it is human measures and testing, veterinary laboratories important to instruct healthcare professionals in front should be included in surveillance on national level – line including doctors, nurses and paramedics 5. For

AJAHS VOL-5 ISSUE-2 APR-JUN 2020 72 Bioterrorism – Are We Ready To Face Another Biological War? this, there is urgent need of surveillance between were hospitalized and 12 people died during this emergency areas, hospitals, laboratories and attack. – contaminated letters were posted to departments of public health. Staff should be well – anchor of TV news, United States senators and trained as the first responders with efficient data various others personalities in 2001. Healthcare systems and should be provided enough capacity for workers were sent to Africa on a mission, with laboratory in Emergency Department for an adequate intensionCategory to bring back theAgents/ samples Diseases of virus for response 6. In this review, knowledge regarding their use as biological weapon 7, 11. Agents utilized as Anthrax (B. anthracis) bioterrorism and its recognition has been enlightened. biological weapons are give in Table 1. Botulism (C. botulinum) History of Bioterrorism Plague (Y. pestis) The history of bioterrorism is very old. Since 600 BC, A armies and people have been exposed to certain Smallpox (V. major) infectious diseases 7. Death from plague was seen as (F. tularensis) response to it spread during member of league of Viral hemorrhagic fevers Kaffa, Feodosiya, Ukraine by attack of Tartars (Brucella spp.) th (Mongols) during 14 Century. Water was polluted by Epsilon of C. perfringens their army by throwing dead animals in water Threats to food safety e.g. Salmonella spp., E. coli O157:H7, Shigella supplies. Gabriele de'Mussi, an Italian, reported this (B. mallei) as being an eye witness 8. Pandemic of the plague, which is also called ''Black Death'', quickly spread in Melioidosis (B. pseudomallei) Psittacosis (C. psittaci) North Africa and Europe started as there was B migration of refugees from respective city. Germany Q fever (C. burnetii) and United States during World War I, tried to produce toxins from Ricinus communis (castor beans) biological weapons for contamination of animal feed. Staphylococcal enterotoxin B Native Indians were exposed by British troops with fever (R. prowazekii) linens and blankets contaminate by victims of Viral encephalitis (Alphaviruses) smallpox to spread among them in Ohio River Valley. Water safety threats (e.g. Vibrio cholerae, Cryptospodidium parvum) United States in Cold War produced biological 5, 7, 9 Nipah virus weapon arsenals . Dr. Anton Dilger worked with C anthrax cultures glanders to produce biological harm Hantovirus between 1915 and 1916 on behalf of Govt. of Detection: Germany 10. Rajneeshee, a pseudo – Buddhist cult Detection and decontamination of facilities critically spread Salmonella during 1984, in grocery-stores and affected were felt necessary after attack with Anthrax restaurants of Oregon for poisoning of civil leaders. contaminated letters in 2001 in the US. Various Russia in 1992, got the ability to launch missiles with complicated and methods for decontamination have small pox having weapon – grade. In certain, terrorist been created during recent decade 12. A great chaos can organizations tried to spread the utilization of be faced by healthcare system in case of an attack biological weapons. The subway of Tokyo was which spread in short period of time 13. Centres of exposed to Sarin gas by Aum Shinrikyo. 5000 people Disease Control (CDC) of United States is doing

AJAHS VOL-5 ISSUE-2 APR-JUN 2020 73 Bioterrorism – Are We Ready To Face Another Biological War? efforts for healthcare workers to be familiar with problems 18-20. biological war weapons by implementation of 1. Anthrax: ''Bioterrorism Preparedness and Response Program'' The anthrax disease is caused by zoonotic organism, for the detection and adequate response to any attack named Bacillus anthracis which is gram – positive by biological weapons 14. Early identification is and non – motile 21. For centuries, anthrax has necessary in decreasing emergency casualties, been the cause of curse of cattle and various other starting adequate therapy and preservation of herbivores. In the time of early revolution, it was first appropriate resources. Nevertheless, signs and documented as an occupational lung disease in labour symptoms seen in response to biological weapons are of European wool industries due to its inhalation 22-25. not specific and can easily be mistaken for common The inhalation is highly dangerous, can be produced emergencies every day. Accurate and rapid easily and be disseminated easily. These bacteria are technologies have to be made for the conformation of easy to grow on cultures the production of the spores these biological agents in various ways. These is gladly induced. Additionally, the spores of anthrax technologies should be able to identify matrices. are sunlight – resistant, heat resistant and resistant to Additionally, they should have easy access, disinfectants. These spores have ability to disperse in portability and efficient enough for the detection of wide population through bombs, missiles, flying various dangerous agents. Development of such aircrafts, and these spores can preserve their virulence technologies is still a challenge. An antigen and factors for many years; hence makes it as suitable antibody – based systems are non – specific and non – weapon for biological war 26, 27. reliable, current research is based on development of Bioterrorism uses its inhalation form and the spores sensors based on nucleic acids. These are much more have to be aerosolized. It is slightly hard because for sensitive but their preparation is very complex 15-17. that the spores have to be intermixed with fine Biological Weapons: particles by technical methods. Once the appropriate As per Centre of Disease Control (CDC), biological form is available, its spread is easy through the weapons are categorized into three categories (Table utilization of aerosol products used commercially. 1). Agents related to category A can disseminate Latest outbreak was seen in postal services by certain without problems or they can be transmitted from letters having anthrax powder. The spores of the human to human. The rate of mortality of these agents Anthrax were used as weapon by United States during is very high and they create major panic and social 1950's and 1960's prior to the termination of old disturbances globally. Category B contains agents offensive program of United States offensive which are moderate in nature for spreading. Mortality program. It was admitted by Iraq to inspection by and mortality rate of these agents is moderate and less United Nations in August 1991 that they were severe as compared to category A agents. In category involved in performing research of deadly application C, the agents used can be engineered for global of B. anthracis before Persian Gulf War. They also transmission and spreading in future because of their accepted the utilization of the organism as biological accessibility. These agents are easy to manufacture weapon in 1995. It was also declared by recent rebel and easy transmissible. Mortality and morbidity rates from former biological weapon program of Soviet of such agents are high and can affect major health Union that anthrax is used in bulk quantities by

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Soviets for biological war. This organisms can be considered as difficult to use as a biological weapon as synthesized both as dried or wet form. In 2001, recent growth and cultivation of this agents is not easy; attack by anthrax was global concern was through although it can be obtained from infected organisms. letters 25. USA experienced various biological attacks It was used as biological weapon by United States and in mid-September 2001 which involved the Soviet Union previously through aerosol intentionally spread of B. anthracis via the postal transmission. People affected with this agent present system. These letters were mailed to many important with non – specific febrile illness after 3-5 days from people in US, which affected hundreds of people. In exposure. Initial presentation can be misdiagnosed as 20th century, the mortality rate from occupationally influenza or other respiratory pathogen inhaled anthrax was 89%, which is now very reduced infection. They can also be misdiagnosed as after development of specialized care units and use of biological attack from other biological weapons 31-36. advanced antibiotics 28. 4. Plague: 2. Q Fever: This disease is produced by Y. pestis, which is rod- Q fever is illness produced by zoonotic organism shaped, gram–negative, , nonmotile and non–spore Rickettsia (C. burnetii). They reside naturally in producing organism. This agent transmits from cattle, sheep, goat, cat, dog and birds. This organism rodents (e.g. mice, rats etc.) to humans. The disease has high capability to grow into placental tissues 21. can also be transmitted to humans through fleas that While consideration to use them as biological live on rodents, leading to bubonic form of plague, weapons, they might be used; classified into lethal followed by septicaemia and pneumonia. Pneumonic (deadly) and incapacitating (weakening) agents. plague is used as potential biological weapon as it can Lethal agents (e.g. Y. pestis) cause acute illness with be easily transmitted through aerosol37, 38. Besides increased mortality rate. Although, in diseases caused smallpox, this is the only biological weapon, which by incapacitating agents, people are ill at levels where can create destruction further than those individuals they are not able to continue their normal routine life who are infected at first. Due to use of modern for a certain time, and largely people get recovery. Q antibiotics, the disease is now under control but it has fever is classified as one of the incapacitating agents, been used as a potential biological weapons due to its so it is considered that attack by this biological agent easy transmission via aerosol 39. will involve large population is transmitted as an In early history, plague was termed as ''Black Death'', aerosol. This organism is highly resistant to certain which was its bubonic – flea – borne type. But now factors and a man needs very low dose for evolution makes it other pneumonic variety to be the infectivity.29, 30 cause of epidemics. The plague was used as biological 3. Tularemia: weapon by former Soviet Union and US biological This infection is produced by F. tularensis, which is weapon programs 40-43. tiny, aerobic, nonmotile and gram – negative 5. Botulism: coccobacillus. It is zoonotic disease that is transmitted This disease is caused by Clostridium botulinum, to humans after mucous membrane or contact of skin which is obligate anaerobe and spore – forming with body fluids or infected animal tissues, or can be organism. This agent can be extracted from its natural transmitted by bite of infected ticks 21. It was territory, the soil. 4 species of C. botulinum has been

AJAHS VOL-5 ISSUE-2 APR-JUN 2020 75 Bioterrorism – Are We Ready To Face Another Biological War? identified which are characterized by different into body of individuals; Transmissibility: The genomes but common toxin of botulinum. Moreover capability of causative agent for its transmission from 7 different antigenic types (A-G) of infected to healthy individual; Neutralizing capacity: are described by lack of cross – neutralization 44, 45. The ability to act with various tools of prevention Toxin is di – chain polypeptide which contains zinc and/or therapeutic purpose 21,54. and is endopeptidase that obstructs vesicles having Biological Weapons, Their Delivery Mode and acetylcholine, from joining with terminal membrane Dissemination: of motor neuron, which cause paralysis of flaccid Biological weapons may be spread in either dry or wet muscle. Death occurs in botulism by pharyngeal and figure. Dry powders contain small particles and diaphragmatic muscle paralysis, ultimately leading to contain improved characteristic of distribution. respiratory arrest. It is major biological weapon threat Additionally it has advantage in storage. But its due to its high lethality and potency, easy production preparation is very complex by use of various and transport, misuse and need for increase time technologies; although technology of spray dries and period at intensive care 41, 42, 46, 47. freeze dying is available. Aerosolized agents are most Biological Weapons and Their Properties: commonly used. The causative mediator can be Potent biological agent used as weapon can be more distributed by attachment of spray device to a mobile efficient than hydrogen bomb. The attacks by certain transport. An example is the industrial sprayer biological agents are designed for destruction of a consists of insecticide which is designed to be population or community, either by induction of mounted on aircraft. While operating the sprayer, a disease or by assassination big amount of people. line of release occurs. It is called as line source and its Following are the characteristics of potent and ideal spray is upright to direction of the wind, upwind of biological weapon: Highly toxic, extremely target area intended. Anyone downwind up to a infectious, easily spread amongst individuals, definite sort of such line would be at danger constant, both in dispersal and storage, produce theoretically 18, 55. difficulty in measures by medical techniques, easy The range of spread of causative agent relies on growth and able to generate effects with manipulation various factors, such as speed and direction of the 48, 49. Characteristics of biological weapons are wind, stability of the atmosphere, inversion described by Eitzan 50-52. They should be easy to find conditions; and at last on the agent characteristics. and produce. High amount of biological agents is Biological weapons can be transmitted by their required to make biological attacks to target or spreading through atmosphere, by infecting the population. Appropriate selection should be made animals that transmit the illness to host human and by according to need by basis of its incubation period. foodstuff or contamination of water. There are various Routine of transmission is also required as it should reasons why biological agents used as weapons are spread easily 53. more powerfully potent agents to massive fatalities Certain factors define the health hazards; Infectivity: leading to disturbances to civil society. The model It is the ability of the causative agent to penetrate and biological weapon may be effortlessly dispersed in able to multiple within host; Pathogenicity: The open air with the use of off – the shelf devices 56, 57. capability of the causative agent for its penetration Delivery of the most effective biological weapons is

AJAHS VOL-5 ISSUE-2 APR-JUN 2020 76 Bioterrorism – Are We Ready To Face Another Biological War? through aerosol. Main objective for using this system phagocytes that, if they are not successful in is to create invisible clouds with droplets or particles destruction of pathogenic organism, they may carry it having diameters between 0.5 – 10 micrometers, to lymphatic system where its proliferation occurs which have ability to remain suspended for long time. and cause damage. In contrast to vapours, the Inhalation of such particles makes settlement deep particles of aerosol of certain sizes accumulate over into the lungs. The biological weapons may be time in lungs 66-71. utilized for contamination of foodstuff and water. For 2. Skin and Mucous Membrane: effective use of biological weapons by food is to be This route is least harmful, but injuries, skin rashes or serve by using raw material as heating will cause sores might change the scenario and allow pathogenic destruction of many microorganisms and toxins. organisms to enter. More vascular, thinner surface and Standardized purification of water may highly skin moisture increases chance of penetration by the inactivate many pathogenic organisms and some agent. Increase in humidity promotes penetration into toxins as well. Although; many spore, cysts, viruses skin. Aerosols and liquid spills can cause hazardous and many bacteria are not inactivated by chlorination effects to skin 72, 73. and commercial filtration methods. If charcoal is not 3. Digestive System: used along with filtration, toxins will not inactivate 58- Infection by this route due to food or water 61. contamination can be managed easily by the route of Biological Weapons and Their Routine of use of antibiotics. Biological agents can penetrate the Exposures: digestive tract through polluted water and/or food, Biological weapons can be transferred via one or through hand to mouth interaction after touch of the further routes, including; parenteral: causative agents surfaces that are contaminated, or via swallowing of are transmitted via blood or body fluids; droplets accumulated mucus in respiratory tract resided in (airway): causative agents are transmitted by throat/nose and upper airways. This route is most easy inhalation of contaminated droplet in environment of to control, especially, if the source of contamination is infected people; contact: causative agents can be known 72. transmitted via surface of infected organism; oral- Animals as Sentinel of Agents Used in faecal route: causative agents are transmitted through Bioterrorism: foods, objects or other substances polluted with 80% of the agents used in bioterrorism belong to faeces of infected individual, or via sexual interaction zoonotic category and they are utilized as biological 62-65. weapons 39, 74. In context of such attacks on population 1. Respiratory System: of humans, there is massive health risk to animal The inhalation of the causative agent is most population as well. So it is very recommended and dangerous route, which initially resembles flu – like important that early diagnosis of certain health symptoms but gradually leads to respiratory failure. problems in animals and establishment of criteria for Body is more prone to develop infection by this route evaluation and diagnosis of doubtful clusters of due to large surface area and function of gaseous animal and human injury or disease and ultimately exchange in lungs, due to susceptibility of mucous triggering for notification of rule enforcement of membrane to infection, and due to occurrence of suspected action of chemical or biological terrorism.

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Another indicator of attack by terrorism by biological Education regarding threats and associated risks of agents would be enhanced amount of dead or sick biological agents should be given to general animals; although various classes may be affected. population. Consumption of cooked food only and The effective utilization of animals as bioterrorism use of chlorinated/ boiled/ filtered water have to be sentinels to humans can be differentiated from encouraged. Control measures against rodents and possible activity of direct attack on animals which are insects should be initiated on immediate basis. useful in agriculture (agroterrorism). First of all, Isolation of confirmed and suspected cases is animals' give humans early warning, if one can detect mandatory. An early identification of biological war clinical symptoms and signs in animals before can control massive casualties with proper measures; development in humans, or as soon as that preventive requiring arrangement of specialized laboratories. measured can be taken. Early on exposure might Clinical knowledge and skills for physicians and happen because animal species had high vulnerability healthcare workers should be polished. By proper to agent as agent causing the illness has short period of precautions, one can prevent the effect of agents incubation or because animal exposure was sooner causing biological war. In the area of biological attack than human population18,75, 76. Manifestation of clinical or threat, specific measures should be taken including features in animals at same time might lead to fast proper protective clothing pre – exposure recognition of biological agent which produces non – prophylaxis, post – exposure prophylaxis, specific problems in persons close by. Secondly, if immunization and therapeutics. Prior to entering the causative biological agent remains in atmosphere, affected area, medical personnel must be immunized; active surveillance for sporadic animal illness can be if available. If attack is known to have occurred or felt used for detection of ongoing risk exposures. In the to be imminent, all personnel should be given end, populations of animals for example livestock, command – directed chemoprophylaxis in the area. In wild birds and other animals trading, could take part in absence of such threat, it is impractical and not spread and maintenance of epidemic which is suitable to put everyone on chemoprophylaxis. attributable to release of biological agent by Sufficient time should be given to provide early intentionally. This will provide opportunity for protection for effectiveness before personnel are prevention using certain interventions 24. positioned in the area. If there is not adequate time to Effect of Bioterrorism on Humans and Animals: wait for effectiveness of immunization, it should be Biological attack by even small – scale agent can given as soon as the mission allows. Pre – exposure cause massive mortality and morbidity. For instance, prophylaxis and post – exposure prophylaxis of these it is estimated that release of as little as 100 kg d r u g s a r e s o m e t i m e s a d d e d a l o n g w i t h aerosolized spores of anthrax upwind of Washington immunizations. If immunization of certain biological DC – sized metro city can cause deaths up to 3 million. agents is not present, the application of personal Health status of aggressor forces are also at risk while p r o t e c t i v e e q u i p m e n t i n a d d i t i o n t o preparation, transportation and delivery of biological chemoprophylaxis can be given for protection 18, 22, 77-79. agents 57. Vaccination against biological agents is very Measures and Prevention and Protection against important and practical if used prior to threat of Biological Weapons: biological war, but unfortunately vaccination against

AJAHS VOL-5 ISSUE-2 APR-JUN 2020 78 Bioterrorism – Are We Ready To Face Another Biological War? very few biological war agents are available 22. 4. Pal M, Tsegaye M, Girzaw F, Bedada H, CONCLUSIONS: Godishala V, Kandi V. An overview on Efficacy of biological agents as weapons has not been biological weapons and bioterrorism. American completely confirmed, and is not used frequently Journal of Biomedical Research. 2017;5(2):24- previously. Because human health is highly exposed 34. to naturally such as Influenza virus, where 5. Kasdorf B. EPUB 3: Not your Father's EPUB. large population is involved and very easy to transmit, Information Standards Quarterly. 2011;23(2):4. a danger of its utilization as biological weapon cannot 6. Knobler SL, Mahmoud AA, Pray LA. The be undervalued. In last century, there is continuous Research Agenda: Implications for Therapeutic attraction with biological weapons by countries, is a Countermeasures to Biological Threats. type of addiction we see even today; particularly in InBiological Threats and Terrorism: Assessing areas where regional domination may need The Science and Response Capabilities: exceptional weapons. Biological wars remain a global Workshop Summary 2002. National Academies threat. Veterinary and human medicines can get Press (US). benefit from cross – collaboration as biological 7. Stefan R. and bioterrorism: a weapons used by bioterrorists are made up majority of historical review Proc. Bayl Univ Med Cent. zoonoses. Surveillance and integration of human and 2004;17(4):400-6. veterinary public health is important in dealing 8. Christopher LG, Cieslak LT, Pavlin JA, Eitzen bioterrorism. This step needs improved collaboration EM. Biological warfare: a historical and communication. To control bioterrorism, strong perspective. Jama. 1997 Aug 6;278(5):412-7. cohesive and coordinated efforts by scientists, 9. Barras V, Greub G. History of biological v e t e r i n a r i a n s , h e a l t h c a r e p r o v i d e r s a n d w a r f a r e a n d b i o t e r r o r i s m . C l i n i c a l epidemiologists is very necessary. Microbiology and Infection. 2014 Jun REFERENCES: 1;20(6):497-502. 1. Green MS, LeDuc J, Cohen D, Franz DR. 10. Force AB, CDC Hospital Infections Program Confronting the threat of bioterrorism: realities, Bioterrorism Working Group. Bioterrorism challenges, and defensive strategies. The Lancet readiness plan: a template for healthcare Infectious Diseases. 2019 Jan 1;19(1):e2-13. facilities. ED Management (November 1999). 2. Radovanović Nenadić U, Teodorović S. Public 1999 Nov:1-5. understanding, perceptions, and information 11. Olson KB. Aum Shinrikyo: once and future sources about bioterrorism: pilot study from the threat?. Emerging infectious diseases. 1999 Republic of Serbia. Health security. 2020 Feb Jul;5(4):513. 1;18(1):29-35. 12. Vatansever F, Ferraresi C, de Sousa MV, Yin R, 3. Erenler AK, Güzel M, Baydin A. How prepared Rineh A, Sharma SK, Hamblin MR. Can are we for possible bioterrorist attacks: An biowarfare agents be defeated with light?. approach from emergency medicine Virulence. 2013 Nov 15;4(8):796-825. perspective. The Scientific World Journal. 2018 13. Keim M, Kaufmann AF. Principles for Jan 1;2018. emergency response to bioterrorism. Annals of

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