Bioterrorism and Infectious Agents

I read this book over the weekend. I gave it three stars on goodreads but seriously considered giving it four stars.

The book is from 2005, meaning that some parts of it, particularly I assume those related to diagnostics (genotyping etc.), presumably are a bit dated – progress in vaccine development may also have occurred in the meantime, I wouldn’t know but some authors assumed such a development would be likely in their coverage. Most of the stuff covered is, I think, still as relevant today as it was when it was written.

The book is a Springer publication and contains 10 chapters on various topics related to bioterrorism and specific infectious disease agents which may be used for that purpose. Most chapters deal with specific agents or classes of agents which have the potential to be used in a bioterrorism setting, and only the last two chapters deal with more general topics – the first one of these addresses the bioterrorism setting more generally than do the previous chapters (“When the agent used in a biological attack is known, response to such an attack is considerably simplified. The first eight chapters of this text deal with agent-specific concerns and strategies for dealing with infections due to the intentional release of these agents. A larger problem arises when the identity of an agent is not known. […] in some cases, an attack may be threatened or suspected, but it may remain unclear as to whether such an attack has actually occurred. Moreover, it may be unclear whether casualties are due to a biological agent, a chemical agent, or even a naturally occurring infectious disease process or toxic exposure […] This chapter provides a framework for dealing with outbreaks of unknown origin and etiology. Furthermore, it addresses several related concerns and topics not covered elsewhere in this text.”), whereas the last one very briefly addresses ‘The Economics of Planning and Preparing for Bioterrorism’.

An implicit assumption I’d made before reading this book regarding the bioterrorism setting is that in such a setting we’d know that bioterrorism was taking place – it would be obvious because of all those sick people. But it is far from clear that this would always be the case. Most of the agents have incubation periods measured in days or weeks, and even after symptoms present it may be difficult to realize what’s going on because these diseases are not commonly seen in clinical practise and may be confused with other more common conditions. An aerosolized agent introduced into an environment with a large number of people could infect a lot of people who’d not display symptoms until much later. It’d be difficult to figure out what was going on. A long incubation period incidentally doesn’t necessarily mean the disease isn’t severe; it may well mean that once you get symptoms of a severity that’ll lead you to seek medical attention you’re already screwed. An example:

“Symptoms and physical findings are nonspecific in the beginning of [anthrax] infection. The clinical presentation is usually biphasic. The initial stage begins with the onset of myalgia, malaise, fatigue, nonproductive cough, occasional sensation of retrosternal pressure, and fever. […] anthrax symptoms insidiously mimic flu-like symptoms in the beginning […] In some patients, a brief period of apparent recovery follows. Other patients may progress directly to the second, fulminant stage of illness. The second stage develops suddenly with the onset of acute respiratory distress, hypoxemia, and cyanosis. Death sometimes occurs within hours […] The disease progression from the first manifestation of symptoms until death appears to have a considerable range from a few hours […] to 11 days”

While reading the book, and especially in the beginning, I was a bit surprised more effort was not put into covering the topics briefly addressed in chapter 9 especially (the ‘unknown etiology’ chapter above), but actually the coverage that was chosen matches quite well what they state that they set out to do. The book is written for health professionals: “this volume will provide health care workers with up-to-date important reviews by world-renowned experts on infectious and biological agents that could be used for bioterrorism”. Mostly the book is about the infectious agents and how people affected by these agents may present and what can and should be done in terms of treatment/monitoring/isolation etc., so it makes sense that this work does not include a lot of stuff on what might be termed more general risk management aspects, response modelling, coordination problems and so on; there is a little bit on that stuff in the last chapters, but not much. I’d be very surprised if there are not other books/works published which deal with the risk- and decision-management aspects of this kind of stuff in much more detail (especially given the existence of books like this one).

The fact that the book is written for health professionals (“Emergency physicians, Public Health personnel, Internists, Infectious Disease specialists, Microbiologists, Critical care specialists, and even General practitioners”) means that if you’re not a health professional some of this stuff will be stuff you won’t understand. Patients will not be described as having double vision (they’ll have diplopia), and they won’t be described as ‘sweating a lot’ (they’ll be diaphoretic). The authors assume that when they tell you that the suggested treatment may result in hemolytic anemia you’ll know what that implies, and that you know what G-CSF stands for in the context of adjunctive melioidosis treatment. Usage of abbreviations/acronyms which are not explained is incidentally part of the reason why this book would never get five stars from me; using acronyms without telling you once what the letters stand for is a capital offence in my book. Even if you don’t know much about medicine you’ll learn about exposure routes of various substances/diseases (is person-to-person transmission something I should be worried about? Is it airborne?), symptoms (to some extent – you’ll understand some of the words without looking up the medical terms), prognosis in case of exposure, existence (or lack thereof) of a vaccine/treatment, etc. You’ll also learn a little about the history of some of the substances in question; some of them have been used in warfare before, and extensive research has been conducted on quite a few of them during the Cold War, where both the US and the Soviet Union worked on weaponization of some of these substances.

The 8 chapters on specific biological agents/diseases deal with anthrax, plague, tularemia, melioidosis and glanders, smallpox, hemorrhagic fever viruses, botulism, and ricin. None of these things are nice and you can certainly justify covering them in a book like this. The US Centers for Disease Control and Prevention classifies 6 biological agents as ‘Category A’ biowarfare agents, which is the highest risk category and include agents which “can be easily disseminated or transmitted from person-to-person, can cause high mortality, and have the potential for major public health impact. This category includes agents like smallpox, anthrax, plague, botulinum toxin, and Ebola hemorrhagic fever.” All category A agents are covered in this book, as are a few category B agents. The fact that agents such as ricin (“A dose the size of a few grains of table salt can kill an adult human”) are included in the B category, rather than category A, provides you with a bit of context as to of how awful the agents belonging in the A category are. Many of the agents are not just terrible because they kill a lot of people; some of them will also cause really severe and prolonged morbidity in case people survive. A few examples:

“Patients who require mechanical ventilation, respectively, need average periods of 58 days (type A) and 26 days (type B) for weaning (Hughes et al., 1981). Recovery may not begin for as long as 100 days (Colerbatch et al., 1989).” (Botulism. You may not be able to breathe on your own for a month or two.)

“Smallpox is disfiguring. Older texts suggested removing mirrors from patients’ rooms (Dixon, 1962).”

“Deafness is a very common and often permanent result of LASV [Lassa virus] infection, occurring in approximately 30% of patients (Cummins et al., 1990a).”

“Following parenteral treatment, prolonged oral antibiotics are needed to prevent relapse […] The proportion of patients who relapse can be reduced to less than 10%, and probably less than 5%, if appropriate antibiotics are given for 20 weeks.” (They’re talking about melioidosis victims. You may need to treat these people for months to prevent them from relapsing, and some will relapse even if you do. Melioidosis isn’t unique in this respect: “all persons exposed to a bioterrorist incident involving anthrax should be administered one of these [post-exposure prophylaxis] regimens at the earliest possible opportunity. Adherence to the antibiotic prophylaxis program must be strict, as disease can result at any point within 30–60 days after exposure if antibiotics are stopped.”)

Even the class A agents may be said to some extent to belong on a spectrum. Anthrax doesn’t really transmit from person to person, so the total death toll would mostly be limited to people directly exposed to the agent during an attack (‘mostly’ because e.g. people handling the bodies may be exposed to anthrax spores as well). Pneumonic plague is, well, different. Sometimes the very high virulence of an agent may actually implicitly be an argument against using the agent as a biological weapon in some contexts: “F. tularensis is less desirable than other organisms as a weapon because it does not have a stable spore phase and is difficult to handle without infecting those processing and dispersing the pathogen (Cunha, 2002).”

Especially disconcerting in the context of an attack is the idea of wide-spread panic following release of one of these agents, causing health services to become overextended and unable to help actual victims – they do address this topic in the book:

“An announced or threatened bioterroism attack can provoke fear, uncertainty, and anxiety in the population, resulting in overwhelming numbers of patients seeking medical evaluation for unexplained symptoms, and demanding antidotes for feared exposure. Such a scenario could also follow a covert release when the resulting epidemic is characterized as the consequence of a bioterror attack. Symptoms due to anxiety and autonomic arousal, and side effects of postexposure antibiotic prophylaxis may suggest prodromal disease due to biological agent exposure, and pose challenges in differential diagnosis. This “behavioral contagion” is best prevented by risk communication from health and government authorities that includes a realistic assessment of the risk of exposure, information about the resulting disease, and what to do and whom to contact for suspected exposure. Risk communication must be timely, accurate, consistent, and well coordinated.”

One thing I should perhaps note in this context is that anthrax is not the only one of these agents which ‘for practical purposes’ do not transmit from person-to-person (e.g., “Only two well-documented instances of person-to-person spread are recorded in the [melioidosis] literature”), and that some of those that do actually require quite a bit of exposure to transfer successfully – the ‘everybody who stands next to someone with the Incurable Cough of Death disease and get coughed at will die horribly within 24 hours and we have no cure’-situation will never happen because such diseases don’t exist. On a related note, the faster a disease kills/incapacitates you, the less time the infected individual has to actively transfer it to other people; so even severe and fast-acting diseases will often be self-limiting to some extent. On a related note, “With the exception of smallpox, pneumonic plague, and, to a lesser degree, certain viral hemorrhagic fevers, the agents in the Centers for Disease Control and Prevention’s (CDC’s) categories A and B […] are not contagious via the respiratory route.”

I could cover this book in a lot of detail, but I decided to limit my coverage to talking about the stuff above and then add a few remarks about smallpox and plague here, because I figure these two sort of deserve to be covered when dealing with a book like this.

First, plague. This is not just a disease of the past:

“Improved sanitation, hygiene, and modern disease control methods have, since the early 20th century, steadily diminished the impact of plague on public health, to the point that an average of 2,500 cases is now reported annually […] The plague bacillus is, however, entrenched in rodent populations in scattered foci on all inhabited continents except Australia […] and eliminating these natural transmission cycles is unfeasible. Furthermore, although treatment with antimicrobials has reduced the case fatality ratio of bubonic plague to 10% or less, the fatality ratio for pneumonic plague remains high. A review of 420 reported plague cases in the US in the period 1949–2000 identified a total of 55 cases of plague pneumonia, of which 22 (40.0%) were fatal”

Note that even though the annual number of cases is relatively low, you don’t have to go back to Medieval times to find a rather severe outbreak costing millions of lives:

“The third (Modern) pandemic began in southwestern China in the mid-19th, struck Hong Kong in 1894, and was soon carried by rat-infested steamships to port cities on all inhabited continents, including several in the United States (US) (Link, 1955; Pollitzer, 1954). By 1930, the third pandemic had caused more than 26 million cases and 12 million deaths.”

This is a terrible disease, so of course people have thought about weaponizing it:

“Biological warfare research programs begun by the Soviet Union (USSR) and the US during the Second World War intensified during the Cold War, and in the 1960s both nations had active programs to “weaponize” Y. pestis. In 1970, a World Health Organization (WHO) expert committee on biological warfare warned of the dangers of plague as a weapon, noting that the causative agent was highly infective, that it could be easily grown in large quantities and stored for later use, and that it could be dispersed in a form relatively resistant to desiccation and other adverse environmental conditions […] Models developed by this expert committee predicted that the intentional release of 50 kg of aerosolized Y. pestis over a city of 5 million would, in its primary effects, cause 150,000 cases of pneumonic plague and 36,000 deaths. It was further postulated that, without adequate precautions, an initial outbreak of pneumonic plague involving 50% of a population could result in infection of 90% of the rest of the population in 20–30 days and could cause a case fatality ratio of 60–70%. The work of this committee provided a basis for the 1972 international Biological Weapons and Toxins Convention prohibiting biological weapons development and maintenance, and that went into effect in 1975 […] It is now known that, despite signing this accord, the USSR continued an aggressive clandestine program of research and development that had begun decades earlier, stockpiling battle-ready plague weapons (Alibek, 1999). The Soviets prepared Y. pestis in liquid and dry forms as aerosols to be released by bomblets, and plague was considered by them as one of the most important strategic weapons in their arsenal. […] It is assumed that a terrorist attack would most likely use a Y. pestis aerosol, possibly resulting in large numbers of severe and fatal primary and secondary pneumonic plague cases. Especially given plague’s notoriety, even a limited event would likely cause public panic, create large numbers of the “worried-well,” foster irrational evasive behavior, and quickly place an overwhelming stress on medical and other emergency response elements working to save lives and bring about control of its spread”

“Several simulations of a plague attack have been conducted in the US […] these have involved all levels of government, numerous agencies, and a wide range of first responders […] Two of these […] were based on coordinated national and local responses to simulated plague attacks. During these simulations, critical deficiencies in emergency response became obvious, including the following: problems in leadership, authority, and decision-making; difficulties in prioritization and distribution of scarce resources; failures to share information; and overwhelmed health care facilities and staff. The need to formulate in advance sound principles of disease containment, and the administrative and legal authority to carry them out without creating confusing new government procedures were glaringly obvious […] In the US, several “sniffing devices” to detect aerosolized microbial pathogens have been developed and tested. The Department of Homeland Security and the Environmental Detection Agency have deployed a PCR-based detection system named BioWatch to continuously monitor filtered air in major cities for Y. pestis and other select agents.”

One of the ‘interesting’ aspects is how the effect of such an attack might be magnified by an attack using conventional weapons as well targeting the likely first responders. Imagine the bombing of local hospitals combined with a plague outbreak and widespread panic plus lack of coordination at the higher decision making level – societal collapse combined with pneumonic plague seems like a combination that could really elevate the body count.

…

Okay, lastly: Smallpox. Before going into the details I have express my opinion on this matter: If a person works towards releasing smallpox in order to infect other human beings (and so reintroduce the disease), that person is in my book an enemy of the human race who should be shot on sight. No trial, just kill him (or her).

“Smallpox […] is one of the six pathogens considered a serious threat for biological terrorism […] Smallpox has several attributes that make it a potential threat. It can be grown in large amounts. It spreads via the respiratory route. It has a 30% mortality rate. […] In summary, variola has several virologic attributes that make it attractive as a terrorist weapon. It is easy to grow. It can be lyophilized to protect it from heat. It can be aerosolized. Its genome is large and theoretically amendable to modification.”

“The clinical illness and fatality rate roughly parallel the density of the skin lesions. When lesions are sparse, cases are unlikely to die and probably are not efficient transmitters. However, their mobility may allow them to have enough social interaction to result in transmission […] As lesions become denser and confluent, the fatality rate increases, the amount of virus in the respiratory secretions increases, and patients are more infectious […] Hemorrhagic smallpox has a fatality rate of nearly 100%, and patients are highly infectious. About 1–5% of unvaccinated patients with V. major get hemorrhagic smallpox […] They are usually very sick, usually unable to get out of bed and thus may not transmit efficiently. The clinical presentation (from mild to discrete to confluent to hemorrhagic) is a function of the host response, not the virus. The clinical types do not breed true, in that transmission from any patient can give rise to any of the clinical presentations, and the virus is the same.”

“The individual lesions undergo a slow and predictable evolution. […] By about the 3rd day, the macules become papular, and the papules progress to fluid-filled vesicles by about the 5th day. These vesicles become large, hard, tense pustules by about the seventh or eighth day. […] The pustules are “in” the skin, not just “on” the skin. They are deep-seated […] About the 8th or 9th day, the lesions begin to dry up and umbilicate. By about 2 weeks after the onset of the rash, lesions are scabbing. About 3 weeks after onset, the scabs begin to separate, leaving pitted and depigmented scars. The causes of death from smallpox are not well elucidated. Massive viral toxemia probably causes a sepsis cascade. Cardiovascular shock may be part of the agonal syndrome. In hemorrhagic cases, disseminated intravascular coagulation probably occurs. Antibacterial agents are not helpful. Loss of fluid and proteins from the exudative rash probably contribute to death. Modern medical care might reduce the fatality rate, but there is no way to prove that contention […] There is no proven therapy. No data exist to show whether modern supportive care could reduce the death rate.”

“When smallpox is known to be circulating, the clinical presentation and characteristic rash make diagnosis fairly easy. Diagnosis can be difficult when smallpox is not high on the index of suspicion. Initial cases after a covert bioterrorist attack will probably be missed, at least until the 4th or 5th day of the rash. Transmission may have already taken place by this time. […] Smallpox does not ordinarily spread rapidly. Transmission requires prolonged face-to-face contact, such as that which occurs among family members or caregivers. Transmission is most efficient when the index patient is less than 6 feet from the recipient, so that the large-droplet respiratory secretions can be inhaled […] Since virus is not secreted from the respiratory tract until the end of the prodrome, patients are usually bedridden when they become infectious and usually do not transmit the disease widely. […] No historical evidence exists that smallpox was an effective bioweapon […] what has been written into historical texts and some medical journals may have been fueled more by fear than plausibility.”

“Smallpox virus currently exists legally in only two laboratories: the CDC in Atlanta and at the State Research Center for Virology and Biotechnology in the Novosibirsk region of Russia. Possession of smallpox virus in any place other than these two laboratories is illegal by international convention. A former Deputy Director of the Soviet Union’s bioweapons program has written that, during the cold war, their laboratories produced smallpox in large amounts, and made efforts to adapt it for loading into intercontinental missiles (Alibek, 1999). Scientists defecting from the former Soviet Union, or leaving Russia seeking work in other nations, may have illegally carried stocks of the virus to “rogue” nations (Alibek, 1999; Gellman, 2002; Mangold et al., 1998; Warrick, 2002). There is no publicly accessible proof that such defectors actually transported smallpox out of Russia, but no way of disproving that they did. […] Terrorists with access to a modern virus laboratory might genetically modify smallpox in ways similar to the published manipulations of ectromelia [mousepox] […] Genetically altered strains might pose problems of transmission; alteration of pathogenicity might have unknown effects on the transmissibility of the virus. Experienced intelligence observers feel that terrorists would avoid creating a strain with enhanced virulence. Such strains could devastate developing countries with poor public health systems, and a widespread outbreak would quickly spread to such countries (Johnson et al., 2003). Natural smallpox could similarly boomerang. Terrorists with the ability to manufacture it would realize that an effective attack might cause widespread disease in nations harboring their colleagues. Many such nations have poor public health systems and little vaccine, and would be more devastated than the nation initially attacked”

“The United States stopped routine vaccination in 1972. It could be resumed if the threat of smallpox becomes considerable. Only in a scenario where smallpox becomes widespread would it be wise to resume mass vaccination. […] The current CDC smallpox response strategy is based on pre-exposure vaccination of carefully screened members of first response teams, epidemiologic response teams, and clinical response teams at designated facilities. […] Readiness to control an outbreak resulting from an attack entails a high index of suspicion among clinicians, a good network of diagnostic laboratory capabilities, and a plan for use of surveillance and isolation techniques to quickly contain outbreaks. […] Resumption of widespread vaccination is dangerous and unnecessary.”

Vaccinations are not dangerous because they may cause smallpox to reappear, but rather because there are some other risks involved when getting the vaccination. It’s important to note that Variola major is not the active ingredient in the vaccinations used – rather the vaccinia virus is used, a virus belonging to the same family. There’s more on this stuff here.

As implied by the goodreads rating, I liked this book.