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Food and Nutrition at Risk in America: Food Insecurity, Biotechnology, Food Safety, and Bioterrorism

Julia L. Lapp, PhD, RD, CDN Julia L. Lapp Affiliations Department of Health Promotion and Physical Education, Ithaca College, Hill Center 29, Ithaca, NY 14850 Search for articles by this author

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Centers for Disease Control and Prevention. Foodborne Illness Web site. http://www.cdc.gov/ncidod/dbmd/diseaseinfo/foodborneinfections_g.htm . Updated October 25, 2005. Accessed June 3, 2010.

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DOI: https://doi.org/10.1016/j.jneb.2010.06.003

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Protecting the Nation’s Food Supply from Bioterrorism

In the aftermath of the terrorist attacks on our country in 2001, and the resulting increased focus on national security, food security has become a top priority for the food industry. Food companies have placed a strong emphasis on reviewing security programs and procedures, in order to continually improve and enhance the strength and effectiveness of our nation’s food security systems. The food industry has a long history of dealing with threats to food safety, from foodborne disease outbreaks and inadvertent contaminations to isolated incidents of product tampering and extortion. But, now, we are dealing with what heretofore was unthinkable: the intentional, widespread contamination of the food supply. The potential for the food supply being a target or tool of terrorism can no longer be viewed in hypothetical terms. Hoping and complacency are not an option. In decades past, the food industry has faced various security challenges. For example, maintaining a drug-free workplace was an emerging security challenge in the 1980s. In the 1990s, there was a growing emphasis on preventing workplace violence. The 1990s also was the decade when the threat of biological and chemical weapons came into focus. Then—with the events of 2001—terrorism and bioterrorism became a key security issue. The issue of terrorism against the food supply is one that the food industry takes very seriously. Assessing the Risk of Foodborne Terrorism In assessing the risk of intentional contamination of the food supply in the United States, the food industry has focused on three areas—what we like to refer to as the “3 P’s of Protection”: • Personnel: Companies have increased both employee screening and supervision. • Product: Companies have established more controls on ingredients and products during receiving, production, and distribution, to ensure the highest level of food safety. • Property: Companies have ensured that they have the strongest barriers in place to guard against possible intruders. The criteria for accurate risk assessment is to look at company assets, then determine both the type of potential threat that exists and the company’s vulnerabilities. It is where a company’s assets and vulnerabilities overlap with potential threats that the risk of bioterrorism lies. Can risk be eliminated? No, because 100% security doesn’t exist. So, we must manage risk. In managing risk, deterrence and prevention are the key. The philosophy must be: “Prevent to Protect.” In a perfect world, food companies would be able to deter or prevent bioterrorism before it occurs. However, this is not a perfect world, so food companies also must have the knowledge and tools to detect and mitigate any possible food security breaches. Certainly, the goal is to detect problems, before we have to mitigate their potential impact. Protecting the Nation’s Food Security: The Food Industry’s Activities Since the day following the terrorist attacks of 2001, the food industry has been extraordinarily active in reviewing existing food security programs and implementing, as appropriate, new preventive practices and effective controls. Food companies across the country have redoubled their commitment and increased their vigilance to ensure that systems are in place to minimize and, to the extent possible, eliminate the threat of intentional contamination of the food supply. In order to be successful in enhancing their security efforts, food companies must establish a “security philosophy,” by understanding how security works, determining what their needs are, and then establishing priorities. They must review their current security practices and procedures; review their crisis management and security plans; and determine what changes or additions are needed. It is important to note that “food security” and “food safety” are not the same thing. The basic distinction is that food safety deals with accidents, such as cross-contamination and process failure during production. Food security, on the other hand, is a broader issue dealing with intentional threats. It is the intentional versus the accidental; the diabolical intent versus the chance occurrence; the deliberate versus the unplanned. These are immensely important distinctions to the food processing industry, particularly as they relate to our management and prevention practices. However, both food safety and food security activities have a common goal, which is to prevent problems that could undermine the safety of the end product to consumers. It is vital that one underlying principle be kept in sight: Although security is critical to our business, ensuring security cannot be allowed to result in business paralysis. So, any changes to either industry security activities—or to the regulations governing food security—must be both realistic and workable. When all is said and done: Reason must rule!

Read the sidebar "Where to Secure Information" Rhona S. Applebaum, Ph.D., is Executive Vice President and Chief Science Officer for the National Food Processors Association (NFPA). NFPA is the largest U.S. food trade association, representing the $500 billion food processing industry on scientific and public policy issues involving food safety, food security, nutrition, technical and regulatory matters and consumer affairs. NFPA’s three scientific centers, its scientists, government affairs experts and professional staff represent food industry interests on government and regulatory affairs and provide research, technical services, education, communications and crisis management support for the association’s U.S. and international members. Visit www.nfpa-food.org for information on food safety and security issues.

Where to Secure Information

All food processors and handlers should visit the FDA website for more complete information and to download Bioterrorism Act related publications, compliance guidance documents and notices of interim final rules and public comment periods (www.cfsan.fda.gov). Essentially, FDA is actively working on the regulatory implementation of the following four provisions in Title III, Subtitle A of the Bioterrorism Act: • Section 303: Administrative Detention. “Authorizes the Secretary of Health and Human Services, through FDA, to order the detention of food if an officer or qualified employee has credible evidence or information indicating an article of food presents a threat of serious adverse health consequences or death to humans or animals. The Act requires the Secretary, through FDA, to issue final regulations to expedite enforcement actions on perishable foods.” A regulation regarding this provision, which will provide for the means and methods for the detaining of foods suspected of terrorist tampering, has been proposed by FDA and is expected to be implemented by June 2004. • Section 305: Registration of Food and Animal Feed Facilities. “Requires the owner, operator, or agent in charge of a domestic or foreign facility to register with FDA no later than Dec. 12, 2003. Facilities are defined as any factory, warehouse, or establishment, including importers, that manufacture, process, pack or hold food for human or animal consumption in the United States.” In October 2003, the agency published an interim final rule mandating every food facility, large and small, domestic and foreign, to register with the FDA by Dec. 12, 2003. Registration consists of providing information, such as the firm name, address, product brands and categories. Farms, restaurants, retail food establishments, nonprofit establishments that prepare or serve food, and fishing vessels not engaged in processing are exempt from this requirement. Also exempt are foreign facilities, if the food from the facility is to undergo further processing or packaging by another facility before it is exported to the U.S., or if the facility performs a minimal activity such as putting on a label. Other than these exemptions, states FDA, “the registration requirements apply to all facilities that manufacture, process, pack or hold food regulated by FDA, including animal feed, dietary supplements, infant formula, beverages (including alcoholic beverages) and food additives.” FDA, which anticipates approximately 420,000 food facilities to register under this mandate, expects that such a roster will enable the agency to quickly identify and locate affected food processors and other establishments in the event of deliberate or accidental contamination of food. • Section 306: Establishment and Maintenance of Records. “Requires the Secretary of Health and Human Services to establish requirements by Dec. 12, 2003 for the creation and maintenance of records needed to determine the immediate previous sources and the immediate subsequent recipients of food, (i.e., one up, one down). Such records are to allow FDA to address credible threats of serious adverse health consequences or death to humans or animals. Entities subject to these provisions are those that manufacture, process, pack, transport, distribute, receive, hold or import food. Farms and restaurants are exempt from these requirements.” A regulation regarding the provision pertaining to record keeping has been proposed by FDA and is expected to be implemented by June 2004. The record keeping requirements will be phased in over an 18-month period from the promulgation of the regulation. This regulation will require the traceability of all foods, “one up, one down,” much as we have been doing in the organic industry for decades. However, the regulations require significantly more information and facilities will be required to respond with the records within four hours of requests made Monday through Friday, and within eight hours at all other times. • Section 307: Prior Notice of Imported Food Shipments. “Requires that prior notice of imported food shipments be given to FDA. The notice must include a description of the article, the manufacturer and shipper, the grower (if known), the country of origin, the country from which the article is shipped, and the anticipated port of entry. The Secretary of Health and Human Services, through FDA, must issue final regulations by Dec. 12, 2003.” This regulation, which mandates that importers of food must give the FDA prior notice of every shipment of food before it can enter into the U.S, was published as an interim final rule in the Oct. 10, 2003 issue of the Federal Register. Issued jointly with the U.S. Bureau of Customs and Border Protection (CBP), the advance notification of what shipments contain and when they will arrive at our nation’s ports of entry is designed to help these federal agencies better target and conduct inspections of imported foods. The agency has estimated that it expects to receive approximately 25,000 such notifications per day. Currently, FDA requires that companies must provide prior notice and receive FDA confirmation no more than five days before its arrival at a U.S. port of entry and no fewer than two hours before arrival by land via road; four hours before arrival by air or by land via rail; or eight hours before arrival by water. The agency indicates that this rule will have a phase-in compliance period through Aug. 12, 2004.

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“Food Deserts” and the Geography of Hunger

Editor’s Note: This is part of a series of postings by students in a graduate seminar on food justice at the University of New Orleans. You can read more about the class and find the syllabus here . The class is part of a new PhD program in Justice Studies at UNO.

Bob Danton University of New Orleans

When I was young and still looking at the world through rose-colored glasses, I had the opportunity to travel to Russia for three weeks, as part of an international humanitarian clowning trip led by Patch Adams and the Gesundheit! Institute . As my first trip outside the United States, I experienced “culture shock” on a wide array of different levels. This was my first time navigating what was, to me, a truly foreign food system.

One day, after an exhausting but deeply rewarding bout of clowning, we were offered a respite in the form of tea. Nestled somewhere deep inside in a large brutalist Soviet-era building, we were presented with a delightful array of meat pastries and biscuits and many things I didn’t recognize then and have since forgotten. After regaining some energy, I found myself filled with questions for our host, and asked one which at the time seemed simple, and in retrospect seems painfully naïve: ‘was your life better under the communist USSR, or is it better now under capitalism?’

The woman pondered for just a moment before responding simply ‘I used to stand in a line for bread; now I have no money for bread.’ While many years have passed and I cannot promise to quote her words exactly, the message was clear: nothing had truly changed materially in her life. Here, in one of the biggest cities in the world, capital of a global superpower, surrounded by glittering skyscrapers, palaces, and other symbols of extravagant wealth, was a woman who was deeply food insecure; and despite my naivety, I was acutely aware that her situation was likely not far from the norm. Suddenly I lost my appetite for the delicious meat pies in front of me: in front of us visitors was more food than she probably fed her family in a week. The rose-colored glasses had shattered.

Whether in Moscow or in New Orleans, Louisiana where I live and where I am studying Food Justice with Dr. Beriss, urban citizens across the globe, in nations both rich and poor, live with food insecurity every day. This insecurity, while pervasive and global, is also spatially located. Most of us by now have heard and become familiar with the concept of ‘food deserts’ as geographical areas where food is inaccessible. In her book Black Food Geographies, Dr. Ashanté Reese tackles this terminology in the context of her study of food geographies in the Black neighborhood of Deanwood in Washington, DC. She effectively argues against the use of the term, noting that its origin in the field of natural (physical) geography implies a given state; that is, it implies that the ‘food desert,’ like a real desert, is a naturally occurring phenomena, and not the result of human factors as is the case in reality. ‘Food swamps,’ a newer term created to designate areas with an overabundance of unhealthy and low-nutritional value foods, can be critiqued in this same light; these are human-made geographies, not naturally occurring phenomena like deserts and swamps. Reese explores other terms including ‘supermarket redlining,’ which she argues is too narrow in its focus on supermarkets (a critique she also places on much of the current literature on urban ‘food deserts’) and instead offers the phrase ‘food apartheid.’ Reese frames the new phrase as able to demonstrate the social and economic factors leading to the creation of these points of inaccessibility; like formal apartheid, she argues that there is a broad structural and ideological policy of racism which keeps Black people separate, subordinate, and in this particular instance, deprived of access to (healthy) food. Dr. Nathan McClintock further explores these power balances in the food systems (or lack thereof) in Oakland, California, linking lack of food access in the flatlands of East and West Oakland directly to the city’s history of legal redlining and institutionalized spatial racism.

How then, should we perceive the spatial elements of hunger, especially as they play out in urban cores, in an increasingly globalized world? Perhaps it is time to develop a new terminology, one that considers the pervasiveness of unequal development in cities around the world. I have, for much of my time in New Orleans, and in the San Francisco Bay Area before that, lived in spaces that may be termed ‘food deserts.’ As a middle-class white man, I hardly feel that it would be just to describe myself as a victim of ‘food apartheid,’ despite factors such as my lack of a car often meaning I must travel farther than I would like to on bike or foot to buy groceries. For my Russian hostess, on the other hand, that term seems perhaps more appropriate; despite the lack of a racial element in her situation, it is clear that there has been systematic repression of access and power in her life- even, in fact, transcending national regime and economic shifts.

Food, considered by many to be one of the most basic human rights, can be an effective window into broader considerations of justice in our society. Jason Hackworth, professor of geography and planning at the University of Toronto, examines in depth the issue of unequal urban development in his book The Neoliberal City . His basic thesis revolves around the modern trend towards increasingly blurred lines between political and economic actors in American cities and the massively unequal development that has resulted from what he terms ‘glocalization,’ a simultaneous movement of power from the national and state levels downward to local governments and upwards to transnational corporations. The power balance between these actors is clear: the corporations outpower the local governments. The resulting uneven development affects not only the homes and other real estate Hackworth examines, but our food as well. The end result is a system wherein local governments and the communities and people they represent are left with few options to respond to problems such as major grocery chains disinvesting in poor inner-city neighborhoods. Even if an enlightened Oakland wanted to repair the inequalities created by its historic racist politics, it no longer has any real power to do so- the city’s power is dwarfed by that of the transnational corporate forces now in control of our foodways. The power over our food access has been transferred wholesale from our communities and governments into the cold and uncaring hands of the “free market.”

Taking into account these factors I argue that we need a new terminology for our spatial awareness of disparities in our globalized food system. I am no more a victim of ‘food apartheid’ than the residents of Deanwood are inhabitants of some naturally occurring, unchanging ‘desert.’ The woman I met in Russia was not a victim of ‘supermarket redlining’ but rather of a much broader set of economic policies in Russia that have largely kept the poor poor from feudalism through communism and into capitalism. What we all share is a level of food insecurity that has a spatial dimension in our local cities as well as a relationship to massive transnational corporations and economic processes. Viewing food access through a spatial lens allows us to understand broader patterns of injustice in the world, explore ways in which local community identities and cultures are linked to and influenced by global economic factors, and see more clearly the ties between community, culture, economy, and power. Residents of Deanwood see food access as linked to factors in their community far beyond access itself; a grocery store in the neighborhood to them also represents both economic power and community identity, both now under massive pressure from powerful neoliberal forces. Driving or bussing to neighboring states or richer neighborhoods in D.C. for access to good food, beyond merely being a hardship, takes money out of Deanwood, removes the local food store as a location of community and cultural interaction, and erodes civic pride in the neighborhood.

Terminology can be important to framing the way we see the world; just as the phrase ‘the third world’ has been understood as racist and gradually replaced with ‘developing world’ or ‘global south’, we must be aware that the way we talk about areas lacking food access and the people who live within them have real world effects on our efforts to create change. Perhaps then, it is time to retire ‘food desert.’ Indeed, there may be no single term that meets our needs to describe differing, localized patterns of hunger; food apartheid may be a great fit for Deanwood, but perhaps not for Moscow, or for poor rural white communities in America. Although I do not yet have the answer as to an ideal new terminology for these globally created, transnationally connected, hyper-locally expressed patterns of food insecurity and in-access, I believe it is a conversation worth pursuing.

Hackworth, J. (2007). The Neoliberal City: Governance, Ideology, and Development in American Urbanism . Cornell University Press.

McClintock, N. (2011). From Industrial Garden to Food Desert: Demarcated Devaluation in the Flatlands of Oakland, California. In A. H. Alkon & J. Agyeman (Eds.), Cultivating Food Justice: Race, Class, and Sustainability (pp. 89–120). The MIT Press.

Reese, A. M. (2019). Black Food Geographies: Race, Self-Reliance, and Food Access in Washington, D.C. University of North Carolina Press.

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Food Shortages and Ration Reforms in the Towns and Cities: Moscow and Beyond

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Nicholas Ganson

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T he effects of natural disaster on a society depend, to a great degree, on the state of that society at the time that tragedy strikes. As David Arnold points out, “famine [often] acts as a revealing commentary upon a society’s deeper and more enduring difficulties.” 1 World War II brought ruin to the Soviet countryside and peasantry. The war’s legacy—the dearth of mechanization and shortage of work hands—coupled with peasant dependence on the state, led to a poor harvest. Similarly, the Soviet government’s established ideology shaped the way that it confronted the agricultural shortfall. Stalin and his associates reaffirmed the superiority of the exploitative collective farm system and forced society to carry the burden of the postwar hardships. These measures allowed them to pursue prerogatives deemed important by the state: the rebuilding of industry and prestige on the world political stage.

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David Arnold, Famine: Social Crisis and Historical Change (Oxford: Basil Blackwell, 1988), 7.

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M.A. Vyltsan, Krest’ianstvo Rossii v gody Bol’shoi Voiny, 1941–1945: Pirrova pobeda (Moscow: Rossiiskii nauchnyi fond, 1995), 31–32.

Andrea Graziosi and O.V. Khlevniuk, eds., Sovetskaia zhizn’, 1945–1953 (Moscow: ROSSPEN, 2003), 69.

RGASPI, f. 17, op. 88, d. 695, ll. 137–38. See also V.F. Zima, Golod v SSSR 1946–1947 godov: Proiskhozhdenie i posledstviia (Moscow: Institut rossiiskoi istorii RAN, 1996), 76.

A.V. Liubimov, Torgovlia i snabzhenie v gody Velikoi Otechestvennoi voiny (Moscow: Izdatel’stvo Ekonomika, 1968), 202. In Moscow, rumors of drought across much of the USSR were already widespread by July 1946.

See A.S. Kiselev, ed., Moskva poslevoennaia, 1945–1947: Arkhivnye dokumenty i materialy (Moscow: Mosgorarkhiv, 2000), 162.

See Donald A. Filtzer, Soviet Workers and Late Stalinism: Labour and the Restoration of the Stalinist System after World War II (Cambridge: Cambridge University Press, 2002), 49. Before the reform, for example, a kilogram of rye bread costed 1.10 rubles at ration prices but 10 rubles at commercial prices.

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This sentiment was reflected in letters written to various representatives of the central government, including Stalin himself. See E.Iu. Zubkova, Poslevoennoe sovetskoe obshchestvo: Politika i povsednevnost’, 1945–1953 (Moscow: ROSSPEN, 2000), 171–81. It is, however, difficult to what extent this faith in Stalin might have been feigned in order to achieve a desired effect.

GARF, f. 5452, op. 28, d. 1212, l. 47. Having recognized the ominous situation with the state’s grain reserves, Stalin quickly found those responsible: Minister of Trade Liubimov and Minister of Provisioning A.I. Mikoian. According to D.V. Pavlov, Stalin appointed a commission to find out who was responsible for increase in the state’s grain expenditures. The commission found Liubimov and his subordinates responsible and recommended that Liubimov be removed. The Supreme Soviet rebuked Liubimov, stopping short from relieving him of his post, but these events set the stage for his removal in 1948. See Dmitrii Vasil’evich Pavlov, Stoikost’ (Moscow: Politizdat, 1983), 194–95, < http://militera.lib.ru /memo/russian/pavlov_db/17.html> (February 26, 2006). But it appears that Stalin reserved the harshest criticism for Mikoian, who “owing to a lack in character surrounded himself with thieves.”

See Andrea Graziosi and O.V. Khlevniuk, eds., Politbiuro TsK VKP(b) i Soviet Ministrov SSSR, 1945–1953 (Moscow: ROSSPEN, 2002), 224–25.

Paul Kesaris, ed., Confidential State Department Central Files: The Soviet Union Internal Affairs, 1945–1949 (Frederick, MD: University Publications of America, Inc., 1984), microfilm, reel 1, 982–83.

See Julie Hessler, “Postwar Normalisation and Its Limits in the USSR: The Case of Trade,” Europe—Asia Studies 53, no. 3 (2001): 450.

See Amartya Sen, Poverty and Famines: An Essay on Entitlement and Deprivation (Oxford: Clarendon Press, 1981). Sen documents cases of famine with no FAD, or food availability decline, in order to suggest that a breakdown of entitlement can cause famine in overall boom conditions.

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Ganson, N. (2009). Food Shortages and Ration Reforms in the Towns and Cities: Moscow and Beyond. In: The Soviet Famine of 1946–47 in Global and Historical Perspective. Palgrave Macmillan, New York. https://doi.org/10.1057/9780230620964_3

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Fear and loathing in moscow

The Russian biological weapons program in 2022

By Robert Petersen October 5, 2022

On February 24, Russia launched a war of conquest against Ukraine after it had already illegally annexed Crimea in 2014 and waged war for eight years in the Donbas. The invasion was widely condemned, including by the United Nations General Assembly , with 141 states voting in favor of a resolution directed against the invasion, five against, and 35 states abstaining, with 12 not present.

The Russian invasion was accompanied by a disinformation campaign that claimed the United States had a secret biological weapons program in Ukraine. The roots of this disinformation campaign can be traced to 2009, but suddenly it became one of the official reasons for the Russian invasion against Ukraine. In the first weeks of the war, this created concerns that Russia might use these false allegations as a pretext to conduct an attack with its own weapons of mass destruction.

The Russian accusations and the fears they evoked raise an important question: What is the status of Russia’s own biological weapons program? The Russian government inherited a substantial part of the Soviet biological weapons program following the collapse of the Soviet Union, and what happened to this large program is a mystery. According to the US State Department , the Russian government continues to have a biological weapons program, and the US government did impose sanctions on several Russian military-biological facilities in 2021.

Although Russia is highly secretive with regard to its biological research enterprise, and there is no definitive proof of an extant bioweapons program, the public record strongly suggests that Russia has maintained and modernized the surviving parts of the Soviet biological weapons program. For instance, the Russian government repeatedly admitted and then, in subsequent years, repeatedly denied inheriting a large part of the Soviet biological weapons program. Also, there are public signs of continuing research into biological weapons (including non-lethal biological weapons) at several locations in Russia. Meanwhile, discussion and policy decisions regarding so-called genetic weapons demonstrate the Russian leadership’s obsession with the idea of a new generation of advanced bioweapons.

Any Russian attempt to conduct research on new biological weapons will face serious obstacles typical in contemporary Russia, including corruption, poor management, and a loss of expertise (accelerated by the Ukraine invasion). Nevertheless, as this article shows, the Russian government is sufficiently devoted to biological weapons to overcome these problems, if it decides to do so.

inheritance

The Soviet inheritance

A statue of Vladimir Lenin stands in the city center in Yekaterinburg. In the aftermath of the Soviet collapse, Russian president Boris Yeltsin acknowledged the existence of an illegal biological weapons program to the UN. The admission would be rescinded years later.

In December 1991, the Soviet Union collapsed, but what happened to the Soviet biological weapons program was more complicated. Soviet research into biological warfare began in the 1920s , was assembled into a biological weapons program in 1928, and continued throughout the Cold War. The Soviet Union was a signatory to the Biological and Toxin Weapons Convention (BTWC) in 1972, which banned biological weapons, but the Soviet government intentionally ignored its treaty obligations. Instead, the program was expanded through the creation of the quasi-civilian biotechnology research organization Biopreparat in the 1970s to exploit the novel possibilities in genetic engineering. The program peaked in the 1980s with an estimated 65,000 employees working at dozens of military or civilian facilities. Due to strict secrecy, the full scale of the program and what it managed to accomplish largely eluded Western intelligence. Even accidents like the deadly leak of weaponized Bacillus anthracis from the bioweapons facility Sverdlovsk-19 in April 1979 did not reveal the full scale of the program, although it did arouse suspicion among some US and British intelligence officials that the Soviet Union was not upholding the biological weapons treaty.

In 1989, Vladimir Pasechnik, a senior scientist from Biopreparat, defected and revealed key details about illegal Soviet bioweapons research to UK and US intelligence. Pressure began to mount on the Soviet government to admit to and—more important—to end these activities. In September 1991, Soviet leader Mikhail Gorbachev was confronted by the British Prime Minister John Major about the Soviet Union’s vast and illegal bioweapons program. Unlike previous encounters about the issue, Gorbachev did not deny the charge this time, but claimed that he had been misled by other senior Soviet officials. In November 1991, the Kremlin informed the UK that an order to terminate the Soviet biological weapons program had been issued.

Following the Soviet collapse, Russian president Boris Yeltsin on several occasions acknowledged the existence of an illegal biological weapons program, and some details about the program were included for the first time in a Confidence Building Measure submitted to the UN in 1992. All previous annual Soviet submissions had denied the existence of any offensive biological weapons program. During the same year, the UK, the United States, and Russia concluded the Trilateral Agreement, which reaffirmed their commitment to the Biological and Toxin Weapons Convention and declared that Russia would eliminate the biological weapons program on its territory. The agreement also provided a mechanism for the parties to conduct inspections on each other’s territory to ensure compliance.

The Russians quickly broke the promises in the Trilateral Agreement, and in May 1994, the Russian government suddenly withdrew Yeltsin’s admission that it had inherited large parts of the Soviet bioweapons program. The Russian government also claimed that US companies were violating the biological weapons treaty and demanded access to overseas US military laboratories. Russia would later claim that these US laboratories were secret bioweapons facilities. The Trilateral Agreement was finally put to rest in November 1995 , when a senior Russian diplomat declared at the Fourth Biological and Toxin Weapons Convention Review Conference in Geneva that Russia had never developed, produced, stockpiled, or stored biological weapons. This remains the Russian government position to this day.

The collapse of the Trilateral Agreement should have created an uproar, but it did not. Russian democracy was fighting for its survival by the mid-1990s, and the West set aside the question of whether Russia continued to maintain a biological weapons program in favor of what was considered to be a more important issue: supporting the Yeltsin administration. The United States and other Western countries hoped that another mechanism would alleviate at least some concerns about Russian bioweapons activities, and in 1991, the United States initiated the Cooperative Threat Reduction program. That program aimed to assist the Soviet Union and later Russia in preventing nuclear materials and weapons from falling into the wrong hands. Later, it was expanded to include the elimination of the former Soviet chemical weapons stockpile and production facilities, along with the conversion of the Biopreparat facilities to peaceful uses. The latter would serve to keep pathogens from being misused, stolen, or accidentally released from those facilities, while at the same time preventing a brain drain of scientists or technicians to countries such as Iraq or North Korea. Although it was never intended to replace the Trilateral Agreement, the Cooperative Threat Reduction program did provide some degree of reassurance that large parts of the former Soviet bioweapons program were no longer active.

Nevertheless, there were reasons for concern: The three Soviet military bioweapons facilities at Sergiev Posad-6 (previously Zagorsk-6), Yekaterinburg-19 (previously Sverdlovsk-19), and the Kirov Institute remained as they had been in the Soviet era and inaccessible to foreigners. These military facilities had been used for research and development and also weaponization and production of biological weapons. The anti-plague system (which had played a key role in the defensive part of the Soviet bioweapons program) also remained largely closed to foreigners. Because of lack of access, the Cooperative Threat Reduction program never included these facilities in its activities. According to the Russian press , scientists at Sergiev Posad-6 finished working on weaponized Monkeypox, Lassa virus, and Ebola virus in the early 1990s. Lassa virus was viewed as an especially attractive bioweapon, because the "probable adversary" (i.e. the United States) did not have the means of prevention or treatment. Ebola virus was viewed as an attractive combat virus due to its lethality, although it was a very difficult virus to cultivate.

Vladimir Pasechnik, a senior scientist from Biopreparat who defected in 1989 and revealed key details about the Soviet bioweapons research. ( FederalCity.ru )

A renewed biological weapons program?

Acting President Vladimir Putin participates in a farewell ceremony for an airborne regiment leaving Chechnya in March 2000. ( The Kremlin )

Things began to change due to the growing threat of terrorism, which became a serious issue in Russia because of the wars against Chechnya. In July 1999, there was an outbreak of Congo-Crimea hemorrhagic fever in Oblivskaya in the Rostov region of southern Russia. Although not described as a bioterrorist attack, the outbreak nevertheless served to galvanize the old biological weapons program and provide it with a new mission. Reportedly, Chechen separatists tried in 2000 to infiltrate Sergiev Posad-6 in an effort to obtain pathogens, which may also have influenced Russian decision-makers at the time. The government issued two decrees in 1999 intended to protect the Russian people against manmade or natural biological threats, including by designating Sergiev Posad-6 and the Volgograd Anti-Plague Institute as leading biopreparedness institutions. These decrees incidentally also allowed both facilities to continue highly advanced dual use-research on dangerous pathogens, including by conducting aerosol experiments. As the Swedish defense institute FOI noted in a report about the two facilities: "In this context, the unchanged focus regarding pathogens studied expertise in aerosol and research that can contribute to both defensive and offensive aims at the two new centres and their mother institutes are notable."

The administrative status of the Russian bioweapons program was further modified with government decree no. 303 in 2005, which described the Russian Nuclear, Biological and Chemical (NBC) Protection Troops as the leading organization defending against biological threats. The 48th Central Scientific Research Institute (48th CSRI) of the Russian Defence Ministry was one of several specialized organizations, which would support the Russian NBC Protection Troops. The 48th CSRI was formally established in 2006 and encompassed all the former bioweapons facilities belonging to the Soviet military. Several of the old Biopreparat facilities now became part of Rospotrebnadzor, which was responsible for human health and consumer rights in Russia. These included for example the State Research Center of Virology and Biotechnology VECTOR in Koltsovo and all of the anti-plague facilities.

Despite the official emphasis on biopreparedness, signs of biological weapons activities continued to appear. In 2004, the Russian newspaper Moskovskij Komsomolets proudly proclaimed about Sergiev Posad-6 : "According to some sources, all the production facilities of the underground part of Zagorsk-6 are kept in perfect order, including the lines for the production of ammunition based on the smallpox virus. We are ready for biological warfare." In 2005, the Military Industrial Commission and the Security Council of the Russian Federation approved a new concept for the research and development of different kinds of non-lethal weapons that could be used against living targets or to disable equipment and objects. Among these non-lethal weapons were microorganisms capable of infecting people, animals, and plants and destroying weapons and machines. One example of such research involved bacteria that could decompose lubricants over a period of days, leading to blockage of fuel lines and destruction of combustion engines. According to a 2020 report by the nonprofit research organization MITRE , Russian research and development of non-lethal weapons (including biological agents) continues.

Based on the available evidence, it is reasonable to conclude that the Russian biological weapons program was officially reconstituted as a biodefense program in the 1999-2006 time frame. During the same period, signs of biological weapons activities continued to appear in the press and other public reporting. If the Russian press is correct, the 48th CSRI retained the capability to produce biological weapons for large-scale warfare. At the same time, the Russian interest in non-lethal weapons (including those of a biological nature) is interesting and could be viewed as an attempt to adapt the program to perceived new security threats such as terrorism and insurgencies.

The first Chechen war of independence took place from 1994–1996, culminating in the Battle of Grozny and a peace treaty in 1997. In August 1999, separatist Islamic fighters from Chechnya declared themselves an independent state and set off the Second Chechen War. Russia accused the separatists of using chemical weapons while the Russian military conducted bombing raids of Grozny. ( Mikhail Evstafiev, CC BY-SA 3.0 , via Wikimedia Commons)

The 48th Central Scientific Research Institute

Colonel Sergey Borisevich, head of the 48th Central Scientific Research Institute, receiving an award from Russian President Vladimir Putin on his work developing the Sputnik-V vaccine. ( The Kremlin )

The 48th Central Scientific Research Institute employs about 1,400 people, has an annual budget of approximately 1.5 billion rubles (about $25 million), and is headed by Colonel Sergey Borisevich . According to Raymond A. Zilinskas and Philippe Mauger's book " Biosecurity in Putin's Russia , "the 48th CSRI belongs to the Russian Ministry of Defense and is supervised by the Russian General Staff. The Kirov Institute is the leading facility in the 48th CSRI and played an important role in Soviet times by developing bioweapons such as Francisella tularensis, Yersenia pestis and Bacillus anthracis . In Soviet times, the Kirov Institute had at least one BSL-3 laboratory, a vivarium—a contained observation area—for animals used in testing, several aerosol test chambers, one explosion chamber, a pilot plant, and a small production plant. The facility continues to conduct research on primates , so it is safe to say that the vivarium remains in use. In recent years, the Kirov Institute has received funding for renovation of buildings and modernization of production systems for medical immunobiological preparations against Bacillus anthracis and vaccines against Yersinia pestis , the bacterium that causes plague in humans.

Yekaterinburg-19 was partly modernized in 2005-2010 and again in 2014-2015. Several bunker facilities previously used for the storage of biological weapons remain in use. [1] Information in the public domain shows that Yekatarinburg-19 has received funding for major renovations of laboratory and production facilities and the facility’s physical protection system. Almost all of the buildings have received new roofs, and a new factory for the production of antibiotics has been built. In addition, an open-air test site called Pyshma is being modernized. In Soviet times, Pyshma was being used to test military equipment against biological weapons simulants, but presumable it would also be possible to test real biological weapons there.

Sergiev Posad-6 contains a large collection of viruses and rickettsia, conducts research on primates (including rhesus macaques), and develops vaccines against the Venezuelan equine encephalomyelitis virus and the Ebola virus. The facility also produces vaccines against Bacillus anthracis, Yersinia pestis and Variola major . There is once again evidence of major renovation projects, for example of laboratory and production facilities. Officially, Sergiev Posad-6 has the necessary capabilities to make diagnostics and treatments for dangerous viral and rickettsial pathogens. The facility also has a mobilization capacity to produce therapeutic or immunobiological medicines.

In 2016, a fourth facility belonging to the 48th CSRI was established in Moscow. The facility was in 2016 headed by Colonel Dmitry Poklonsky and had among its staff six doctors and nine PhDs. The purpose of this unnamed center is to monitor the biological situation in Russia, while being ready to respond with practical and methodological assistance in case of an emergency.

Based on 36 articles published between 2008 and 2017 [2] , the 48th CSRI’s main focus seems to be on medical countermeasures, epidemiology, diagnostics, and aerosol studies. The 48th CSRI appears to have strong capabilities in molecular biology, toxicology, and immunology. The institute has in recent years acquired a wide array of laboratory equipment that indicates the use of molecular biology and gene editing in scientific work. The 48th CSRI is, for example, using DNA/RNA synthesizers and has several times ordered ligases, restriction enzymes, and transfection reagents.

The 48th CSRI does not exist in isolation: For example, Sergiev Posad-6 has a close working relationship with the Volgograd Anti-Plague Institute. Sergiev Posad-6 specializes in viruses and rickettsia, while the Volgograd Anti-Plague Institute concentrates on bacterial and fungal pathogens. During the COVID-19 pandemic , several former Biopreparat facilities and the Gamaleya National Center of Epidemiology and Microbiology of the Russian Ministry of Health collaborated with the 48th CSRI in developing and producing the Sputnik V-vaccine. In an interview with Krasnaya Zvezda , the director of the Gamaleya Institute, Alexander Gintsburg, proudly stated that he "inherited" a strong collaboration with the military dating back to the Soviet biological weapons program.

The 48th CSRI also collaborates with the FSB, the principal Russian intelligence agency. The relationship between the 48th CSRI and the FSB dates back to an executive order from 2005. In December 2020, OpenFacto , a nonprofit association that promotes French language open-source intelligence efforts, revealed that the 48th CSRI had cooperated with FSB Unit 68240 about a project called Toledo. The operational management of Project Toledo was delegated to Unit 34435, the FSB Criminalistics Institute. The purpose of Project Toledo is unknown, but Unit 34435 is infamous for having a secretive poison laboratory, which played a key role in assassinations in Soviet times. More recently, Unit 34435 has been investigated in connection with the failed attempt to kill Russian opposition leader Alexei Navalny using a Novichok nerve agent. It therefore seems possible that the 48th CSRI assists the FSB in developing new "tools" to eliminate perceived enemies of the Russian state.

The above description presents some aspects of the 48th CSRI. It clearly has strong scientific and technical capabilities, and it has maintained old networks with former collaborators in the Soviet bioweapons program while creating new bonds with the FSB.

“More rats than cats”

Trash piles up in Sergiev Posad-6. Residents have protested against the living conditions in the town. ( AltGazeta.ru )

There is another aspect of the 48th CSRI that requires explanation. The Russia-Ukraine War has revealed deep structural problems in the Russian military due to malpractice, theft, and corruption at all levels. Perhaps this should not have come as a surprise to observers of the Russian military. The Swedish defense institute FOI recently quoted an anonymous Russian oligarch in exile as saying: "And how will the army be good, if everything else in the country is shit and mired in nepotism, sycophancy, and servility?"

There are many signs of such problems in the 48th CSRI. In February 2022 , the newsler.ru website reported that a military hospital located at the Kirov Institute was in such a poor state that bricks were falling from the walls and ceiling, endangering the lives of patients and staff. Sergiev Posad-6 has for several years struggled with problems such as dilapidated buildings , lack of central heating , and lack of garbage removal . Sergiev Posad-6 is not "only" a military-biological facility, but also an old Soviet-style closed city that is home to 5,000 to 6,000 residents. In Soviet times, such closed cities were subject to a severe security regime and sometimes did not even appear on maps or road signs. In those times, the inhabitants enjoyed a much higher living standard compared to average Soviet citizens, so it was quite attractive to live there. But those times are long gone. In 2018, a demonstration took place after residents in Sergiev Posad-6 had been without hot water and heating for almost two weeks. As one resident complained : "We have more rats than cats. This is not a town, but some kind of concentration camp."

The residents in Sergiev Posad-6 live in a village called Vaktsina or Settlement 67 , which is kept separate from the technical zone where bioweapons research possibly could be taking place. But basic problems such as mismanagement and corruption must surely have an impact on bioweapons activities. In June 2019, the Moscow City Court sentenced Lieutenant Colonel Vladimir Klevtsov , the former deputy head of the logistics department of the 48th CSRI, to four years in prison and a fine of 780,000 rubles (about $13,000). Klevtsov’s crime was accepting a bribe for services not delivered by a civilian company. In September 2019, the Moscow Regional Court fined Dmitri Shulov , the former chief engineer at the 48th CSRI, 3.2 million rubles (about $53,000) for accepting a bribe. In August 2020, the Solcnechnogorsk Garrison Military Court assessed a fine of 35,000 rubles (some $577) against Dmitry Kutaev , the former deputy head of research work at the 48th CSRI. Kutaev had the previous year signed a certificate for the acceptance of goods, knowing that one of the companies involved did not fulfill its obligations. The resulting damage was estimated to be 416,000 rubles (about $6,900). Kutaev admitted his guilt and provided compensation for the losses incurred.

The most serious corruption scheme involved Sergey Lupin, the former chief accountant of the 48th CSRI, Anton Makeev, the former head of the planning department, Alexei Yakimov, a former employee of the planning department, and Irina Borisova, a former employee of the financial department. From 2009 until 2011, all four forged financial documents and paid themselves more than 21 million rubles (about $345,000). In October 2019, Lupin was sentenced to 4.5 years in prison, Makeev and Borisova to 3.5 years in prison, and Yakimov to 3 years in prison.

According to the Russia-based news outlet PASMI , this particular corruption scheme was only the tip of the iceberg. The scheme began in 2009 and involved Georgy Vasiliev, the head of the Center for Financing Special Programs (later renamed Unit 22280) and two of his employees. The center was formed to pay for special military projects, but Vasiliev abused his authority and the secrecy surrounding the 48th CSRI to transfer money to himself. The scheme lasted until 2014 and resulted in the theft of 355 million rubles (about $5.85 million) or 10 million rubles per month. The subsequent trial punished the persons mentioned above, but several of the major perpetrators involved —including members of the Main Military Prosecutor’s Office and the FSB—escaped punishment.

Overall, it is clear that substantial corruption exists in the administrative and funding support of the 48th CSRI. While the problems described here will not prevent military scientists from researching and producing biological weapons, these deficiencies could affect the quantity and quality of such weapons. They also raise the question of how much of the modernization effort described previously was actually implemented, and how much of the funding was stolen or otherwise misused.

Sergiev Posad-6, previously known as Zagorsk-6, is a closed city where bioweapons research is taking place. Residents of the city are kept out of the technical zone where research is conducted and have protested the living conditions in the town. ( AltGazeta.ru )

The genetic weapons campaign

As mentioned before, the Russian invasion of Ukraine was accompanied by a disinformation campaign alleging US bioweapons activities in Ukraine. The campaign included the claim, made by Major General Igor Kirillov (the head of the Russian NBC Protection troops), that US and German military scientists had been working on a biological weapon capable of selectively targeting different ethnic populations in Russia.

To understand the genesis of this notion, one must go back to the 1930s, when Soviet agricultural scientist Trofim Lysenko—with support from Soviet leader Joseph Stalin—rejected Mendelian genetics and instead advocated the theory that traits acquired through environmental exposures could be transmitted to offspring. [3] This theory effectively destroyed Soviet genetics research and resulted in the execution or imprisonment of thousands of scientists. By the 1960s, it was understood that Lysenkoism was pseudoscience, and it once again became acceptable for Soviet scientists to study genetics.

One reason why the Soviet Union established Biopreparat in the 1970s was because several senior academic scientists, led by Yuri A. Ovchinnikov , convinced General Secretary Leonid Brezhnev that the Soviet biological weapons program should use genetic engineering in order to make new biological weapons. Ovchinnikov was not particularly interested in biological warfare, but he understood how far behind the Soviet Union was in genetic research, and that it would be necessary to have support from the powerful Soviet military to catch up.

This renewed focus on genetics paved the way for Soviet interest in genetic weapons, which preferentially could target people of specific ethnicities or people with specific genotypes. Genetic weapons (sometimes also called ethnic bioweapons) are in that regard different from biological weapons that have been enhanced or modified through genetic engineering. In 1976, Soviet military scientists began to use the term genetic weapon in reaction to suspected military research in the United States. Russian geneticist Evgeny Lilyin recently claimed that Soviet scientists did attempt to make genetic weapons in the 1980s, although apparently without much success.

Following the collapse of the Soviet Union, a strange public "debate" about genetic weapons began in Russia. Senior scientist Mikhail Paltsev and biochemist Alexander Spirin claimed that it would soon be possible to make genetic weapons. Gen. Makhmut Gareev and Maj. Gen. Vladimir Slipchenko discussed the possibility of creating weapons based on new physical principles, including genetic weapons. [4] Both Gareev and Col. Maksimov from Sergiev Posad-6 claimed that such weapons would be outside the scope of international law, including the Biological and Toxin Weapons Convention. Maksimov claimed that the US military was already busy making bioweapons using genetic engineering. During this peculiar and otherwise one-sided "debate," Slipchenko made his opposition to such weapons clear: "Imagine an artillery piece that, having fired a shell at the enemy, immediately explodes, destroying the crew. Would anyone want to fight with such a cannon? Unlikely." According to Slipchenko, even if these weapons proved to be successful they would end up killing as many people as a nuclear war. Genetic weapons were "unmanageable" and only a "complete dilettante" would therefore advocate for the development and use of such weapons, Slipchenko stated.

This was a reference to Yuri Bobylov, who is a chief proponent of genetic weapons in Russia. In his book , The Genetic bomb: Secret scenarios of bioterrorism from 2006 (reprinted in 2008), Bobylov painted a dire picture of the world captured in a Malthusian Trap. Since he described the world as heading towards ecological disaster, he advocated for the development and use of genetic weapons to exterminate most of the human race, leaving only about 1 billion to 1.5 billion people ("the golden billion") to survive and prosper. The term "the golden billion" is widely used in post-Soviet Russia and refers to how a rich and powerful cabal tries to exploit the majority of the human race to benefit the one billion people living in the Western world. The Russian leadership is notorious for using this term and usually portrays itself as fighting against this conspiracy.

In Bobylov’s book and subsequent articles, this term is turned upside down; he encouraged the use of genetic weapons as the main weapon in world genocidal wars to reach the promised land of "the golden billion." Not surprisingly, Bobylov’s book is full of racist sentiments, admiration for Nazism, and respect for individual Nazis like the renowned zoologist Konrad Lorenz. As Bobylov wrote in 2018 : "Military-oriented science reaches the peak of its development when it is the science of life that becomes the science of death and, accordingly, the most important means of war. Civilization on Earth is now in the stage of a deadly crisis. The world urgently needs world genocidal wars for further harmonious development."

What makes Bobylov a remarkable figure is his background and how he was treated. Bobylov had previously worked for several different government agencies and been a staff member of the powerful Military-Industrial Commission (VPK). He knew about the work supervised by Lt. Gen. Valentin Evstigneev , who was the former head of the 15th Directorate of the Soviet General Staff, which was responsible for the Soviet biological weapons program. According to Bobylov, they had a personal conversation in 2007 , in which Evstigneev assured him of the superiority of biological warfare, compared to other methods of warfare. Belye Alvy—a publishing house allegedly controlled by the Russian military, police, and the FSB – was responsible for printing Bobylov’s book . It is therefore safe to say that the Russian government tacitly supported Bobylov’s arguments. In fact, it seems likely that a large part of the Russian "debate" about genetic weapons was a political campaign intended to influence public opinion about biological weapons inside Russia. Since it was exclusively directed at the Russian public, its significance has so far not been properly understood abroad.

Chief-of-Russian-Radiation-Chemical-and-Biological-Protection-Force-Igor-Kirillov

Major General Igor Kirillov is the Chief of the Radiation, Chemical, and Biological Protection Force in Russia. (Jamestown Foundation)

President Putin and the genetic weapon

Russian President Vladimir Putin, left, with Security Council Secretary Nikolai Patrushev at the Kremlin in Moscow, Russia, on June 5, 2017. ( The Kremlin )

In 2007 , the Russian government briefly banned the export of biological material (including hair and blood samples) after the head of the FSB, Nikolai Patrushev, informed President Vladimir Putin that foreign powers were using these samples to develop genetic weapons targeting ethnic groups in Russia. This was the first of many signs regarding a policy shift in response to perceived biological threats. In 2012 , Russia announced it would withdraw from the Cooperative Threat Reduction program, and it completely abandoned the partnership in 2014. Even before that, Russia launched a massive disinformation campaign against the program in neighboring countries, particularly against Ukraine and Georgia. The alleged threat from "US military-biological laboratories" in these countries was subsequently included in the Russian national security strategy in 2015.

In 2012 , Prime Minister Putin (shortly before he returned to the presidency) wrote an essay about future military technologies, including genetic weapons. During a subsequent televised meeting with his ministers, the Russian Defense Minister Anatoly Serdyukov pledged to develop new weapon systems based on Putin’s essay, including genetic weapons. In 2017 , President Putin expressed his concern that certain foreigners (i.e. the US military) were busy collecting biomaterials from ethnic groups in Russia—just as Patrushev had warned 10 years earlier. During his speech at the annual Valdai Discussion Club in 2018, President Putin suggested that foreign scientists were already busy developing genetic weapons.

How people close to President Putin think about this matter is perhaps best explained in a speech by Mikhail Kovalchuk to the Federation Council in September 2015. Kovalchuk is the president of the prestigious National Research Centre Kurchatov Institute and enjoys, together with his brother Yury (known as "Putin's personal banker"), a close relationship with the Russian president. The Kurchatov Institute is famous for its role in the development of nuclear weapons and nuclear energy in Soviet times, but it also provided sanctuary for Soviet geneticists like S. I. Alikhanyan , who lost his job at the Department for Genetics at Moscow State University for opposing Lysenkoism. Alikhanyan would later play a key role in the Soviet biological weapons program and created the State Research Institute of Genetics and Breeding of Industrial Microorganisms in 1968. In 2017, this institute would become a part of the Kurchatov Institute.

In his speech to the Federation Council, Kovalchuk essentially repeated several of the key messages from Bobylov’s book, painting a dire picture of humanity’s future due to population growth and dwindling resources. Unless the human race was brought down to a sustainable level ("the golden billion") it was doomed. If the Russian state was to survive, it therefore had to employ new technology, including genetic engineering. He predicted that it would soon be possible to develop targeted medicine, but also genetic weapons that could strike specific ethnic groups as a weapon of mass destruction. Kovalchuk also warned that the global elite, overseen by the United States, was developing a genetically edited caste of laboring “servant people” who would eat little, not think, and only reproduce on command.

This bizarre and dark worldview may explain a series of government decrees in the 2018-2020 period intended to strengthen the development of genetic technologies in Russia—a program that would have a planned budget of 230 billion rubles (or more than $3.8 billion). The program intends to create three genomic centers and 65 laboratories and research centers, while training some 3,000 individuals. President Putin has compared this effort to the atomic and space projects of the 20th century. Furthermore, a presidential decree in March 2019 prescribed the genetic certification of the population and the formation of a genetic profile of Russians. Kovalchuk’s Kurchatov Institute will provide the scientific leadership for the new program and house a center for digitization and storage of genomic data. A prototype of the biorepository should be ready at the institute in 2024 and overseen by the FSB . The energy company Rosneft will help create a special center capable of decoding the genomes of 100,000 people living in Russia (mostly employees of Rosneft and their family members).

There are competing agendas behind the program, which has some troubling parallels to the decision to create Biopreparat in the 1970s. For President Putin, this program is designed to defend against and presumably also to research and develop genetic weapons. Russian scientists even joked about the fantastical genetic weapons the president likely must have imagined when he agreed to their proposal. President Putin has apparently not been satisfied with whatever research into genetic weapons was undertaken following his essay in 2012 and Defense Minister Serdyukov’s subsequent pledge to develop such weapons. Others—like former education and science minister Andrey Fursenko—hoped to use the program as a belated attempt to catch up with the West in molecular genetics. According to the Russian news aggregation site Meduza , this is badly needed: Russia lacks equipment like DNA sequencers and has only 340 medical geneticists and slightly more than 600 geneticists.

The program could possibly also be viewed as an example of cronyism. It is difficult to ignore that so many of Putin’s associates and friends and even a family member (the president’s eldest daughter Maria Vorontsova is overseeing the program) are involved in the genetics program. One anonymous geneticist quoted by Meduza expressed skepticism regarding the program in sardonic terms: "On the one hand, they want some kind of results, but then they treat science like tractor manufacturing. This country has had this system for the last 20 years. Have you seen it work yet?"

It is also questionable how strong the science behind the Russian fixation on genetic weapons is, and to what extent it instead reflects the rise of pseudo-science in contemporary Russia, which also includes attempts to rehabilitate Lysenko . The possibility of making genetic weapons was first mentioned by Swedish scientist Carl A. Larson in Military Review in 1970. In 1999, the British Medical Association warned that the biotechnological revolution and projects like the Human Genome Project could create a breakthrough for the development of such weapons. Since then it has only become clearer how challenging this would be. As a recent US report made it clear, it would be very hard to make such a weapon, although future technological changes could yet alter this assessment. The Russian scientist Valery Ilyinsky, the founder of the DNA testing company Genotek, called the idea of genetic weapons an "utter absurdity" and "the stuff of science fiction movies." Russian scientist Mikhail Gelfand completely dismissed the possibility of genetic weapons : "It is probably possible—although very expensive and very difficult—to create a weapon against some very small ethnic group that has not mixed with anyone for the last thousand years. The Russians are not such an ethnic group."

At the very minimum, President Putin’s interest in genetic weapons and more generally gene technology suggest a commitment to a new generation of biological weapons. Although the Russian government undoubtedly would portray this as a defensive response, one cannot ignore the possibility that the Russian government would attempt to develop its own genetic weapons. At the same time, the dubious science behind genetic weapons and the poor state of Russian biotechnology makes it unlikely that Russian scientists will quickly achieve a breakthrough in this field.

Mikhail Kovalchuk delivers a speech at the Federation Council in 2015, where he espouses "the golden billion", a conspiracy theory that posits that the human population must be reduced to one billion people globally. ( TRV-Science.ru )

The threat from Russian biological weapons

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Meeting between Russian President Vladimir Putin and his French counterpart Emmanuel Macron, in Moscow, on February 7, 2022. ( Elysée )

In a last-ditch attempt to avert a Russian invasion of Ukraine, French president Emmanuel Macron visited President Putin in Moscow in February 2022. Their meeting took place at a very long table in the Kremlin, because President Macron had refused to take a COVID-19 test before meeting his Russian counterpart. Macron’s motive for refusing a Russian PCR test was telling: He did not want Russian intelligence to get a sample of his DNA.

This episode once again raises the question whether Russia still has an offensive biological weapons program. The short answer to that question is: yes. Although there is no definitive proof—nor should one expect such proof from the current Russian government—there are numerous public indications that suggest that Russia has maintained and modernized the surviving parts of the Soviet biological weapons program. The indications include, but are not limited to, the Russian government’s repeated admission and subsequent, repeated denials that it had inherited a large part of the Soviet biological weapons program; press and other public accounts of continuing research into biological weapons (including non-lethal biological weapons); and the Russian pursuit of a disinformation campaign that is directed against the Cooperative Threat Reduction program and attempts to characterize it as a US bioweapons effort. Meanwhile, the "debate" and policy decisions regarding genetic weapons demonstrate that the Russian leadership is obsessed with the idea of a new generation of advanced bioweapons.

It needs to be stressed that thanks to years of relentless Russian state-sponsored propaganda, many Russians take it for granted that the US military has an offensive biological weapons program. According to a recent Russian survey , 84.4 percent of Russians have heard about a US biological weapons program in Ukraine and 66.5 percent believe that bioweapons were being developed there. Russian virologist and professor Alexander Chepurnov used this disinformation to call for reinvigorating the Russian biological weapons program in order to deter the Americans: "And here it is important to understand that the study of biological weapons is necessary not only in order to fend off the looming biological threats over our country, but also so that the counterthreat deters those who want to use it."

While all of this is concerning, this assessment of the Russian bioweapons program must be accompanied by several caveats. The backward nature of Russian biotechnology, poor management, brain drain (accelerated by the Russia-Ukraine War), and corruption will all impede both the quality and quantity of any Russian bioweapons research. While the Russian preoccupation with genetic weapons is deeply disturbing, it is unclear how Russian scientists—or anybody else, for that matter—can ever develop a weapon which can kill Swedes but not Germans, or Arabs but not Israelis, etc. The Russian genetic weapons campaign bears all the hallmarks of pseudo-science, not unlike Lysenkoism.

The Russia-Ukraine War could facilitate the Russian military to address these issues. Most likely, the Russian military is right now searching for weapons that can turn the tide of war on the battlefield in Ukraine and that might also prove useful in a wider war against NATO. As professor Chepurnov warned , Russia will "need to solve a lot of things and quickly so as not to be naked in this war." That would mean curbing problems like corruption in the 48th CSRI. The war might also force the Russian leadership to take a new look at genetic weapons and search for more realistic solutions. Even if genetic weapons are a dead-end, there are plenty of ways in which genetic engineering can be used to enhance existing bioweapons or develop entirely new ones. If nothing else, the last 30 years since the fall of the Soviet Union has demonstrated that the Russian government never abandoned the belief that biological weapons could play an important role in future warfare. It would be very foolish to ignore this belief and the threat it poses.

Robert Petersen , MA in History and Middle East Studies, PhD in history, is an analyst at the Centre for Biosecurity and Biopreparedness (CBB) in Denmark. He works with open source intelligence, the history of biological weapons and biological warfare as well as regulatory aspects of biosecurity in Denmark.

[1] Allison Puccioni: "Facility analysis: Sverdlovsk-19". Jane's by IHS Markit, October 20 2017.

[2] All the articles are scientific publications and the majority are available on the website of the journal "Problems of Particularly Dangerous Infections", which is being published by Federal State Scientific Institution “Russian Research Anti-Plague Institute “Microbe” .

[3] To understand the difference between Lysenkoism and the modern studies in epigenetics, please read "Russia’s new Lysenkoism" by Edouard I. Kolchinsky et al .

[4] Vladimir Slipchenko’s book, Sixth Generation Wars: Weapons and Military Art of the Future , is available for free online but requires browser-based translation software to read in English.

So sad that The Bulletin is pushing anti Russia propaganda. The sensational title: ” Fear and Loathing in Moscow” undermines the scientific credibility essential for The Bulletin to be taken as a objective source of information. The failure to report on NATO or US bio weapons further weakens The Bulletin’s credibility. I will no longer support The Bulletin. This one sided propaganda increases the probability of nuclear war therefore The Bulletin has become worse then nothing. I have no love for the Russian government just a commitment to dispassionately reduce the probability of nuclear war. Retract the sensational propaganda and … Read more »

russian belief in the plausibility of a genetic weapon, regardless of its effectiveness on a target population, could still result in death, disease and disability in large numbers of people if it were ever used. the results would just be seen in a much larger group than the target population. given their denial of other incidents, it is unlikely they would ever admit to the use of such a weapon and depending on the effects, it might take some time if ever to figure out what had happened. the amount of current genetic knowledge is infinitesimal compared to what is … Read more »

I am overwhelmed by my fear, I had nothing to say. . . . ????????

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Continuing Education Activity

Bioterrorism involves the deliberate release of bioweapons to cause death or disease in humans, animals, or plants. Biological weapons may be developed or used as part of a government policy in biological warfare or by terrorist groups or criminals. Biological weapons can initiate large-scale epidemics with an unparalleled lethality, and nation-states and terrorist groups have used dangerous and destructive Biological weapons in the past. This activity reviews the types, evaluation, and treatment of different biological weapons that have been used and has the potential to be used in bioterrorism attacks and discusses the role of the inter-professional team in evaluating and treating catastrophic events associated with bioterrorism.

Explain the definition of bioterrorism.
Review the types of commonly used as well as potential bioweapons.
Explain why health professionals need to be up to date in the workup and treatment of biological weapon-based attacks.
Describe the types of bioterrorism events and discuss the role of the inter-professional team in evaluating and treating the victims of a potential bioterrorism attack.
Introduction

Biological weapons are devices or agents used or intended to be used in a deliberate attempt to disseminate disease-producing organisms or toxins using aerosol, food, water, or insect vectors. Their mechanism of action tends to be broadly through infection or intoxication. [1] Bioterrorism involves the deliberate release of bioweapons to cause death or disease in humans, animals, or plants. These biological agents can include bacteria, viruses, toxins, or fungi. [2]

Biological weapons may be developed or used as part of a government policy in biological warfare or by terrorist groups or criminals. Biological weapons can initiate large-scale epidemics with an unparalleled lethality, and nation-states and terrorist groups have used dangerous and destructive biological weapons in the past. [1] The degree of the potential damage, coupled with the unpredictable nature of these agents, has led to an increased interest by numerous countries, including the United States, in drawing up policies and guidelines in the event of such an attack to be prepared.

Keeping in mind the horrific nature of these agents, the Geneva protocol, first signed in 1925, and currently signed by 65 out of 121 country states, prohibited the development, production, and use of biological weapons in war. [3] However, not being country states, biological weapons to wage bioterrorism tend to be a relatively common choice for terrorist organizations. The relative ease with which the agents may be deployed, the devastating effects on the victims, and their inexpensive nature make them all more lucrative to these organizations. However, the unpredictable nature of these biological weapons means that they may affect both the intended victims and inadvertently affect friendly forces. Despite this drawback, terrorist organizations favor the use of biological weapons. [2]

Healthcare professionals need to be aware of the essentials of bioterrorism and biological weapons, as these may be used as part of a terrorist attack in any part of the world. Thus, healthcare professionals need to be trained and prepared in case of a potentially catastrophic event, where quick action and decision-making may potentially save lives. This article reviews the previous incidents of biological terrorism, types of biological weapons, evaluation of patients exposed to potential biological weapons, and treatment of patients who have been potentially exposed to the various commonly employed biological weapons. This article also aims to discuss an inter-professional team's role in evaluating and managing a bioterrorism attack. For this activity, bioterrorism's biological weapons have been broadly classified under four major headings, including bacterial agents, viral agents, fungal agents, protozoal agents, and toxins.

The Centers for Disease Control and Prevention (CDC) have classified biological weapons into three categories based on various factors, including the morbidity and mortality caused by the disease in humans: [2]

Category A: Highest priority. Pose a risk to national security. They are easily transmitted from person to person and have high morbidity and mortality. They would have a major public health impact, cause panic, and result in special public health preparedness requirements.
Category B: Second highest priority. These include diseases with lower morbidity and mortality as compared to category A. They are also more difficult to disseminate.
Category C: Third highest priority. They have the potential to cause significant morbidity and mortality but consist mostly of emerging pathogens that could potentially be engineered for mass dispersion in the future.

For the purpose of this review, the biological weapons and agents which can be used in bioterrorism have been broadly classified as bacterial, viral, fungal, protozoal, and toxins. A brief overview of specific agents which have been used in prior attacks as well as have the potential to weaponized are discussed in this review. The agents being discussed are summarized below: [1] [4] [5]

Bacterial: Bacillus anthracis (anthrax), Brucella species (brucellosis), Burkholderia mallei (glanders), Burkholderia pseudomallei (melioidosis), Franciscella tularensis (tularemia), Salmonella typhi (typhoid fever), and other Salmonella species (Salmonellosis), Shigella species (shigellosis), Vibrio cholerae (cholera), Yersinia pestis (plague), Rickettsial agents including Coxiella burnetii (Q fever), Rickettsia prowazekii (typhus fever), Rickettsia rickettsii (Rocky Mountain spotted fever), and Chlamydia psittaci (Psittacosis) .
Viral: Variola major (Smallpox), viral hemorrhagic fevers, viral encephalitis.
Fungal : Coccidiodes immitis (coccidioidomycosis), Histoplasma capsulatum (histoplasmosis).
Protozoal: Cryptosporidium parvum (Cryptosporidiosis).
Toxins: ricin, abrin, Clostridium perfringens toxins , Clostridium botulinum toxins, tetrodotoxin, nerve agents
Issues of Concern

There have been numerous incidents in the past where bioweapons were used in biowarfare. The intentional use of biological weapons, including infectious agents during the war, led to a new and yet unknown threat. The initial and early attempts at using biological weapons in warfare date to the middle ages and included crude methods such as using cadavers and carcasses of humans and animals to contaminate water sources of enemy armies and enemy civilians during warfare. [1]

One of the first reported instances of biological weapon use was as early as 600 BC. Solon used a purgative herb called hellebore during the siege of Krissa. [4] The ingestion of white hellebore (Veratrum Album L.) has been reported to cause nausea, vomiting, abdominal pain, bradycardia, and hypotension, with complete atrioventricular block reports in one patient who had accidental ingestion. [6]

In 1155 AD, in Tortona, Italy, Emperor Barbarossa poisoned wells with human bodies. In 1346, the Tatar forces who were laying siege to the city of Kaffa (presently Feodosia, Ukraine) engaged in biological warfare by employing the use of catapulting people suffering from the bubonic plague over the walls of the city to initiate a bubonic plague epidemic in its inhabitants and weaken them. [1] [4] [7] This led to a bubonic plague outbreak followed by a retreat of the defending army and the subsequent conquest of Kaffa by the Tatars. Following this, ships carrying possibly bubonic plague-infected people and vectors (rats) sailed to Genoa, Constantinople, Venice, and other Mediterranean ports. This is thought to have directly contributed to the second plague pandemic, outlining the sheer destructive and unpredictable nature of biological weapons leading to unintended widespread disease. [8] In 1495, in Naples, Italy, the Spaniards mixed wine with blood from leprosy patients to sell to their French foes. [4] In 1710, similar to the events of 1346, Russian troops catapulted the bodies of bubonic plague victims into Swedish cities. [4]

In the 18th century, smallpox was a popular choice for biological weapons. [7] During the French and Indian War between 1754 to 1767, the commander of British forces in North America, Sir Jeffrey Amherst, employed the deliberate use of smallpox to "reduce" the populations of the Native American tribes who were hostile to the British. [7] A naturally occurring smallpox outbreak at Fort Pitt helped the British troops execute Amherst's plan by virtue of the generation of smallpox-laden fomites. In 1763, one of Amherst's subordinates, Captain Ecuyer, gave the Native Americans a handkerchief and a few blankets taken from the smallpox hospital. This resulted in an epidemic among the Native American tribes. [7] In 1797, Napoleon flooded the plains around Mantua in Italy to increase the spread of malaria. In the United States, in 1863, the Confederates sold clothing obtained from patients suffering from yellow fever and smallpox to Union troops during the Civil War. [4]

More recently, in the 20th century, biological weapons were reportedly used to a limited extent. Some evidence suggests that during World War I, Germany had developed a biological warfare program that planned on covert operations to infect the livestock and contaminate the animal feed, which was to be exported to the Allied forces from neutral countries. Reports circulated of attempts to ship cattle and horses inoculated with Bacillus anthracis (causing anthrax) and Burkholderia mallei (causing glanders) to the United States and other countries. [1] [4] These same organisms were also used to infect Romanian sheep, which were planned to be exported to Russia. There were also other allegations of attempts to spread the plague in Russia and cholera in Italy. Germany denied all such allegations of indulging in biological warfare. However, following these allegations, keeping in mind the horrific and unpredictable nature of these agents, the Geneva Protocol was signed in 1925, which prohibited the development, production, and use of Biological weapons in war. [3]

During World War II, there were once again attempts made by various nation-states to indulge in the use of biological weapons. [1] Japan engaged in research related to biological weapons from 1932 until the end of World War II. The agents of interest to the Japanese biological weapons program included Bacillus anthracis, Vibrio cholerae, Shigella spp, Neisseria meningitidis, and Yersinia pestis . Between 1932 and 1945, more than 10,000 prisoners died due to experimental infection as part of this biological weapons research. A majority of these prisoners’ deaths were a direct consequence of experimental inoculation of biological weapons and pathogens, which caused anthrax, cholera, meningococcal infection, dysentery, plague, and so on. Research on tetrodotoxin (an extremely potent toxin derived from the ‘fugu’ fish) was conducted. [4] [5]

Prisoners in Nazi concentration camps in Germany were deliberately infected with Rickettsia prowazekii , Plasmodium species, and hepatitis A virus to be treated with experimental drugs and vaccines. [7] In England, experiments involving weaponized spores of Bacillus anthracis were conducted off Scotland's coast, which resulted in heavy contamination. Still, viable anthrax spores remained on the island until it was decontaminated with formaldehyde and seawater in 1986.

In 1942, the United States initiated a biological warfare program. The program included research on B. anthracis and Brucella suis in various research facilities, including a development facility at Camp Detrick in Maryland, known today as the US Army Medical Research Institute of Infectious Diseases (USAMRIID). About 5000 bombs containing B. anthracis spores were developed at Camp Detrick, but since the facility lacked adequate safety measures, further production during World War II was stopped. [4] [7]

Post World War II, various other nation-states and organizations dabbled in developing biological weapons. By the 1960s, the United States military developed a large biological weapons arsenal that consisted of various biological pathogens, toxins, and fungal plant pathogens that could induce crop failure and result in subsequent famines. In 1972, a United States-based extremist group called themselves ‘Order of the Rising Sun’ was found to possess typhoid bacteria cultures intended to disseminate the water supplies of numerous major mid-western cities.

In 1978, a Bulgarian exile, Georgi Markov, was assassinated in London in what later came to be known as the “umbrella killing” due to the murder weapon being a device hidden inside an umbrella. A tiny pellet was discharged into Markov’s leg at a bus stop in London. The next day, he became severely ill and died 3 days after the incident. 10 days before Markov’s assassination, an attempted assassination had occurred in Paris, France. Another Bulgarian exile, Vladimir Kostov, felt a sharp pain in his back in a metro stop in Paris. He reported seeing a man carrying an umbrella fleeing the scene. Two weeks later, after learning of Markov's assassination, Kostov was examined by a French medical team, and they extracted a similar pellet. It was made out of an alloy of platinum and iridium and contained the plant toxin ricin (made from castor beans).

In 1979, there was an outbreak of anthrax in the Russian city of Sverdlovsk (now Yekaterinburg). The outbreak occurred in people close to a Soviet military microbiology facility (called Compound 19). As well as humans, livestock in the area also died of anthrax. The unintentional release of anthrax spores was thought to have resulted in a total of 66. [9] In 1980, the Baader-Meinhof group (also called the Red army faction) in Germany was found to have access to Clostridium botulinum cultures as well as to a biological laboratory. [1] In 1986, the Rajneesh cult in Dalles, United States, contaminated salad bars in local restaurants with a resulting 751 cases. The cult was attempting to prevent citizens from voting in an upcoming election. [1] [10]

From 1990 to 1994, a Japanese religious cult calling themselves Aum Shinrikyo (presently called Aleph) made nine failed attempts to release anthrax spores as well as an aerosol containing botulinum toxin in Tokyo with the intent to murder innocent civilians. [1] However, in 1995, they succeeded in releasing a nerve gas called sarin in Tokyo’s subway system, which resulted in the death of 12 people and injury to approximately 3,800 people. [9]

In 2001 in the United States, a series of letters containing anthrax spores were mailed to senators, journalists, and media buildings. There were 5 casualties and 22 people who were seriously injured. A large-scale investigation finally implicated a former United States scientist as the perpetrator. [3] Using letters in the post as a mode of delivery of biological weapons remains a popular choice among bioterrorists. There were more than 20 attacks involving ricin between 1990 to 2011. Due to the highly destructive nature of biological weapons and the relative ease with which they may be produced, they remain a big threat.

Specific Biological Weapons

Bacterial Agents

Bacillus anthracis (Anthrax)

Bacillus anthracis is an aerobic or facultatively-anaerobic, encapsulated, gram-positive or gram-variable, spore-forming bacilli that grow well on blood agar in the form of large, irregular-shaped colonies. The word anthrax originates from "anthrakis" in Greek, meaning black, which refers to the necrotic lesions which are encountered in cutaneous anthrax. B. anthracis is categorized as a ‘category A’ priority organism by the Centers for Disease Control and Prevention due to its potential capability to be disseminated as a bioweapon. [2]

The pathogenesis of anthrax infections depend on the route of inoculation, with three routes reported in humans: Inhalational anthrax by the accumulation of B. anthracis spores initially in the lung alveoli followed by transport to the regional lymph nodes where it germinates, multiplies, and begins toxin production with subsequent systemic illness, bloodstream infection and septic shock. Cutaneous anthrax occurs by the inoculation of anthrax spores through a break in the skin into the subcutaneous tissues. B. anthracis germinates and multiplies locally along with toxin production, which causes the characteristic edema as well as cutaneous ulceration. Gastrointestinal anthrax occurs due to ingestion of meat contaminated with anthrax spores, leading to mucosal ulceration and bleeding. Another fourth form of anthrax has been reported recently in northern European intravenous drug users due to the use of contaminated needles, producing lesions at the injection site clinically similar to cutaneous anthrax but can also present with a deeper infection including myositis. [11]

Symptoms and Signs [11]

Inhalational anthrax has an incubation period of around 1 to 6 days following exposure. It presents with a non-specific prodromal phase, including fever, malaise, nausea, vomiting, chest pain, and cough. The second stage of bacterial replication follows this in the mediastinal lymph nodes, which causes hemorrhagic lymphadenitis and mediastinitis, with subsequent progression to bacteremia. Meningitis can occur in up to 50% of cases. Death can result, ranging from 1 to 10 days after symptom onset.

Gastro-intestinal can have oropharyngeal and/or intestinal involvement. In oropharyngeal anthrax, ulcers may develop on the posterior oropharynx, which can cause dysphagia and regional lymphadenopathy. In intestinal anthrax, patients may have fever, nausea, vomiting, and diarrhea. They can also have acute abdomen-like features with associated hematemesis, bloody diarrhea, and massive ascites. Untreated patients can progress to septicemia with a mortality range of 25% to 60%.

Cutaneous anthrax, which is also called hide-porter's disease , can present one to 10 days following exposure with a pruritic and papular lesion which can progress over days into a painless ulcer. The primary lesion can have associated satellite vesicles that can progress to a necrotic center with non-pitting edema surrounding it. A painlessness lesion is considered characteristic of cutaneous anthrax. The eschar may dry and slough off in about 1 to 2 weeks, but the mortality rate can approach nearly 20% without treatment.

Investigations and Management [11]

The CDC recommends using PCR, gram stain, and bacterial cultures depending on clinical features from blood, pleural fluid, ulcer, cerebrospinal fluid, or stool. Routine diagnostic tests, including a complete blood count and chest x-ray, are also recommended. Chest X-ray in inhalational anthrax can show an enlarged mediastinum. A CT scan shows enlarged hilar lymph nodes, evidence of mediastinal hemorrhage or pleural effusions. Cutaneous anthrax may be diagnosed using a methylene blue stain that can show a non-motile gram-positive bacillus.

The laboratory personnel must be adequately warned about the possibility of anthrax. All inhalational anthrax cases should be considered as a bioterrorism event, and decontamination is done appropriately. Anthrax is reportable and, if identified, should be immediately reported to local authorities and the CDC.

Treatment for inhalational anthrax involves a regimen using one bactericidal agent + one protein-synthesis inhibitor drug. Intravenous ciprofloxacin + clindamycin/linezolid is the preferred regimen. In meningitis, a three-drug regimen is preferred with the addition of a bactericidal agent from a different drug class, such as a beta-lactam. In cutaneous lesions, oral ciprofloxacin/doxycycline is effective, however with extensive edema or in cases of head and neck involvement, an intravenous multi-drug regimen is preferred. An antitoxin may be recommended along with the multi-drug regimen. Treatment with Anthrax immune globulin is added on for systemic treatment. Anthrax vaccine may be considered for exposed people following a bioterrorism event. In the event of inhalation exposure, should undergo prophylactic treatment for 60 days, regardless of vaccination. A combination of doxycycline and ciprofloxacin is the recommended first-line therapy in post-exposure prophylaxis.

Importance in Bioterrorism [3]

Anthrax has been used in bioterrorist attacks in the past, with the most prolific example being the ‘Anthrax letter’ attacks in the United States in 2001. It is a category A priority pathogen as per the CDC. It is highly stable in aerosolized form, making it one of the most popular biological weapons choices.

Brucella species (Brucellosis)

In humans, Brucellosis may be caused by four different species, including B. suis, B. abortus, B. melitensis, and B. canis. Brucella species are gram-negative, non-motile Cocco-bacilli, which are facultatively intracellular and do not form spores or toxins. [12]

Symptoms and Signs [12]

Brucellosis can present with clinical features based on the underlying clinical syndrome, potentially including features of meningoencephalitis, myelitis, transaminitis, orchitis, epididymitis, endocarditis, sacroiliitis, spondylodiscitis, osteomyelitis, septic arthritis, epidural abscesses, and hepatic abscesses. Respiratory symptoms can include a cough, breathlessness, and pleurisy, with the presence of focal lung abscesses and pleural effusions having been reported. Guillain-Barre syndrome and Subarachnoid hemorrhage have been reported in acute neurobrucellosis. Dermatological manifestations include maculopapular rashes, erythema nodosum, cutaneous abscesses, and panniculitis. Endocarditis and aortic fistulas can rarely occur. Although lymphadenopathy, hepatomegaly, splenomegaly, and clinical features of an underlying clinical syndrome may be found, the physical examination may be normal. Brucellosis frequently presents as a fever of unknown origin, prompting significant workup before a diagnosis is reached. The mortality rate ranges from two to five percent.

Investigations and Management [12]

Patients may have anemia, leukopenia, or even pancytopenia along with elevated inflammatory markers, serum lactate dehydrogenase, transaminases, and alkaline phosphatase. In spondylitis, disc space narrowing, sclerosis, and bone destruction may be visible on imaging. On liver biopsy, granulomas may be observed. Blood cultures on tryptose medium may yield growth of Brucella, but due to its slow-growing nature, it may take more than a week. Bone marrow cultures have a higher yield when compared to blood cultures. In endemic areas, standard agglutination tests are commonly used. ELISA or Rose Bengal plate agglutination test also may be used. Doxycycline, along with another agent, which may be streptomycin, gentamicin, rifampin, or co-trimoxazole, is the mainstay of treatment. As Brucella is an intracellular organism, several weeks of treatment may be necessary. Monotherapy should be avoided due to high relapse rates. A regimen of co-trimoxazole plus rifampin for four to six weeks may be used in the pediatric population. Rifampin is used during pregnancy, with co-trimoxazole added postpartum. Surgical debridement may be required in certain cases, especially in fistulas and bone involvement.

Importance in Bioterrorism

Brucella has been successfully engineered as a biological weapon by the United States and several other countries, although it has never been used during the war. Brucella can be easily aerosolized, and it survives well in the aerosol form. In a bioterrorist event using Brucella , treatment remains the same as for naturally occurring Brucella infections as detailed above. The relatively lower mortality rate of Brucellosis has led to it falling out of favor as a potential bioweapon and has more historical significance. [12] [13]

Burkholderia mallei (glanders) and Burkholderia pseudomallei (melioidosis)

Glanders is caused by Burkholderia mallei which is a gram-negative, aerobic, non-motile bacillus. Melioidosis is caused by Burkholderia pseudomallei, which is also a gram-negative, aerobic bacillus but is motile. These two bacteria are related closely and can both present with the disease in humans. [14]

Symptoms and Signs

The incubation period for glanders ranges between one to 21 days but can even be months to years. Glanders usually starts as fever, followed by pustules, abscesses, and pneumonia. Acute glanders is usually fatal within seven to ten days of onset. Chronic glanders causes death within months, and the survivors become carriers. [14]

Burkholderia pseudomallei can enter the human host through three modes: ingestion, inhalation, or direct inoculation. The incubation period of melioidosis is highly variable. It can range from two days to several years. Acute melioidosis presents with fever, cough, pleurisy, myalgia, arthralgia, headache, night sweats, and anorexia. Liver, spleen, prostate, and parotid abscesses are common. In about 10% of cases, symptoms last more than 2 months, which constitutes Chronic melioidosis. Direct inoculation through wounds in the body and the organism's ability to use an axoplasmic transport mechanism to invade the central nervous system using the peripheral nervous system results in neuromelioidosis, which is notoriously difficult to diagnose as well as a treat. [14] [15]

Investigations and Management

Cultures can diagnose both organisms. In melioidosis, blood, sputum, urine, and throat swab cultures may be indicated. It is recommended to perform the laboratory work on these organisms under BSL-3 precautions. Latex agglutination, indirect hemagglutination, and direct immunofluorescence tests may be available based on region. Patients may have non-specific anemia, leukopenia or leukocytosis, and elevated inflammatory markers. Imaging of appropriate body sections based on clinical presentation may reveal abscesses which can point towards melioidosis. Histopathology of affected tissue may show granulomas. [14] [15]

In both diseases, patients with significant lungs' significant involvement can progress to respiratory failure and require mechanical ventilation. Sepsis may also occur. In glanders, the recommended treatment regimen includes imipenem and doxycycline for two weeks, which should be followed by doxycycline and azithromycin for six months. A post-treatment CT can show improvement of underlying abscesses. Glanders tends to be fatal in 95% of cases without appropriate treatment, and death can occur within seven to ten days of onset. Mortality may still be as high as 50%, even with appropriate antibiotic treatment. [14]

The mortality in melioidosis ranges between 20% to 50%. [16] This can exceed 90% in sepsis, but it may decrease to 10% in uncomplicated cases with appropriate antibiotic therapy. [14] The recommended treatment regimen in acute melioidosis includes intravenous ceftazidime. Carbapenems, including meropenem and imipenem, are also effective. Like glanders, patients undergo treatment with intravenous antibiotics for two weeks, followed by doxycycline and co-trimoxazole for up to 20 weeks to eradicate the disease. Most abscesses often resolve with antibiotic therapy, but some may require surgical debridement. There may be a recurrence in 20% of cases, but this is reduced to less than five percent with co-trimoxazole eradication therapy. Due to the risk of relapse, lifelong follow-up may be required. No vaccines or approved antibiotic prophylaxis regimens are currently available for melioidosis or glanders. [14]

As per the CDC, both B. pseudomallei and mallei are category B bioweapons. During World War I, German sympathizers in numerous countries infected horses meant for dispatch to conflict areas with B. mallei to induce glanders. This led to the combat operations being affected due to the infection of humans and horses. Japan and the Soviet Union researched the use of B. mallei before World War II. The Japanese deliberately infected Chinese prisoners using B. mallei . Numerous countries, including the United States, studied B. pseudomallei for its potential use as a bioweapon. However, there have not been any reports of the malicious use of B. pseudomallei or B. mallei in recent years. [17]

Franciscella tularensis (tularemia) [18]

Francisella tularensis is a highly infectious gram-negative coccobacillus. Infection can occur through various entry points, including inhalation, direct contact with a break in the skin or mucous membranes, ingestion, or through ticks or fly vectors.

Symptoms and Signs [19]

F. tularensis infections can cause distinct clinical syndromes based on the mode of exposure. Percutaneous inoculation usually causes ulceroglandular tularemia, which is characterized by a cutaneous ulcer at the inoculation site as well as tender regional lymphadenopathy. Inhalation can result in primary pneumonia. Ingestion can cause oropharyngeal disease, which consists of tonsillitis or pharyngitis with associated cervical lymphadenopathy. Other presentations of tularemia can include oculoglandular and typhoidal (pyrexia without a localizing sign). Mortality is ranges between 2 to 24% depending on the strain, with certain strains such as the type A strain being more lethal.

Investigations and Management: [19]

Tularemia requires a high index of clinical suspicion as laboratory identification is difficult. Patients may have raised inflammatory markers or leukocytosis. The cornerstone of laboratory diagnosis relies on the serologic diagnosis. An initial titer of more than 1:160 or a four-fold increase in titers between the initial and convalescent samples indicates a diagnosis of tularemia. Early testing may yield negative results as antibodies take time to form. Hence, a negative serology early on does not rule out Tularemia. Cultures of blood, CSF, lymphatic tissue, and ulcer swabs may yield the growth of F. tularensis. However, it is important to note that culturing should be attempted only in highly controlled settings as lab workers' accidental inhalation can potentially cause pneumonic tularemia. The culture of F. tularensis also requires specialized culture media and longer incubation. On other laboratory evaluations.

The recommended treatment regimen for tularemia consists of intravenous gentamicin for seven to 14 days. Fluoroquinolones such as ciprofloxacin also have a role in mild disease, but data of its use in the more virulent type A infections is limited. Bacteriostatic agents like tetracyclines should be avoided due to the high risk of relapse. Incision and drainage of the affected lymph nodes are indicated in select cases.

Importance in Bioterrorism [19]

F. tularensis has been designated as a category A agent due to a low infectious dose, its ability to aerosolize, and its history of being developed as a biological weapon.

Salmonella typhi (typhoid fever) and other Salmonella species (Salmonellosis)

Salmonella typhi is a gram-negative, flagellated bacillus that causes typhoid fever. It is usually contracted by ingesting contaminated water or food with an infectious dose ranging between 1000 and 1 million bacteria. Salmonella typhi can enter the small intestine submucosal layer by direct penetration into the epithelial tissue, following which it causes hypertrophy of the Peyer’s patches. It then disseminates through the lymphatics and the bloodstream. [20]

Salmonella genus is motile, gram-negative, produces hydrogen sulfide, acid-labile, and facultative intracellular bacteria that belong to the Enterobacteriaceae family. [21]

In Typhoid fever, the incubation period ranges between seven to 14 days after initial inoculation. Following this, patients can present with fever and abdominal symptoms, including abdominal pain, nausea, vomiting, diarrhea, or constipation. A stepladder pattern of fever and relative bradycardia is classically associated with typhoid and enteric fever. [20] [22] Hepatomegaly and splenomegaly can develop during disease progression. Rose spots, which are blanching erythematous maculopapular rashes consisting of lesions that are two to four mm in diameter, can develop on the abdomen and chest. [20]

Other Salmonella infections can present with bacteremia or as focal infections, including gastroenteritis, meningitis, osteomyelitis, and urinary tract infections. [21]

In Typhoid fever, a blood count can show either leukopenia or leukocytosis with a left shift. Relative anemia could be seen. Blood and stool cultures are recommended in the workup. Blood cultures may be positive in 40 to 80% of patients, while stool cultures could be positive in 30% to 40%. The most sensitive test remains a bone marrow aspirate for culture, with more than 90% being positive for Salmonella typhi. Widal test is a measure of agglutinating antibodies against the flagellar H and lipopolysaccharide O antigens. A positive Widal constitutes a four-fold increase in the antibody titers when taken 10 days apart. Currently, ciprofloxacin or ofloxacin is the mainstay of treatment in non-endemic regions. In endemic areas, and when resistance to quinolones is suspected, an extended-spectrum cephalosporin like ceftriaxone should be used with or without azithromycin based on local guidelines and resistance patterns. Approximately around 1% to 5% of patients can become chronic carriers of Salmonella typhi despite appropriate antimicrobial therapy. [20]

For other Salmonella infections, the gold standard test for diagnosis is bacterial culture. Stool, blood, urine, bile, CSF, and bone marrow may be cultured based on the clinical syndrome. Due to the production of hydrogen sulfide, Salmonella forms black colonies on Hektoen Agar. PCR for specific Salmonella species is also commercially available and is being increasingly used in clinical medicine. [21]

Importance in Bioterrorism [23]

Salmonella is a category B bioweapon as per the CDC. It has been used in biowarfare by the Germans during World War I and in the infamous attack by the Rajneesh cult in Dallas, TX in the United States in 1986, where they contaminated salad bars in local restaurants with Salmonella to influence an upcoming election.

Shigella species (shigellosis) and Escherichia coli O157:H7

Shigella is a gram-negative, non-motile, facultatively anaerobic, and non-spore-forming bacillus which has 4 serotypes, including serotype A ( Shigella dysenteriae with 12 serotypes), serotype B ( Shigella flexneri with 6 serotypes), serotype C ( Shigella boydii with 23 serotypes), and serotype D ( Shigella soneii with 1 serotype). Transmission occurs mainly via the fecal-oral route and maybe water or food-borne. The number of organisms required to cause illness is usually only 10 to 200 bacteria. It produces enterotoxin one and two, which causes Shigella -associated diarrhea and is responsible for cytotoxicity and complications such as hemolytic uremic syndrome. [24]

Escherichia coli O157: H7 is a Shiga-like toxin-producing strain that is a food and waterborne pathogen. It is a gram-negative bacillus and belongs to the Enterobacteriaceae family. Naturally occurring infections occur through the fecal-oral route by consumption of contaminated food and water. Only a relatively low inoculum (102 CFU) is required to cause infection. [25]

Shigellosis can present with abdominal discomfort or severe diffuse colicky abdominal pain. There can be mucoid diarrhea that can precede dysentery. Fever, nausea, vomiting, lethargy, anorexia, and tenesmus are also common. Physical examination may indicate lethargic or toxic patients with fever and altered vital signs. An abdominal examination can show a distended abdomen with tenderness in the lower abdomen because of the sigmoid colon and rectum's involvement. [24]

In E. coli O157: H7 infections, patients present with acute onset bloody diarrhea and abdominal cramping with or without fever. There may also be nausea, vomiting, and profuse diarrhea resulting in dehydration and decreased urine output. Abdominal tenderness may be elicited by virtue of Shiga-like toxin-induced intestinal inflammation. Systemic signs of dehydration may be present. [26]

In shigellosis, a complete blood count can show leukocytosis with a shift to the left or leukopenia. Anemia and/or thrombocytopenia may be present. Inflammatory markers may be raised. Stool analysis can show fecal leukocytes and red blood cells. A stool culture can yield the growth of Shigella . Blood cultures may be positive in complicated cases. There may be a mild elevation of bilirubin and creatinine. Electrolytes may be deranged with hyponatremia and hypokalemia. ELISA can be used to detect S. dysenteriae type-1 toxin in the stool. PCR can be used to identify virulent genes such as ipaH, virF, and virA genes. The mainstay shigellosis treatment involves hydration and electrolyte management. In adults, empiric antibiotic therapy is based on resistance patterns. Fluoroquinolones are recommended when there are no risk factors for resistance. A third-generation cephalosporin is recommended when resistance is suspected or in high-risk cases. Second-generation cephalosporins, ampicillin, and co-trimoxazole may also be used if susceptibility is documented. In children, the preferred first-line agent is azithromycin. Cefixime or ceftibuten may be used in case of resistant strains. Intravenous antibiotics are indicated with suspected or proven severe shigellosis with signs of bacteremia, potentially including lethargy, fever > 102.2 F, underlying immune deficiency, and in children unable to take oral drugs. [24]

In E. coli O157: H7 infections, complete blood count can show leukocytosis, anemia due to hemolysis, and thrombocytopenia. Metabolic profile is important, especially in dehydration, which can result in electrolyte disturbances and uremia. A stool culture may be positive for E. coli 0157:H7. Culturing the stool with sorbitol MacConkey agar can differentiate non-pathogenic E. coli from the pathogenic E. coli O157:H7 as the O157:H7 strain cannot metabolize sorbitol. PCR for the presence of O157: H7 antigens or toxin genes in the stool may be useful. Treatment of E. coli O157 is based on supportive care and hydration of the patient. Most patients recover within ten days with supportive care. Antibiotic therapy does not improve outcomes and may even worsen prognosis by increasing the chances of developing hemolytic uremic syndrome (HUS). In the setting of HUS, patients may require hemodialysis. [26]

During World War II, the Japanese bioweapon program studies the use of Shigella species. Many prisoners died due to experimental inoculation causing dysentery. [4]

E. coli O157:H7 strain is considered a Category B priority pathogen by the CDC as it is a potential food safety threat. [27]

Vibrio cholerae (cholera) [28]

Toxin-producing strains of Vibrio cholerae cause cholera. V. cholerae is a motile, comma-shaped, gram-negative rod that has a single polar flagellum. Cholera is transmitted through the fecal-oral route by contaminated water or food.

Cholera presents with profuse painless diarrhea, abdominal discomfort, and vomiting but without fever. Severe cases can lead to hypovolemic shock as a result of massive fluid and electrolyte loss. Classical diarrhea consists of watery and foul-smelling mucous, which is described as "rice-water" stools. The rate of fluid loss can be up to 1 liter per hour. In the absence of adequate treatment, mortality rates may be as high as 70%. Cholera sicca is a variant of cholera where the fluid accumulates inside the intestinal lumen, followed by circulatory collapse and resulting death before diarrhea presents. [28]

Laboratory tests usually reveal hypokalemia, hypocalcemia, and metabolic acidosis as a result of massive fluid loss, but hyponatremia may not be evident as salt is lost too. Confirmatory diagnosis of V. cholerae is by the isolation of bacteria in stool cultures, PCR, and other rapid tests. Stool cultures remain the gold standard in the diagnosis of cholera. [28]

Oral rehydration therapy (ORT) remains the mainstay in the treatment of acute cholera. The degree of fluid replacement may be determined by the degree of hypovolemia ascertained by a physical exam. Rehydration must be started as soon as cholera is suspected. In patients with severe hypovolemia, intravenous replacement with the appropriate replacement of electrolytes and glucose is key. Oral rehydration may begin as soon as the patient is able to drink. It is also paramount to assess the ongoing fluid losses and replace them appropriately with periodic reassessment of the volume status. Antibiotics are added as an adjunctive treatment in cholera once the volume deficit is corrected. The recommended agents include tetracyclines, macrolides, and fluoroquinolones, with tetracyclines being the most used agents.

Importance in Bioterrorism [4]

Similar to Shigella , the Japanese bioweapon program during World War II experimented with cholera. Numerous prisoners died due to experimental inoculation using Vibrio cholerae .

Yersinia pestis (plague)

Yersinia pestis is a gram-negative, non-motile bacillus with a bipolar staining pattern with Giemsa, Wright, or Wayson staining. [29] As a result of the lymph nodes' pathophysiologic involvement, more than 80 to 95% of Y. pestis infections usually present with suppurative adenitis, known as the bubonic plague. Other presentations include septicemic plague and pneumonic plague. [30]

The most common presentation is the bubonic plague which has a two to eight-day incubation period. Symptoms include sudden fever, chills, headache, and malaise. A bubo develops within a day or so, starting as intense pain and swelling in the regional lymph node area, commonly inguinal, followed by axillary or cervical nodes' involvement. The masses are usually non-fluctuant with overlying warmth. There may be tachycardia and hypotension, indicating progression to shock. There may also be hepatosplenomegaly. Septicemic plague is similar to bubonic plague in most signs, except that there is no associated bubo. [30]

Pneumonic plague commonly occurs following the hematogenous spread of the organism from the bubo and can present with fever, cough, chest pain, and hemoptysis. It can also occur without buboes. Primary pneumonic plague can occur following inhalational exposure to another patient having a cough. Rarely, patients may present with meningitis and pharyngitis. [30]

Suspected patients should be immediately isolated along with droplet precautions for at least 48 hours following initiation of antibiotic therapy. Laboratory personnel should also be informed to allow for precautions while handling samples. In all presentations, a high degree of clinical suspicion is required. In the setting of clinical suspicions, an aspirate taken from the bubo is stained and cultured to demonstrate the organism. Complete blood counts can show significant leukocytosis as well as thrombocytopenia. Neutrophils may demonstrate Dohle bodies, but this may not be specific. Other tests include PCR, immunofluorescence, and ELISA. In the US, confirmation of the diagnosis is possible by sending samples to the CDC for culturing. [30]

Rapid initiation of antibiotics is necessary for effective treatment due to the rapid progression. Aminoglycosides such as streptomycin or gentamicin are considered first-line treatment for seven to ten days. The alternative agents include tetracycline or doxycycline and tetracycline for 14 days. Co-trimoxazole has decreased efficacy as compared to the first-line antibiotics. Chloramphenicol is preferred in case of meningitis. Levofloxacin is also licensed for use in the plague. As Y. pestis is a potential bioweapon, vaccines exist with unconfirmed efficacy, and potentially better vaccines are under production.

Importance in Bioterrorism [29]

Plague is a category A bioweapon as per the CDC. Epidemiology of plague in the event of a bioterrorist attack would be significantly different from natural infections. It would likely be an aerosol leading to a pneumonic plague outbreak. Patients would initially present with symptoms similar to other severe respiratory infections. The incubation period may range between one to six days, and the mortality rate may be substantially based on the strain used. An outbreak of the plague in areas not previously reported to have enzootic infections coupled with an absence of a large number of dead rats would indicate a deliberate bioterrorist attack.

Rickettsial Infections

The CDC has included four rickettsial organisms, including Coxiella burnetii (Q fever), Rickettsia prowazekii (typhus fever), Rickettsia rickettsii (Rocky Mountain spotted fever), and Chlamydia psittaci (Psittacosis), as potential biological weapons. [31] [32]

Coxiella burnetii is an obligate intracellular, gram-negative, pleomorphic bacteria that causes Q fever. C. burnetii exhibits a form of antigenic shift, namely, phase variation, where it exists as a highly infectious phase I form in animals and as a non-infectious phase II form when it is subcultured. [33]

Rickettsia prowazekii is an obligate intracellular, gram-negative bacteria that causes typhus. [34]

Rickettsia rickettsii is an obligate intracellular, Cocco-bacillary organism that causes Rocky Mountain spotted fever. [35]

Chlamydia psittaci is an obligate intracellular, gram-negative bacteria that can infect both mammals and avians, having multiple genotypes. Birds are the major epidemiological reservoir, while human-to-human transmission is rare. [36]

The severity of Q fever may range from being completely asymptomatic to serious illness. The incubation period ranges between two to six weeks. The usual spectrum involves a febrile illness which is usually associated with a headache. The illness plateaus in two to four days, and the patient returns to normal in five to 14 days. The fever may last longer if untreated. There may be atypical pneumonia characterized by non-productive cough, minimal auscultatory findings, and very non-specific findings on chest radiograph. There may also be hepatitis which may be without clinical manifestations, with hepatomegaly or hepatitis with evidence of granulomas on biopsy, which may present as a fever of unknown origin. There can be cardiac involvement in the form of myocarditis or pericarditis, which is a major cause of death. Dermatological manifestations include a pink macular or papular rash on the trunk, seen in about five to 21% of cases. Neurological involvement involves lymphocytic meningitis, encephalitis/meningoencephalitis, or peripheral neuropathy. [33]

For Rickettsia prowazekii, the incubation period ranges between one to two weeks. Symptoms include high fever (105 to 106 F), severe headache, myalgias, delirium, dry cough, stupor, and an erythematous rash which begins on the trunk and spreads peripherally with sparing of the palms and soles. The disease can progress to hypotension, shock, and death. Recrudescent cases can occur even decades after initial infection, presenting as severe headache, high fever, chills, and cough. [34]

Rocky Mountain spotted fever occurs four to ten days following exposure to the Rickettsia rickettsii . The symptoms classically include a triad of fever, headache, and a maculopapular or petechial rash. The rash begins as a maculopapular rash on the wrists and ankles, which can later progress to petechia. Other symptoms and signs include lymphadenopathy, confusion or neck rigidity, vomiting, myalgia, arthralgia, and cardiac involvement. [35]

Psittacosis has an average incubation period of five to 14 days. Symptoms are mainly respiratory, but the system involvement can vary tremendously. The organism can spread hematogenously to other organ systems after initial respiratory replication. The symptoms initially include fever, chills, headache, and cough. Signs include altered mental status, photophobia, neck stiffness, pharyngitis, and hepatosplenomegaly. Other symptoms and signs vary based on the systems involved in the disease. [36]

C. burnetii can be isolated on cell culture media, but as there is a risk of lab transmission, culture should only be attempted in BSL 3 labs. Serology remains the mainstay in the diagnosis of Q fever, with indirect immunofluorescence being the reference test. Patients with acute Q fever can have normal leukocyte counts, thrombocytopenia, elevated transaminases, the presence of smooth muscle, and anti-phospholipase antibodies. In chronic Q fever, there may be anemia, leukocytosis or leukopenia, thrombocytopenia, elevated transaminases, raised serum creatinine, and the presence of smooth muscle autoantibodies, antinuclear antibodies, and rheumatoid factor. Treatment is most effective when initiated within three days of symptom onset. In acute Q fever, the preferred treatment regimen includes doxycycline 100mg/day for 14 days or fluoroquinolones, minocycline, co-trimoxazole. In chronic Q fever, a regimen of doxycycline plus hydroxychloroquine for at least 18 months is preferred. A vaccine is available which may be useful against a bioterrorist event using C. burnetii as the bioweapon. [33]

Serology is the mainstay in diagnosing Rickettsia prowazekii infections. A four-fold increase between the acute and convalescent titers is considered diagnostic. Indirect fluorescence antibody tests, agglutination tests, and enzyme immunoassays are commonly employed. Patients can have an initial IgM response followed by the production of IgG antibodies. Primary treatment of Rickettsia prowazekii infections includes doxycycline 100 mg twice daily for seven to ten days. The alternative regimen includes chloramphenicol 500 mg four times daily for seven to ten days. [34]

The diagnosis of R. rickettsiae infection depends on IgM and IgG serologic responses in the setting of clinical suspicion. Serology can be negative early in the course of the disease, and repeat tests may be warranted. Rickettsia can be cultured but is difficult and has a high BSL requirement due to exposure risk. PCR is an alternative means of diagnosis. The patient can have thrombocytopenia, hyponatremia, and CSF pleocytosis. Doxycycline is the antibiotic of choice for treatment, including in children. Defervescence usually occurs within three days of starting therapy, and treatment is usually continued for seven to ten days or at least three days following defervescence. Mortality rates may be as high as 20% to 30% without appropriate treatment. Prompt initiation of treatment on the grounds of clinical suspicion is recommended. [35]

In psittacosis, workup may show mild leukopenia during the acute phase of the disease, which can later progress to profound leukopenia. There may be anemia likely secondary to hemolysis. Liver transaminase, as well as gamma-glutamyl transpeptidase, may be variably elevated. There may also be raised inflammatory markers. A chest X-ray is abnormal in about 80% to 90% of patients who require hospitalization. Findings on the X-ray include unilateral or bilateral consolidation, miliary lesions, interstitial infiltrates, or nodular infiltrates. The CDC diagnostic criteria for psittacosis include any one of the following in the setting of clinical suspicion: isolation of C. psittaci from respiratory secretions, a four-fold increase in the serum antibody titers between in samples collected two weeks apart, a single IgM antibody titer of 1:16 or higher. The treatment regimen of choice for psittacosis is doxycycline 100 mg twice daily for 10 to 14 days. Alternative regimens including in pregnancy include macrolides such as azithromycin and erythromycin for seven days. Third-line agents include fluoroquinolones, but these are less effective than first and second-line agents. [36]

C. burnetii is a category B biological weapon as per the CDC. Even though it can be disseminated on a large scale, its relatively low mortality rates make it less dangerous than category A agents. However, it might still be more suitable as a biological weapon due to its widespread availability, environmental stability, and potential for aerosolized use. Aerosolised C. burnetii is extremely infectious, with a single bacterium being enough to produce disease. [31]

Concerning other rickettsial organisms, the CDC classifies Rickettsia prowazekii, Rickettsia rickettsii, and Chlamydia psittaci as category B biological weapon agents as well . The minuscule infectious dose required (less than 10 bacteria) coupled with the ability of the organism to aerosolize efficiently and the resulting poor clinical outcomes in patients make them potential bioterror agents. [32]

VIRAL

Variola Major (Smallpox) [37]

Variola major is a DNA virus that belongs to the orthopoxviridae genus and the Poxviridae family, consisting of other poxviruses such as parapoxvirus, suipoxvirus, capripoxvirus, and molluscipoxvirus. Only variola and molluscum contagiosum are specific human viruses. However, the other orthopoxviruses, including vaccinia, monkeypox, and cowpox, can also cause significant illness in humans, but only variola major has human to human transmission. All orthopoxviruses are large, brick-shaped virions with a complex structure and a diameter of about 200 nm. The viruses replicate in the host cell cytoplasm by utilizing a DNA-dependent RNA polymerase.

Symptoms and Signs [37]

After transmission of variola, primary viral replication (primary viremia) occurs at the infection site. Secondary viremia happens around the eighth day after infection, which presents with sudden onset of a fever. After a 12 to 14 day incubation, there can be high-grade fever, malaise, and a headache. There can be an associated maculopapular rash on the oral mucosa, pharynx, and face, spreading to the trunk and limbs. The typical rash is centrifugal and is most prominently visible on the face, limbs, palms, and soles. Smallpox lesions appear over one to two days. Smallpox is infectious during the initial week of the rash. Patients become non-infectious once the scabs separate.

In addition to the ordinary type, three other distinct forms exist. Hemorrhagic type is associated with skin petechiae and mucosal or conjunctival bleeding. The mortality rates associated with hemorrhagic type are high. The flat-type is associated with toxemia and slow onset of skin lesions. This type also has a high mortality rate. The modified type is seen in previously vaccinated patients where the skin lesions evolve rapidly and are variable. This type has a low mortality rate.

Investigations and Management [37]

Smallpox may be clinically diagnosed, but lab confirmation is important during the initial stages of an outbreak. Pustular fluid or scabs from suspected patients should be collected by recently vaccinated personnel using personal protection equipment. The specimen must be collected in an evacuated tube, sealed with tape, and transported in a second water-tight container. The relevant health department labs must immediately be notified. Specimen examination must be performed only in a BSL-4 facility. Identification of the species-specific DNA sequences is the preferred investigation of choice. Electron microscopy, immunohistochemistry, PCR, and serology are also useful. The definitive diagnosis and species identification are based on viral culture and subsequent characterization by PCR.

Before 1972, routine vaccination against smallpox was common in the United States and Europe. This was stopped following the completed eradication of the disease. Protective immunity from vaccination has never been evaluated satisfactorily. Hence, the present population globally is considered immunologically naive and unprotected against smallpox if the disease is reintroduced. The CDC and the WHO maintain a small stockpile of conventional vaccines. There are recent efforts to produce a newer vaccine based on live cell culture. Since only very few doses of the vaccine exist, an Advisory Committee on Immunization Practices in 2001 recommended that preventive vaccination be started in first-line responders, including emergency and other first-line health care and law enforcement personnel, with a booster dose every 10 years. However, at present, widespread vaccination is administered only in case of an epidemic that can potentially occur due to a lab error or deliberate acts of bioterrorism.

No antiviral drugs have been found to be effective against human smallpox infections. Hence, surveillance and containment, which was the strategy used in smallpox eradication in the past, are the strategies currently in place in the event of an outbreak. Contact tracing involving the identification and surveillance of the patients’ contacts are the cornerstones of these techniques. Administration of vaccines within four days of exposure is considered to be effective in preventing smallpox. Vaccinated contacts do not transmit the disease and do not require isolation. Environmental decontamination after a bioterrorist attack using aerosolized smallpox is paramount to control the spread.

Importance in Bioterrorism [37]

Even though smallpox was eradicated completely in 1980, it is still a potentially dangerous bioweapon. The CDC categorizes it as a category A organism due to its ability to easily transmit from human to human. Smallpox has a high mortality rate with the potential to cause panic and subsequent social disruption in the event of a bioterrorist attack. The release of aerosolized smallpox is a looming threat, with numerous models developed for emergency response.

Viral Hemorrhagic Fevers [38]

Viral hemorrhagic fevers include a group of severe illnesses characterized by bleeding manifestations of varying degrees, caused by four virus families, including Arenaviridae, Bunyaviridae, Filoviridae, and Flaviviridae.

Chapare virus (CHPV), which causes Chapare hemorrhagic fever
Guanarito virus (GTOV), which causes Venezuelan hemorrhagic fever
Junin virus (JUNV) causes Argentine hemorrhagic fever
Lassa virus (LASV), which causes Lassa fever
Lujo virus (LUJV), which causes Lujo hemorrhagic fever
Lymphocytic choriomeningitis virus (LCMV) which causes Lymphocytic choriomeningitis
Machupo virus (MACV) which causes Bolivian hemorrhagic fever
Sabia virus (SABV) causes Brazilian hemorrhagic fever
Crimean-Congo hemorrhagic virus (CCHFV), which causes Crimean-Congo hemorrhagic fever
Dobrava-Belgrade virus (DOBV), which causes hemorrhagic fever with renal syndrome
Hantaan virus (HTNV), which causes hemorrhagic fever with renal syndrome
Puumalavirus (PUUV), which causes hemorrhagic fever with renal syndrome
Rift Valley fever virus (RVFV), which causes Rift Valley fever
Saaremaa virus (SAAV), which causes Hemorrhagic fever with renal syndrome
Seoul virus (SEOV), which causes hemorrhagic fever with renal syndrome
Sin Nombre virus (SNV), which causes Hantavirus pulmonary syndrome
Severe fever and thrombocytopenia syndrome virus (SFTSV), which causes severe fever, and thrombocytopenia syndrome
Tula virus (TULV), which causes hemorrhagic fever with renal syndrome
Bundibugyo ebolavirus (BDBV), which causes Ebola virus disease
Marburg marburgvirus (MARV), which causes Marburg hemorrhagic fever
Sudan ebolavirus (SUDV), which causes Ebola virus disease
Tai Forest ebolavirus (TAFV), which causes Ebola virus disease
Zaire ebolavirus (EBOV), which causes Ebola virus disease
Dengue virus (DENV-1-4), which causes Dengue fever
Kyasanur forest disease virus (KFDV), which causes Kyasanur forest disease
Omsk hemorrhagic fever virus (OHFV), which causes Omsk hemorrhagic fever
Yellow fever virus (YFV), which causes Yellow fever

Arenaviridae is associated with rodent vectors and is sub-divided into two groups: the New World and Old World groups. Infection can occur via direct contact with rodent droppings or urine or via aerosol transmission. There can be human-to-human as well as nosocomial infections with high mortality rates. For instance, the Lassa virus has a case fatality rate as high as 50%.

Bunyaviruses are associated with arthropods and rodents. These viruses can present with mild to moderate illness or severe illness with high mortality. For instance, in Crimean-Congo hemorrhagic fever, human-to-human transmission can occur through exposure to blood and bodily fluids with subsequent high mortality.

Filoviruses can cause Ebola and Marburg hemorrhagic fever and are associated with African bats. Human to human transmission is reported with extremely high case fatality rates. Ebola outbreaks tend to have case fatality rates of more than 80% to 90%. Case fatality rates in Marburg hemorrhagic fever have been reported to be around 82% in a previous outbreak.

Flaviviruses are transmitted by arthropods and include the Dengue virus, which is transmitted by the Aedes aegypti mosquito. Dengue fever has a relatively low mortality rate of around 0.8% to 2.5%, but this can increase in more severe forms of the disease, namely dengue hemorrhagic fever.

Symptoms and Signs [38]

Patients with viral hemorrhagic fevers can present with very non-specific symptoms, including fever, headache, and malaise. Common clinical features across the different viral hemorrhagic fevers include arthralgia, retro-orbital pain, eye redness, vomiting, abdominal pain, and diarrhea. There may also be hemorrhagic manifestations, including bleeding gums, epistaxis, petechiae, and other major bleeding episodes.

The lab tests in viral hemorrhagic fevers should include complete and differential blood counts, blood type and cross, coagulation studies, liver function tests, kidney function tests, chest x-ray, urinalysis, urine culture, and blood cultures to rule out other more common differentials. [38] Leukopenia, thrombocytopenia, and transaminitis are commonly encountered. [39] Serological testing for the specific IgM and IgG is useful, but molecular-based testing, including PCR, is the most sensitive test. Virus isolation by cell culture may also be used in diagnostic testing. [38]

Management of viral hemorrhagic fevers relies on early diagnosis to increase the chances of survival and prevent secondary bacterial infections. For a large number of viral hemorrhagic fevers, patients should be isolated with the treating staff using personal protective equipment except in certain viruses such as Dengue. The cornerstone of currently available treatment options is supportive care. A few examples of specific infections include: the Lassa virus and ribavirin improve treatment outcomes when administered early in the course of the infection. In Crimean-Congo hemorrhagic fever, treatment is supportive care. In Ebola virus disease and Marburg hemorrhagic fever, the treatment again involves supportive care. However, there is currently an approved Ebola vaccine against Ebola Zaire. There are no effective antiviral agents available in dengue fever, and management is based on supportive care. A vaccine is currently available in South America and South-East Asia. [38]

Importance in Bioterrorism [40]

Viral hemorrhagic fevers are considered category A bioweapons by the CDC. These viruses are potential candidates as biological weapons as they are stable when aerosolized, can cause severe disease, and are difficult to treat. The Soviet Union and other countries have performed research regarding their use in warfare in the past.

Viral Encephalitis

A number of viruses that can cause encephalitis are considered potential bioweapons. These include tick-borne encephalitis virus (TBEV), Japanese encephalitis, West Nile virus, and Nipah virus.

The tick-borne encephalitis virus (TBEV) is a spherical and lipid-enveloped RNA virus that belongs to the genus of Flavivirus in the Flaviviridae family. Humans usually contract the disease by the bite of an infected tick. Following the bite, the virus replicates locally. Dendritic skin cells serve as the site for viral replication followed by transport to regional lymph nodes. The virus disseminates into the spleen, liver, and bone marrow from the nodes, where it continues to replicate. Following this, TBEV infects the central nervous system and produces typical clinical manifestations. [41]

Japanese encephalitis is the most common naturally occurring cause of viral encephalitis, and it is caused by a flavivirus and is transmitted by Culex mosquitos.

The West Nile virus is a single-stranded, enveloped RNA virus that belongs to the Flaviviridae family. In natural infections, Culex mosquitos are the most common vector. [42]

Nipah virus is an RNA virus that belongs to the Paramyxoviridae family and Henipavirus genus. Nipah virus is a BSL 4 category pathogen and is featured on the WHO's priority list of organisms that are likely to cause outbreaks. [43]

In TBEV, between 70% to 98% of infections are asymptomatic. The incubation period of TBEV infections ranges from two to 28 days. The illness may take on a monophasic or biphasic clinical picture. Patients with monophasic courses usually have central nervous system involvement in the form of meningitis or meningoencephalitis. A small number of patients present with a febrile illness and headache but do not develop meningitis which is termed the abortive form. The first phase correlates with the viremia and manifests as fever, headache, myalgia, arthralgia, malaise, anorexia, nausea, etc., which lasts for two to seven days, followed by an asymptomatic interval for about one week. The second phase presents as meningitis in approximately 50% of patients, meningoencephalitis in about 40%, and meningoencephalomyelitis in about 10% of cases. [41]

In Japanese encephalitis, the incubation period ranges between four to 15 days. A prodrome of non-specific symptoms, including fever, headache, vomiting, diarrhea, and myalgia, is common. Encephalitis develops following this, presenting as altered mental status, confusion, and overt psychosis. Meningism and seizures may develop. Rarely mutism and flaccid paralysis can occur. In the later course of the illness, patients can develop dystonia and choreo-athetoid movements. [44]

In West Nile virus infections, the incubation period varies from four days to two weeks. Symptoms include fever, myalgia, malaise, headache, vomiting, anorexia, and a maculopapular rash on the trunk. In some cases, there may be encephalitis or meningitis and other neurologic presentations, including seizures, muscle weakness, altered mental status, or flaccid paralysis. West Nile infection can also cause myelitis, resulting in a polio-like presentation. In West Nile infections involving the nervous system, mortality is high. [42] [45]

Nipah virus has an incubation period ranging from four to 21 days. It can cause distinct syndromes in the form of acute encephalitis or respiratory illness, or a combination of both, depending on the strain. The mortality rate, too, varies with the strain but is generally high. Some patients may remain asymptomatic or may have a sub-clinical course. The symptomatic disease begins with prodromal symptoms, including fever, headache, and myalgia. Encephalitis can develop within a week, presenting with altered mental status, hypotonia, areflexia, myoclonus, gaze palsy, weakness, and a myriad of other neurological symptoms and signs. Rapid deterioration into a coma and subsequent mortality are reported in some outbreaks. In about 20% of survivors, the patients may have residual neurological deficits. Nipah virus infections also may relapse or present with late-onset encephalitis. The respiratory presentation can present with cough, breathing difficulties, and atypical pneumonia. [43]

A case of TBEV infection is diagnosed by the following criteria: symptoms or signs of meningitis or meningoencephalitis, an elevated CSF cell count, and microbiologic evidence by the identification of specific IgM and IgG. Other than the specific criteria, ESR and CRP may be normal or elevated. Detection of viral RNA by RT-PCR in blood or CSF is limited to the initial phase of the illness, following which it may become negative. TBEV serum IgM antibodies can remain detectable for many months following acute infection, and TBEV IgG antibodies persist lifelong and prevent symptomatic reinfection. No specific antiviral treatment exists for the treatment of TBEV infections. Supportive care remains the mainstay of treatment. Dexamethasone is found to be useful in the reduction of cerebral edema in acute encephalitis. Two vaccines are approved for use in Europe. [41]

In Japanese encephalitis, workup may show leukocytosis or hyponatremia. MRI or CT can show bilateral thalamic lesions or hemorrhage. ACSF study may show significant opening pressure elevation, increased protein, and normal glucose. Japanese encephalitis virus-specific serum or CSF IgM using ELISA is the most useful test. There are no effective antiviral agents licensed for Japanese encephalitis. The cornerstone of management is supportive care. Anti-convulsants are useful for seizure control. In around 30% to 50% of survivors, there may be residual neurological deficits and psychiatric symptoms post-recovery of the acute illness. An effective vaccine in a short-course regimen is currently available against Japanese encephalitis. The CDC recommends the vaccine in people traveling to endemic areas for a long period and travelers to a place with a known outbreak. [44]

In West Nile virus infections, labs can reveal non-specific leukocytosis and raised inflammatory markers. Hyponatremia is common if the nervous system is involved. The definitive diagnosis depends on detecting West Nile virus serology using ELISA for the IgM in serum or CSF samples. A CSF study is usually typical of a viral meningitis picture with elevated protein, lymphocytes, and normal glucose levels. CT brain may not show any features in acute disease, but MRI may be useful to detect CNS involvement after several weeks. Treatment of West Nile virus infection is supportive care. Mild cases may be managed symptomatically with an excellent prognosis. Cases with CNS involvement will usually require rehabilitation with physical and occupational therapy. Some patients have persistent neurological defects, including cognitive, gross, and fine motor abnormalities, even after recovery from the infection. [42]

In Nipah virus infections, throat swabs, blood, urine, and CSF for PCR are the mainstay of diagnosis in a patient suspected of having the disease. These must be done only in a BSL 4 laboratory. Virus isolation using a Vero cell line followed by definitive identification of the virus using PCR is also useful for diagnosis. Still, it may be of limited utility in an outbreak scenario. Serum or CSF IgM by ELISA is also used for diagnosis but may be useful only relatively late in the course of the disease. The serum neutralization test is considered the gold standard but is time-consuming. The management of Nipah virus infection depends on good supportive care. Ribavirin has been reported to decrease mortality, but reports are conflicting. Neutralizing human monoclonal antibodies is approved in an outbreak setting in India based on reports of efficacy. [43] The virus is highly infectious, with human-to-human transmission occurring through the respiratory route and body fluids, thereby necessitating isolation of the patients and strict contact tracing. [46]

Tickborne encephalitis viruses are category C biological weapons as per the CDC. They are emerging viruses that can potentially be engineered for mass dissemination and have the potential for high morbidity and mortality. [47] Japanese encephalitis and West Nile virus are potentially transmissible by aerosolization, which makes them a potential bioweapon. [45]

Due to its high mortality rates, the respiratory route of human to human transmission, and its potential to be weaponized as an aerosol, the Nipah virus is considered a Category C priority organism by the CDC. Prasad et al. developed a lethal model using the Bangladesh strain of the Nipah virus and infected African green monkeys through aerosol exposure and demonstrated a lethality suggesting that the Nipah virus has a high potential for weaponization. [48]

Fungal Agents

Coccidiodes immitis (coccidioidomycosis) and Histoplasma capsulatum (histoplasmosis)

Coccidioides are dimorphic fungi that can exist as mycelia or as spherules. It is endemic in certain states in the United States. In naturally occurring infections, the infectious particles of Coccidioides called arthroconidia are inhaled into the lung by the patient causing coccidioidomycosis or San Joaquin Valley fever. [49]

Histoplasma capsulatum is a soil-dwelling dimorphic fungus present in pockets worldwide and is endemic in certain states of the United States. [50]

In coccidioidomycosis, around 60% of cases are asymptomatic. The incubation period can range between seven to 21 days. The symptoms include fever, cough, breathlessness, and chest pain. Headache, loss of weight, and a rash in the form of a faint maculopapular rash, erythema nodosum, or erythema multiforme may be seen. The combination of fever, erythema nodosum, and arthralgia is called desert rheumatism. Other than the common pulmonary presentation in the form of pneumonia, the patient may present with signs of pulmonary cavities, meningitis, abscesses, or disseminated infection involving multiple systems. [49]

In histoplasmosis, primary infections may be asymptomatic or may present with mild flu-like symptoms. The incubation period ranges between seven to 21 days. Symptoms in acute histoplasmosis include fever, headache, cough, and chest pain. The symptoms usually resolve in 10 days. Arthralgias, erythema nodosum, or erythema multiforme can develop in a small proportion of patients, but this is less common in histoplasmosis than coccidioidomycosis. Some patients may present as chronic pulmonary histoplasmosis in the form of cavitary or non-cavitary illness. In others, there may be disseminated histoplasmosis with uncontrolled growth and proliferation of the fungus in multiple organs, and the patient presents with fever, weight loss, hepatomegaly, and splenomegaly. [50]

In coccidioidomycosis, isolation of coccidioides provides definite evidence of infection, and this can be done through sputum examination in patients suspected to have lung involvement. However, patients may not produce sputum, and fungal cultures may not be feasible or of no growth, and serology may be used to diagnose the disease in these cases. Tube precipitin antibodies may be detected in about 90% of coccidioidomycosis patients in the initial few weeks following exposure. Complement-fixing antibodies can be detected in the body fluids, including in CSF, which helps diagnose coccidial meningitis. An enzyme immunoassay (EIA) based Coccidiosis IgM, and IgG test is available. PCR to detect Coccidioides DNA in clinical specimens are not commercially available but are reported to be 98% sensitive and 100% specific. The treatment of coccidioidomycosis uses fluconazole 400 mg to 1200 mg daily or itraconazole for three months. In fibro-cavitary disease, treatment may be extended to a year. Therapy with azoles is lifelong in case of meningitis. Surgical resection has a role in lung lesions and cavitary lesions amenable to surgery. [49]

In histoplasmosis, workup includes imaging which may reveal healed granulomas in the lungs, liver, or spleen. CBC may reveal bone marrow suppression in the form of a non-specific reduction in any of the cell lines. A bronchoscopic alveolar lavage may sometimes be positive, especially in the setting of cavitary lesions. Complement-fixing antibodies appear three to six weeks after infection in 95% of the patients and can persist for years. A single titer of 1:32 or a fourfold increase is diagnostic of an acute infection. Histoplasmin is the antigen extract of Histoplasma mycelial form. Antibodies to histoplasmin, including C, H, and M, may be detected. ELISA IgM and IgG are also useful in diagnosis. Detection of urinary antigen is useful in acute disease and disseminated histoplasmosis. The urinary antigen levels may be used for diagnosis as well as to assess the response to therapy. Regarding treatment, acute pulmonary infections lasting less than four weeks do not require treatment. In case symptoms persist, itraconazole for three months is the treatment of choice. In chronic disease and non-cavitary disease, therapy is extended to six months, while in cavitary disease, treatment may be required for a year. In disseminated disease, amphotericin-B induction therapy for two to four weeks followed by maintenance therapy with itraconazole for one year is the preferred regimen. [50]

Most of the fungi that are human pathogens tend to produce spores that are naturally designed for airborne spread. There have been reports of the ability of fungal spores that have spread across countries and continents through the airborne route. Specifically, wind storms across California have led to the outbreak of coccidioidomycosis in other non-endemic regions of the United States. The opening of Petri dishes in laboratories has resulted in the dispersal of C. immitis spores and subsequent infections. Lumbering has resulted in histoplasmosis amongst onlookers, which suggests that spore dispersal and subsequent infection can occur. Due to the aerosolization potential and the relatively low inoculum requirement, C. immitis has been included in a select agent list of over 80 organisms with bioweapon potential by the CDC. H. capsulatum exhibits similar properties and hence is an organism of interest in bioterrorism even though not included in this list. [51]

Protozoan Agents

Cryptosporidium parvum (Cryptosporidiosis)

Cryptosporidium belongs to the coccidia protozoan group. More than 15 species of C ryptosporidium are implicated in human infections, with Cryptosporidium hominis and Cryptosporidium parvum being the most commonly encountered organisms. Naturally occurring infections are transmitted through the consumption of contaminated water and the fecal-oral route. [52]

Cryptosporidiosis presents with profuse and watery diarrhea along with features of malabsorption. Symptoms may be cyclical, with alternating periods of worsening and improvement lasting one to two weeks. In a majority of cases, the symptoms resolve without treatment within seven to 14 days. Other than diarrhea, patients may have a fever, nausea, vomiting, and abdominal pain. Immunosuppressed patients may have chronic diarrhea that can last for months to years, or they may also develop complications with other system involvement. [52]

Diagnosis of Cryptosporidium infections relies on identifying Cryptosporidium parasite in stool samples using special stains, antigen detection assays, or PCR tests. Modified acid-fast stains may identify mature oocysts. However, PCR can distinguish the species. Serology is of limited use and may be of value in epidemiological studies. In immunocompetent patients, the treatment of choice is nitazoxanide. Paromomycin or azithromycin are alternatives. In immunocompromised patients, correction of immunodeficiency is paramount in treating the disease, along with addressing the infection. [52]

Cryptosporidium is a category B priority pathogen as per the CDC as it is a potential water safety threat. [37]

Ricin is a highly potent plant toxin derived from the castor bean plant Ricinus communis , grown worldwide for industrial production of castor oil. The plant itself has a storied past with several uses being detailed in various contexts spread throughout history, such as wound healing, as an emetic/purgative, as well as a potential treatment for a host of other medical conditions around the world. Ricin constitutes up to 5% of the press cake's protein content left behind after castor oil extraction. It is toxic by ingestion, inhalation, and injection. Ricin consists of 2 subunits; a catalytic ricin toxin A chain (RTA) and a galactose binding B chain (RTB).

Ricin enters the cell by a multi-step pathway which includes receptor-mediated endocytosis. It is then transported by vesicular transport to the Golgi apparatus and subsequently to the endoplasmic reticulum by a chaperone protein named calreticulin. Ricin is a type two ribosome-inactivating protein. RTA chain inactivates the ribosome by hydrolyzing the N-glycosidic bond of an adenosine residue in the 28 S ribosomal RNA of eukaryotic cells. Ribosome binding is essential for ribosome depurination, inhibition of translation, and subsequent toxicity of RTA in mammalian cells. [53] [54] [55] [56]

Ricin toxicity can occur through ingestion, inhalation, or injection. Most cases of ricin toxicity occur following voluntary or accidental ingestion of castor seeds. The lethal oral dose is estimated to be around one to 20 milligrams per kilogram. About five to six seeds of the castor bean plant are considered lethal in children, while in adults, it about 20 seeds. The clinical presentation usually depends on the route of inhalation. Symptoms usually set in within 12 hours of ingestion and initially may include nausea, vomiting, diarrhea, and abdominal pain. Massive gastrointestinal fluid and electrolyte loss have been described and are complicated by hematemesis and melena and progressing to hepatic failure, renal dysfunction, and death due to multiorgan failure or cardiovascular collapse. Inhalation of aerosol particles between the size of 1 to 5-micrometer diameter can penetrate deep in the lung and cause toxicity. Post inhalation symptoms usually begin immediately or within the first 8 hours and may present as cough, dyspnoea, fever, pneumonia, and pulmonary edema leading to respiratory failure and death. Post injection symptoms may include erythema, induration, the formation of blisters, capillary leak, as well as localized necrosis. [57] [58] [59] [60]

Initial investigations may reveal elevated liver transaminases, amylase, creatinine kinase, electrolyte abnormalities, myoglobinuria, and altered renal function tests. Laboratory detection of the ricin protein depends on immunological assays, liquid chromatography-mass spectrometry, or functional activity assays. Field-based diagnostic tests, including lateral flow assays, provide an effective immunoassay technique for detection. [59] [60]

At present, no antidote or specific therapy exists for ricin poisoning or prevention of the illness after exposure. Hence the treatment is largely supportive and involves airway management and positive pressure ventilation in inhalation toxicity cases. Activated charcoal can be considered in patients who present early without emetic symptoms once the airway is secured. Coagulopathy and dyselectrolytemia should be corrected. Other laboratory parameters such as liver function tests and renal function tests should also be closely monitored. [60] [61] [62]

Ricin is a category B biological weapon as per the CDC. Various studies have been carried out testing the use of ricin as an agent of bioterrorism. In 1978, the Bulgarian dissident Georgi Markov was killed with ricin placed in the tip of an umbrella, which was poked into the back of his leg. In 2003, a package that contained ricin and a letter that threatened the deliberate contamination of water supplies was found in a post office in South Carolina, United States. This became the first potential chemical terrorism event involving ricin in the United States. It is important to develop a multi-disciplinary approach using effective countermeasures with the help of trained healthcare workers and first responders to enable rapid epidemiological and laboratory investigation, disease surveillance, and efficient medical management. [60] [62] [63]

Abrin is a toxic toxalbumin isolated from Abrus precatorius . It is also known as rosary pea or jequirity bean. It can be weaponized for purposes of biowarfare by aerosolization as dry powder/liquid droplets or by adding to food and water as a contaminant. Abrin is a heterodimer consisting of 2 polypeptide chains A and B, linked by a disulfide bond. The mechanism of action is similar to ricin. It enters the cell by endocytosis and inhibits protein synthesis. The A chain acts as an RNA N -glycosidase and cleaves the C-N bond in adenine. The resultant adenine depurination prevents ribosomal binding to elongation factors and thereby prevents protein synthesis. [62] [64]

Abrin is significantly more toxic than ricin. The estimated fatal dose is 0.1 to 1 microgram per kilogram body weight. Poisoning occurs following ingestion of seeds or contamination of food or water. It presents as abdominal pain, vomiting, diarrhea, hemorrhagic gastritis, and renal failure. Following inhalation, pulmonary edema can occur. Cerebral edema, convulsions, and CNS depression can also occur. Death can occur within 72 hours of exposure.

In cases of suspected exposure, monitor laboratory parameters such as CBC, liver transaminases, renal function tests, and electrolytes. Treatment is supportive in the form of fluid resuscitation, ventilatory support, and decontamination measures. No vaccine or antidote has been identified to date. [62] [64]

Abrin is among the strongest plant toxins known and hence can be exploited for use in bioterrorism. Owing to its stability, toxicity, and ease of purification, it has been classified as a category B agent, with potential for use in bioterrorism by the CDC. No cases have been reported so far, but it is important to be vigilant to the possibility of future use. [62] [64]

Botulinum Neurotoxins

Botulinum neurotoxin (BoNT) is among the most toxic substances known to man in its purified form. Its extremely low lethal dose poses a grave biological threat, with high morbidity and mortality. Botulinum neurotoxins are produced by the Gram-positive, spore-forming, anaerobic bacteria of the genus clostridium . The toxin is a double chain protein with a molecular weight of 150 kDa and exists in 7 different serotypes (A - G) with over 40 subtypes. In the past few years, with the help of advanced DNA sequencing techniques, newer serotypes and subtypes have been discovered. In 2013, a new toxin (BoNT/H), produced by clostridium botulinum, was isolated from a case of human infant botulism with lower potency and slower progression of symptoms compared to the other BoNTs.

Several other BoNT like toxins produced by non-clostridial bacterial species such as Enterococcus faecium and Chryseobacterium piperi have also been discovered. BoNTs are zinc endopeptidases and can be produced by several genus clostridium members, most commonly C. botulinum . The active form is made up of a C terminal heavy chain, which has the binding and translocation domains and a catalytic light chain forming the N terminal. A single disulfide bond connects the two chains. The light chain has proteolytic activity and is considered the active part. BoNTs bind selectively and irreversibly to the nerve terminals and cleave SNARE (“Soluble NSF Attachment Protein Receptor”) proteins such as VAMP/Synaptobrevin, Syntaxin, and SNAP-25. The SNARE proteins are responsible for the synaptic vesicle's fusion containing the neurotransmitter acutely choline with the presynaptic plasma membrane. This effectively blocks the release of acetylcholine, leading to flaccid paralysis. [62] [65]

In human beings, botulism is usually caused by serotypes A, B, E, and F. There are six recognized forms of botulism: foodborne, infant, intestinal, wound, iatrogenic, and inhalational, characterized by different routes of exposure and incubations periods. The lethal dose for an adult is 0.7 to 0.9 micrograms of inhaled toxin to 70 micrograms of ingested toxin. Food-borne botulism is usually caused by ingestion of home-preserved food and presents typically within the first 4 hours. Infant botulism occurs by the ingestion of spores in infants one to six months in age and has an incubation period ranging from five to 30 days. Intestinal botulism is caused by the ingestion of spores by children over the age of years and adults and has a variable incubation period. Wound botulism is caused by the germination of spores in a wound and has an incubation period of 1 to 2 weeks.

Iatrogenic botulism is caused by the injection of commercial or non-approved preparations of BoNTs. Inhalation of BoNTs leading to botulism can occur. However, it has not been reported in humans. The clinical presentation is usually not dependent on the route of exposure. It usually presents as a descending, symmetric paralysis. Initially, there is diplopia, dysphagia, dysarthria, followed by dyspnoea due to intercostal respiratory muscle and diaphragm paralysis. Death usually occurs due to respiratory failure. [62] [65]

The diagnosis is difficult and depends heavily on the clinical presentation. Laboratory detection of BoNTs from clinical specimens such as vomitus, gastric aspirate, nasal swabs, or stool samples via mouse bioassay is considered the gold standard. ELISA may be performed on samples such as bronchoalveolar lavage in select cases. Treatment is supportive care in the form of assisted ventilation, hydration, and prevention of secondary infections. Administration of the anti-toxin, preferably within the first 24 hours and not later than 72 hours, to neutralize the circulating BoNTs is a critical step in the management. In the EU, a trivalent (A, B, E; equine) antitoxin is used. In the United States in 2013, a human-derived BoNT antitoxin (BIG-IV) was approved by the FDA to treat infant botulism. [62] [65]

Botulinum neurotoxin is the deadliest toxin known to man. It is categorized as a category A biological agent that can be used for bioterrorism. BoNTs are lethal at low doses (LD 50 is lower than any other known substance) and can be deployed through multiple routes, including aerosols or contaminated food and water. It is also colorless and odorless, making it ideal for silent attacks. However, production, purification, storage, and transportation can prove to be challenging. Vigilance and continued research into BoNTS and BoNT like toxins are necessary to understand and prevent public health catastrophe due to the possible use of such agents for bioterrorism activities in the future. [62] [65]

Clostridium Perfringens Toxins

Clostridium perfringens is a Gram-positive, anaerobic, spore-forming rod known to secrete more than 20 virulent toxins associated with disease in both humans and animals. Six toxins, namely the alpha (CPA), beta (CPB), enterotoxin (CPE), necrotic enteritis B like toxin (NetB), epsilon (ETX), and iota (ITX), have the potential for toxicity. The epsilon and iota toxins have been categorized as category B agents that can be used in biowarfare by the CDC. The epsilon toxin is the most potent of all the toxins produced by C. perfringens . It is the third most potent toxin behind C. botulinum and C. tetani neurotoxins. ETX shows relative resistance to the proteases found in the gastrointestinal tract of mammals. It causes pore formation in the cell membranes, resulting in degenerative and necrotic changes culminating in organ failure. ETX can also bind to myelin fibers in the CNS after crossing the blood-brain barrier resulting in central nervous system demyelination. The iota toxin causes cytoskeleton damage via enzymatic action on ADP ribosylation leading to cell death. Another important toxin is enterotoxin (CPE), which disrupts the tight junctions in the gastrointestinal epithelial cells, causing food poisoning and non-foodborne gastrointestinal diarrhea. [62] [66]

A necrotic inflammatory bowel disease called Dambrand or enteritis necroticans was reported in West Germany after the second world war, facilitated by poor post-war sanitary conditions and malnutrition. The disease seemed to disappear a few years after it was first described. In 1966, a new form of enteritis necroticans, also known as Pigbel, an inflammatory gut disease described as spontaneous gangrene of the small intestine, was reported in Papua New Guinea. Presently C. perfringens is associated with acute watery diarrhea contributing to a significant number of food poisoning cases around the world. It presents as intestinal cramps, watery diarrhea without fever or vomiting about eight to 14 hours after consuming contaminated food. It is self-limiting with low mortality and usually settles within 24 hours. C. perfringens is also associated with non-foodborne diarrhea, such as antibiotic-associated and sporadic diarrhea. C. perfringens has also been associated with pre-term infant necrotizing enterocolitis. Perfringolysin O is a pore-forming toxin that has been implicated in gas gangrene by its synergistic effects with CPA. [62] [66] [67]

In suspected cases of C. perfringens , stool culture and ELISA testing for toxin can be considered. In cases of clostridial myonecrosis, laboratory evaluation with routine blood tests including blood culture, CK level, ABG, and lactic acid, as well as imaging of the affected area with an x-ray or CT scan. Treatment is generally supportive with fluid resuscitation. In clostridial sepsis, the patients may present with shock due to intravascular hemolysis, which occurs secondary to toxin-mediated destruction of red cells. Antibiotic therapy is with penicillin G, clindamycin, tetracycline, or metronidazole. Surgical debridement of necrotic tissue reduces mortality. In severe cases of clostridial myonecrosis, hyperbaric oxygen is shown to improve outcomes. [62] [66] [68]

The epsilon and iota toxins of C. perfringens have been categorized as category B agents that can be used in biowarfare by the CDC. The toxin can be used in an aerosolized form that can be used as a bioterrorist weapon or dispersed in food intended for human consumption. A multidisciplinary approach is necessary to control outbreaks and ensure that the necessary public health departments are aware to minimize spread. [62] [66]

Tetrodotoxin

Tetrodotoxin (TTX) is a lethal neurotoxin found in marine animals. It is about 1200 times more toxic than cyanide and has no known antidote. It acts by inhibiting the transport of sodium ions through voltage-gated sodium channels found in the muscles and nerves, halting the propagation of action potentials and leading to paralysis. TTX was first isolated from pufferfish of the family Tetraodontidae. There is, to this date, no clarity about the origin, biosynthesis, or function of TTX. Pufferfish with other marine animals are believed to harbor bacteria, which produces TTX. The incidence of poisoning is rare and is reported mainly from countries such as Japan, Bangladesh, and Taiwan, where pufferfish is regularly consumed. [69] [70] [71]

Signs and Symptoms

The severity of symptoms is dose-dependent. In most cases, symptoms will start to develop between 30 minutes to 6 hours following ingestion. Symptoms may include headache, perioral numbness, loss of coordination, nausea, vomiting, abdominal pain, and in severe cases, hypotension, cardiac arrhythmia, respiratory failure, and death. [69] [72] [73]

Diagnosis is based on identifying the clinical presentation. No specific laboratory tests exist to confirm tetrodotoxin poisoning. Treatment is supportive. Provide ventilatory support and watch out for cardiac arrhythmia. If the patient presents early gastric lavage or activated charcoal can be considered. There is no antidote to date. [69]

The lethal dose of TTX for a human is about 0.5 to two mg when ingested. Due to its potency, it can be weaponized for biological warfare. Hence, it is important that adequate knowledge be imparted to healthcare professionals about the potential consequences of the same to prevent widespread mortality. [74]

Nerve Agents

Nerve agents are a subcategory of organophosphorus compounds. They are among the most toxic substances known. They are used extensively as insecticides and have contributed immensely to modern agricultural practices. The high toxicity profile, ease of synthesis, and widespread availability of these agents have lead to their use in chemical warfare over the years. The nerve agents are classified into 4 types; 1. the G-series, which include tabun (GA), sarin (GB), soman (GD), and cyclosarin (GF) 2) V-series, where V stands for venomous, which include VE, VG, VM, and VX, Chinese VX and Russian VX, 3) GV-series which have combined properties of both series G and V, for example, GV, 2-dimethylaminoethyl-(dimethylamido)-fluorophosphate and 4) Novichok series of compounds, such as Novichok-5, and Novichok-7. The organophosphorus compounds ( OPCs) cross the dermis's epithelial membrane and the respiratory tract with ease. They then undergo biotransformation into their active form. They bind to the acetylcholine esterase and form a complex, which inhibits the hydrolysis of acetylcholine, causing it to accumulate and leads to a cholinergic crisis. The removal of the functional group in nerve agents makes it more deadly, as the bond between the agent and the enzyme becomes permanent. The acetylcholine esterase is thus irreversibly inactivated, which is known as the aging of the enzyme. [75] [76]

The clinical presentation is usually of cholinergic excess. The lungs and eyes absorb nerve agents the fastest. The presentation may include mitosis, bronchorrhoea, chest tightness, loss of bladder control, salivation, vomiting, sweating, abdominal pain, and cramps. In severe cases, they may present with stupor, convulsions, and respiratory compromise. The intermediate syndrome may occur before 24 hours or after 96 hours of exposure and may present as pneumonia, aspiration pneumonitis, and respiratory failure. [75] [76] [77]

Decontamination after donning appropriate personal protective equipment (PPE) is the most important step. Liquid agents may be absorbed through the skin and pose a threat to those around the suspected case, while inhaled nerve agents are systemically absorbed and metabolized. The first step is to disrobe the patient, rinse with soapy water, remove all jewelry and personal items and shift to the ICU if ventilatory support is required. Treatment includes 3 types of therapies. The first is to administer antimuscarinic agent atropine. The UK military and North Atlantic Treaty Organization (NATO) protocol recommends an initial dose of 5–10 mg intravenous (IV)/intraosseous (IO) atropine for severely poisoned patients, titrated to effect every 5 min until atropinization (reversal of the ‘3Bs’—bradycardia, bronchospasm, bronchorrhea) takes place. If given early, oxides can re-activate the acetylcholine esterase. The most commonly used is Pralidoxime, given as 2g intravenous or intraosseous slow infusion. The third step is appropriate supportive therapy, including ventilatory support and anticonvulsants. [76] [77]

Nerve agents are amongst the most lethal agents used in chemical warfare. The first known nerve agent, Tabun, was developed by the German chemist Gerhard Schrader in the 1930s during his research into the development of new OP insecticides. Following this, many other nerve agents such as Sarin and Soman were developed for military use. In February 2017, Kim Jong Nam, the half-brother of Korean dictator, Kim Jong-un, was assassinated inside the Kuala Lumpur airport. An autopsy identified the nerve agent ethyl N-2-diisopropylaminoethyl methylphosphonothiolate (VX). In 1994, nerve agent sarin was released in the Tokyo subway system, resulting in the poisoning of 640 people. On 4 March 2018, Sergei Skripal, a former Russian military intelligence officer, and his daughter, Yulia Skripal, collapsed on a park bench in Salisbury, the United Kingdom, after eating dinner at a local restaurant. It was later confirmed that Novichok was present in biological sampling from the Skripals as well as from the site of suspected exposure. Chemical warfare with nerve agents poses a considerable threat to the health of the civilian population, military personnel, and peacekeeping forces. Healthcare providers should recognize symptoms of exposure, understand regional and international notification procedures for potential attacks, as well as the indications for and available supply of antidotal therapy. [78] [79] [80]

Clinical Significance

The ever-looming threat of a terrorist attack, in particular, a bioterrorist event, necessitates that healthcare professionals must prepare to manage victims of these catastrophic events. A broad understanding of potential biological weapons, including identifying the offending agent and the steps in the management of the patients, is paramount in limiting the morbidity and mortality associated with a bioterrorist attack. The healthcare professional's initial role in the event of a bioterrorist attack is to identify that an attack has taken place. Bioweapons, especially infectious agents, may simulate naturally occurring infections.

The healthcare professional should be able to differentiate between these by a thorough epidemiological analysis of the outbreak. Once this is identified, appropriate disease-specific interventions can be started to reduce the morbidity and mortality associated with the attack. The choice of the bioweapon may depend on the technical and economic capabilities possessed by the terrorist organization. Healthcare professionals should be familiar with both the epidemiology and the control measures in such an event to respond if an outbreak should occur. Research targeted at improving the diagnostic and therapeutic capabilities as well as the implementation of effective response plans is another step against bioterrorism. Training healthcare workers and other frontline workers in identifying and managing a bioterrorist attack with regular refresher sessions may also be useful.

Panic and fear among the public can be another aspect of a bioterrorist attack. Healthcare workers also have a role in minimizing panic by explaining the situation to the victims and starting appropriate and timely management to minimize the agent's impact. With prompt identification of the causative biological weapon along with rapid initiation of treatment and containment measures, healthcare professionals can play a direct role in preventing mass casualties and limiting large-scale damage to human life.

Enhancing Healthcare Team Outcomes

The management of a patient who is a victim of an act of bioterrorism is challenging and complex. This requires an interprofessional team consisting of healthcare professionals that include physicians in different specialties, nurses, laboratory technologists, pharmacists, and possibly governmental agencies. Without rapid identification of the causative agent followed by proper management, morbidity and mortality may be high. It may also lead to an outbreak if an agent with the human-to-human transmission is used. The internist, infectious diseases physician, may rapidly identify the offending pathogen or toxin or medical toxicologist.

The patient will require emergency care and possible intensive care, which requires a team effort. Cross consultation involving the various other medical subspecialties may also be required in the case of the disease's systemic involvement. The need for preparedness by healthcare professionals and an interdisciplinary approach in managing the patient is highly recommended to lower the morbidity and improve outcomes. [Level 5]

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Disclosure: Balram Rathish declares no relevant financial relationships with ineligible companies.

Disclosure: Roshni Pillay declares no relevant financial relationships with ineligible companies.

Disclosure: Arun Wilson declares no relevant financial relationships with ineligible companies.

Disclosure: Vijay Vasudev Pillay declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

Cite this Page Rathish B, Pillay R, Wilson A, et al. Comprehensive Review of Bioterrorism. [Updated 2023 Mar 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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Russia Steps Up a Covert Sabotage Campaign Aimed at Europe

Russian military intelligence, the G.R.U., is behind arson attacks aimed at undermining support for Ukraine’s war effort, security officials say.

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A wide cityscape of Red Square in Moscow.

By Julian E. Barnes

Reporting from Washington

U.S. and allied intelligence officials are tracking an increase in low-level sabotage operations in Europe that they say are part of a Russian campaign to undermine support for Ukraine’s war effort.

The covert operations have mostly been arsons or attempted arsons targeting a wide range of sites, including a warehouse in England, a paint factory in Poland, homes in Latvia and, most oddly, an Ikea store in Lithuania.

But people accused of being Russian operatives have also been arrested on charges of plotting attacks on U.S. military bases.

While the acts might appear random, American and European security officials say they are part of a concerted effort by Russia to slow arms transfers to Kyiv and create the appearance of growing European opposition to support for Ukraine. And the officials say Russia’s military intelligence arm, the G.R.U., is leading the campaign.

The attacks, at least so far, have not interrupted the weapons flow to Ukraine, and indeed many of the targets are not directly related to the war. But some security officials say Russia is trying to sow fear and force European nations to add security throughout the weapons supply chain, adding costs and slowing the pace of transfers.

NATO and European leaders have been warning of the growing threat. Prime Minister Kaja Kallas of Estonia said last week that Russia was conducting a “shadow war” against Europe. Prime Minister Donald Tusk of Poland announced the arrest of 12 people accused of carrying out “beatings, arson and attempted arson” for Russian intelligence.

And Prime Minister Jonas Gahr Store of Norway said Russia posed “a real and serious threat,” after his country warned about possible attacks targeting energy producers and arms factories.

Amid the growing concern about sabotage, NATO ambassadors are set to meet next month with Avril D. Haines, the U.S. director of national intelligence. Ms. Haines will provide an intelligence briefing on Russia’s war in Ukraine, but she will also discuss Moscow’s covert sabotage campaign in Europe.

Security officials would not describe their intelligence linking the sabotage to the G.R.U., but American and British spy services have penetrated the G.R.U. deeply. Before the war in Ukraine, the United States and Britain released declassified pieces of intelligence exposing various G.R.U. plans to create a false pretext for Russia’s invasion.

Despite the risk-taking reputation of the G.R.U., U.S. and European security officials said Russia was treading somewhat carefully with its sabotage. It wants to draw attention to the mysterious fires, but not so much attention that it would be directly blamed.

Andrea Kendall-Taylor, a former U.S. intelligence official, said Russia’s plan might be to weaken European resolve. While that outcome may be doubtful, she said it was important for Europe and the United States to come together to respond to the sabotage campaign.

“Russia’s strategy is one of divide and conquer,” said Ms. Kendall-Taylor, now a senior fellow at the Center for a New American Security. “Right now, it’s not a very costly strategy for Russia because we are all responding separately. That is why it is important that over time, we collectivize the response.”

Hoping to do just that, British and other European diplomats have been pressing countries to call out Russian covert operations more aggressively.

One of the first of the recent sabotage acts attributed to Russia was a March fire at a warehouse in London. Authorities say the warehouse was connected with the effort to supply Ukraine but have provided few details.

Security officials briefed on the incident said G.R.U. operatives used a Russian diplomatic building in Sussex, England, to recruit locals to carry out the arson. Four British men have been charged with arson in the attack, and one of them has been charged with assisting a foreign intelligence service.

In response, Britain expelled a Russian military officer working for intelligence services and closed several Russian diplomatic buildings, including the G.R.U. operations center in Sussex.

The use of local recruits, security officials said, has been a hallmark of the recent sabotage campaign. U.S. and European officials said that is partly to make attacks more difficult to detect, and to make them appear to be the result of domestic opposition to supporting Ukraine.

Sabotage acts by Russia in Europe are not unknown. In 2014, Russian military intelligence blew up an ammunition depot in the Czech Republic, although the country did not publicly blame Russia until seven years later.

European governments expelled Russian spies from their capitals after a former Russian intelligence officer was poisoned in Salisbury, England , in 2018 and again following Moscow’s invasion of Ukraine in 2022. The expulsions dramatically curtailed Russia’s ability to mount attacks, said Max Bergmann, the director of the Europe, Russia and Eurasia Program at the Center for Strategic and International Studies.

“There has been a lot of disruption of Russian intelligence activities in Europe,” Mr. Bergmann said. “That caused a pause, and Russian intelligence was consumed by the war in Ukraine. Now they have their footing back and are probably trying to build back up.”

Since the invasion, Russia has appeared intent on not expanding the war into NATO territory. But Ms. Kendall-Taylor said Russia wanted to undermine the alliance and its support for Ukraine.

In the first part of the war, the Russian military performed poorly, and its intelligence agencies were too distracted to conduct covert operations in the West. But with its recent gains on the battlefield and a rebounding military industry, it has dedicated more resources to covert operations.

“They want to take the war to Europe, but they don’t want a war with NATO,” Ms. Kendall-Taylor said. “So they are doing all these things that are short of conventional attacks.”

Forging a proper response, however, will be difficult. The United States and Europe have already imposed sanctions on Russia and expelled Russian spies.

“We are in a very delicate situation because things are already on edge, the Kremlin is already paranoid,” Mr. Bergmann said. “So Western leaders have to tread very carefully with how they respond.”

Julian E. Barnes covers the U.S. intelligence agencies and international security matters for The Times. He has written about security issues for more than two decades. More about Julian E. Barnes

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COMMENTS

Bioterrorism and the Food Supply
Each of the three papers collected in this chapter address a different aspect of a single, highly publicized scenario for foodborne terrorism: the intentional contamination of the U.S. milk supply with botulinum toxin, as described in a May 2005 New York Times op-ed essay by Lawrence Wein (Wein, 2005). The article sparked an intense debate about the possible security risk it posed, a ...
What Is Food Bioterrorism? Bioterrorism: Threat to the U.S. Food System
What Is Food Bioterrorism? Food bioterrorism is an intentional attack targeted against the food system using a disease-causing biological agent. The U.S. food supply is susceptible to intentional contamination by terrorists, where food could be used as a vehicle for introducing harmful disease pathogens into the United States.
(Pdf) Foodborne Zoonotic Agents and Their Food Bioterrorism Potential
Bioterrorism is defined as intentional. release and dissemination of biolo gical. agents. The gro up of biolo gical agents. includes pathogenic microorganisms (vi-. ruses, bacteria and fungi) or ...
Confronting the threat of bioterrorism: realities, challenges, and
Global terrorism is a rapidly growing threat to world security, and increases the risk of bioterrorism. In this Review, we discuss the potential threat of bioterrorism, agents that could be exploited, and recent developments in technologies and policy for detecting and controlling epidemics that have been initiated intentionally. The local and international response to infectious disease ...
Preventing and mitigating food bioterrorism
The term 'food bioterrorism' is generally defined as 'an act or threat of deliberate contamination of food for human consumption with chemical, biological or radionuclear agents for the purpose of causing injury or death to civilian populations and/or disrupting social, economic or political stability' ( WHO, 2002 ).
Analyzing the Threat, Vulnerability, and Consequences of ...
The Public Health Security and Bioterrorism Preparedness and Response Act of 2002 mandates that the U.S. Secretary of Agriculture "by regulation establish and maintain a list of each biological agent and each toxin that the Secretary determines has the potential to pose a severe ... Food traceability allows tracking food products' movement ...
(PDF) Safe Food: Bacteria, biotechnology, and bioterrorism
Food safety and security became the forefront of topics after the 2001 World Trade Center tragedy [34], especially concerns over possible bioterrorism through foods and water hazard begun.This ...
Food and Nutrition at Risk in America: Food Insecurity, Biotechnology
Food and Nutrition at Risk in America addresses the major food and nutrition issues of our time. This groundbreaking and thought-provoking new text offers readers the opportunity to consider the current status of food insecurity, biotechnology, food safety, and bioterrorism in America, as well as the types of assistance and policies needed in the future to ensure the health and welfare of ...
Protecting the Nation's Food Supply from Bioterrorism
Protecting the Nation's Food Supply from Bioterrorism. February 1, 2004. In the aftermath of the terrorist attacks on our country in 2001, and the resulting increased focus on national security, food security has become a top priority for the food industry. Food companies have placed a strong emphasis on reviewing security programs and ...
Threat of a biological terrorist attack on the US food supply: the CDC
Deliberate contamination of food with biological agents has already been perpetrated in the USA. The US food supply is increasingly characterised by centralised production and wide distribution of products. Deliberate contamination of a commercial food product could cause an outbreak of disease, with many illnesses dispersed over wide geographical areas. Dependent on the biological agent and ...
Bioterrorism: Contemporary Issues In Food Safety: Essay Example, 631
Bioterrorism sounds like a terrifying word, doesn't it? It is defined as "an act or threat of deliberate contamination of food for human consumption with chemical, biological or radio-nuclear agents for the purpose of causing injury or death to civilian populations and/or disrupting social, economic or political stability" (JH Bloomberg School of Public Health, 2010).
Biological weapons and bioterrorism: Past, present, and future
Biological warfare has been used for thousands of years. Sometimes known as "germ warfare," biological weapons involve the use of toxins or infectious agents that are biological in origin ...
Agroterrorism: Threats to America's Economy and Food Supply
A subset of bioterrorism, agroterrorism is defined as "the deliberate introduction of an animal or plant disease for the purpose of generating fear, causing economic losses, or undermining social stability." 3 It represents a tactic to attack the economic stability of the United States. Killing livestock and plants or contaminating food can ...
Bioterrorism
Bioterrorism is terrorism involving the intentional release or dissemination of biological agents. [1] These agents include bacteria, viruses, insects, fungi, and/or their toxins, and may be in a naturally occurring or a human-modified form, in much the same way as in biological warfare. [2] [1] Further, modern agribusiness is vulnerable to ...
Food Safety, Food Fraud, and Food Defense: A Fast Evolving Literature
Introduction. Contamination in the context of food can be described as "the introduction or occurrence of an unwanted organism, taint or substance to packaging, food, or the food environment" (BRC 2015).Food safety hazards have been defined as "a biological, chemical, or physical agent in, or condition of, food with the potential to cause an adverse health effect" (CAC 2003; BS EN ISO ...
"Food Deserts" and the Geography of Hunger
Most of us by now have heard and become familiar with the concept of 'food deserts' as geographical areas where food is inaccessible. In her book Black Food Geographies, Dr. Ashanté Reese tackles this terminology in the context of her study of food geographies in the Black neighborhood of Deanwood in Washington, DC.
Food Shortages and Ration Reforms in the Towns and Cities ...
The effects of natural disaster on a society depend, to a great degree, on the state of that society at the time that tragedy strikes.As David Arnold points out, "famine [often] acts as a revealing commentary upon a society's deeper and more enduring difficulties." 1 World War II brought ruin to the Soviet countryside and peasantry. The war's legacy—the dearth of mechanization and ...
The Russian biological weapons program in 2022
The 48th Central Scientific Research Institute employs about 1,400 people, has an annual budget of approximately 1.5 billion rubles (about $25 million), and is headed by Colonel Sergey Borisevich.According to Raymond A. Zilinskas and Philippe Mauger's book "Biosecurity in Putin's Russia, "the 48th CSRI belongs to the Russian Ministry of Defense and is supervised by the Russian General Staff.
What Joan Nathan Taught Me About the Power of Showing Up
Joan is 81, about four years older than my mother. She lost her husband, Allen, just weeks after Orli was diagnosed with liver cancer in late 2019. One afternoon last spring she offered me a spoon ...
Morgan Spurlock, Documentarian Known for 'Super Size Me,' Dies at 53
The film, which debuted at the Sundance Film Festival, grossed over $22 million, made Mr. Spurlock a household name, earned him an Academy Award nomination for best documentary and helped spur a ...
U.S. to Stop Buying Russian Uranium, Cutting Cash to Moscow
A new law accelerates the weaning of U.S. electric utilities from using Russian enriched uranium to power America's nuclear plants. By Max Bearak President Biden signed a bill into law on Monday ...
Comprehensive Review of Bioterrorism
Biological weapons are devices or agents used or intended to be used in a deliberate attempt to disseminate disease-producing organisms or toxins using aerosol, food, water, or insect vectors. Their mechanism of action tends to be broadly through infection or intoxication.[1] Bioterrorism involves the deliberate release of bioweapons to cause death or disease in humans, animals, or plants ...
Under Relentless Russian Assault, Ukraine Adopts a Defensive Crouch
Russia has advanced over about 50 square miles and captured about a dozen villages, many now in rubble. On Friday, President Volodymyr Zelensky of Ukraine said the Russian offensive had reached ...
5 Dead as Iowa Reels From Tornado
May 22, 2024. Southwestern Iowa was reeling Wednesday after a destructive wave of storms, including a tornado, swept across the state the day before, leaving five people dead and at least 35 ...
Putin Is Selling Victory, and Many Russians Are Buying It
But with the war now in its third year, many Russians seem to have learned to accept it, interviews over the last week and recent polling show. And "victory" is an easy sell in Mr. Putin's ...
Opinion
Do Not Allow Putin to Capture Another Pawn in Europe. May 26, 2024, 6:00 a.m. ET. David Mdzinarishvili/EPA, via Shutterstock. Share full article. By Serge Schmemann. Mr. Schmemann is a member of ...
Russia Steps Up a Covert Sabotage Campaign Aimed at Europe
Reporting from Washington. May 26, 2024, 5:03 a.m. ET. U.S. and allied intelligence officials are tracking an increase in low-level sabotage operations in Europe that they say are part of a ...