Many experts in the field of bioterrorism believe it is a matter of when, not if, a country will be subjected to an attack using biological weapons. Why does this threat exist, and why has it suddenly seemed to come to such prominence?

Recent advances in microbiology, together with the increased availability of certain infectious agents, have made production of significant quantities of potential biologic weapons possible. Already, individuals have used biological agents to deliberately induce outbreaks of Shigella dysentriae, Ascaris suum,and Salmonella enteritidis. The S. enteritidis attack in Dallas, Oregon was perpetrated in an attempt to influence a local election. Seven hundred and fifty people became sick after the agent was added to two salad bars.

Is this all just a case of scaremongering, in the same way as we all received advice about how to protect ourselves from nuclear attack in the 60s?

If the threat is real, what can Emergency Departments and Emergency Physicians do to prepare for this? Unfortunately, only time will be able to answer the first question, but reading Cyberounds^® will enable you to answer the second question.

Over the next two sessions of Cyberounds^® Emergency Medicine, we will discuss the issue of biological terrorism. In this session, we will discuss some of the agents that are likely to be encountered in the event of a biological attack. In the next Cyberounds^®, we will look at strategies to help prepare your Emergency Department, your hospital and your community for the possibility of biological attack.

A recent article in the Annals of Emergency Medicine(1) reveals that more than 70% of emergency physicians rate themselves as "less than adequate" or "very poor" in their ability to recognize potential casualties from biological attack. I will use a series of hypothetical scenarios to introduce some questions about a variety of potential biological warfare agents.

Scenario One

You are the emergency physician in a small town in the U.S. Midwest. Your town is near a large military base. You have heard from some of your nurses who live on the base that two days earlier there had apparently been a fire on the base. Your first patient, one morning, is a young man with a fever, chest pain with cough, muscle aches and tiredness. You diagnose a viral syndrome and discharge him with analgesia and advice to rest. Over the next three days, you see a further 15 or so patients who all seem to have the same symptom complex.

Discussions with your colleagues in the emergency department reveal that they, too, have seen a number of patients with similar symptoms. Some have been diagnosed with viral syndromes, while others have received antibiotics for presumed bronchitis or sinusitis.

Things start to go downhill on the fifth day. The young man you saw earlier in the week returns to the department. He arrives via the local ambulance service. He is profoundly hypotensive, with a high fever and delirium. From his mother, we learn that, after being seen, he initially seemed to improve for a day or so, but then became very unwell with high fever and complained of a severe headache.

When you see the patient, he requires extensive resuscitation, including intubation, and intravenous fluids and pressors. A chest x-ray shows mediastinal widening and pleural effusions. After blood cultures and other investigations are completed, the patient receives intravenous antibiotics and is admitted to the intensive care unit.

No sooner have you finished with this disturbing case than another person, who had been seen by one of your colleagues earlier in the week, arrives. Her clinical picture is remarkably similar to that of the first patient and she, too, has similar changes noted on her chest x-ray. By now, you are beginning to suspect that this is some sort of epidemic.

Q. From the information already presented, what biological agent are you suspecting?

A. The picture described is classic for ANTHRAX acquired through an inhalational route. Although many physicians will be familiar with the 'malignant nodule' - a skin manifestation of anthrax acquired through contact with infected animals or animal products - few will have seen a case of inhaled anthrax.

The findings described above are typical -- they are non-specific, followed often by a short period of apparent recovery, or at least improvement, then dramatic and sudden deterioration. The chest x-ray findings -- with mediastinal widening and pleural effusions -- are characteristic. Infiltrates are not seen. In anthrax, the classic picture is one of necrotizing hemorrhagic mediastinitis. Fifty percent of patients may also exhibit hemorrhagic meningitis.

Anthrax may be confirmed through Gram staining of blood or of culture of the bacillus from blood in the later stages of the disease.

Q. What is the mortality from inhalational anthrax?

A. The mortality from inhalational anthrax is close to 100% if not treated within 24 to 36 hours of onset of symptoms. The mortality for 'malignant nodules' (the dermatological manifestation of anthrax) is about 25% if untreated, and less than 1% if treated.

Q. Of course, the next question must be: what is the treatment for anthrax? And how do you treat contacts or potentially exposed persons?

A. Anthrax is treated with intravenous ciprofloxacin, 400 mg every 8 hours, or intravenous doxycycline, 100 mg every 12 hours. Although there have been no reported cases of human-to-human transmission of inhalational anthrax, close contacts, or those also potentially exposed, should receive either of the above antibiotics orally for four weeks, together with three doses, over the four weeks, of the anthrax vaccine. This vaccine is now given routinely to all American military personnel and has been proven in laboratory testing of animals to be very effective in preventing infection, even of highly virulent strains.

Why four weeks? Cases of anthrax have been reported as occurring, suddenly, up to eight weeks after inhalational exposure.

Comment

For those who think this scenario to be farfetched, it has occurred. In Sverdlosk, Russia, in 1979, an accident at a bioweapons production facility resulted in over 60 deaths from inhalational anthrax in civilians living downwind from the facility.

Scenario Two

You work in a large urban emergency department. You receive notification that a terrorist group has announced that they released smallpox organisms into the air at a large sports event held in the city six days earlier. You are asked if you have seen 'Any cases that may potentially be smallpox?'

Q. What does a case of smallpox look like, anyway?

A. A sort of trick question! The answer depends upon what type of smallpox one is talking about.

First, some background. Smallpox is an orthopox virus, a member of the Poxviridae family. It is a large DNA virus. It appears brick shaped under electron microscopy. Smallpox is usually acquired by inhalation of the virus. The same virus may produce two diseases - variola major, a serious illness with a mortality rate greater than 20%, and variola minor, a milder infection with mortality less than 1%. On an individual case basis, it may be difficult to distinguish variola minor from a mild case of variola major.

Variola major itself was divided into five clinical categories:

1. Ordinary type. >70% of cases. Characterized by raised pustular skin lesions. The lesions could be confluent over the face and forearms (associated with >60% mortality), semiconfluent on face, with a discrete rash elsewhere (mortality rate of about 35%), or a discrete rash in all involved areas (mortality less than 10%).
2. Modified type. Seen in vaccinated patients who developed lesions. The lesions were smaller and the course was accelerated.
3. Variola sine eruptione. Patients had a fever but no rash. Laboratory testing was required to make the diagnosis. This type was also seen in patients who were immunized.
4. Flat type. Occurred mostly in children. The pustules remained flat,and were confluent or semi-confluent. It carried a high mortality
5. Hemorrhagic type. Although rare, occurred most commonly in pregnant women, where it carried a very high mortality. There was rapid progression of the disease with prostration, cardiac failure, diffuse bleeding and bone marrow suppression. It was also called 'sledgehammer smallpox.'

Classically, the patient presented with sudden onset of fever, severe headache, backache and malaise. Half of all patients had vomited, while one in ten had diarrhea. Initially, the rash appeared as tiny red spots on the tongue and palate. The rash would then spread from the face to the proximal extremities and trunk, and finally to the distal extremities. The rash progressed, over the course of a week, from papules to vesicles to pustules. The rash was a rich source of the virus, especially from lesions inside the mouth. The rash healed, leaving depigmented, scarred areas. Anywhere from a dozen or so to many thousands of lesions could be present.

As with most viral infections, the mainstay of therapy was good nursing care. Post exposure vaccination was provided and could attenuate the effects of the disease. Mortality was highest at the extremes of age.

Q. Now that you know what you are looking for in a case of smallpox, what would your answer to the question, 'Have you seen any cases yet?,' be?

A. The answer would most probably be 'NO', but should then bemodified by 'not yet'. The incubation period for smallpox is seven to 19 days, with a mean of 12 days. The first two days of symptoms occur prior to the appearance of the rash, and are characterized by fever, headache, backache and malaise. Thus, at six days after the apparent exposure, you would not be surprised to find that there have been no cases as yet.

Q. What would be the pattern of the epidemic if there had been an exposure to smallpox of the crowd at a sporting event?

A. The answer to this does not make pretty reading. From experience of smallpox epidemics in the past, it is estimated that each index case of smallpox would infect ten people. It is unlikely that a definite diagnosis would be reached early enough in an epidemic to prevent this second wave of infection (unless the terrorists announced their act immediately upon its completion). Patients in the second wave would require vaccination within days of their exposure, in order to prevent or attenuate the infection. Failure to capture all patients in the second wave would inevitably result in further waves of infection. In addition, as patients would require isolation therapy in rooms providing negative air pressure and adequate decontamination, the available resources would be rapidly overwhelmed.

It is unlikely that sufficient vaccine could be provided quickly enough to sufficient people to rapidly halt any epidemic. Most of the American population, even those who received smallpox vaccination as children, are probably susceptible to this organism by now (booster shots of smallpox vaccine were required to maintain immunity). Soon, the only practical response would be mass vaccination. Thus, many hundreds of thousands, or even millions, would need to be vaccinated. In 1999, only five to seven million doses of the vaccine were available in the United States. This may sound like a large amount, but it is worth noting that, in 1947, six million New Yorkers were vaccinated in one week in response to a smallpox outbreak which affected eight people. The last naturally occurring case of smallpox was in Somalia in October 1977. In September 1978, two laboratory workers in Birmingham, England contracted the disease after a laboratory accident. There have been no reported cases since.

Q. What makes anthrax and smallpox the most likely agents in a biological weapons attack?

A. Col. Gerald Parker, commander of the US Army Medical Research Institute of Infectious Diseases, has stated: "An effective biological weapon has to be able to be produced in large enough quantities; it has to have the ability to infect large numbers of individuals; it has to remain stable when stored; and it has to retain virulence after aerosol dissemination." This quote was made at a bioterrorism symposium in Arlington VA, February 1999.(2)

NATO has suggested that up to 31 biological agents could have the potential for use as biological weapons. Only a small proportion of these could be easily produced and distributed effectively enough to produce disease. The technology needed to produce some of these organisms is readily available. It is known that the Japanese cult group, Aum Shinrikyo, attempted to use biological weapons it had produced in its own laboratories on a number of occasions between 1990 and 1995 in Tokyo. Fortunately, none of these attacks was successful.

The top four organisms that could be used to wage biological warfare are smallpox, plague, anthrax and botulism. Anthrax and smallpox can be produced reliably, are reasonably easy to aerosolize and are relatively resistant to destruction. This makes them ideal candidates to be used as biological weapons.

Other agents high on the list of possibilities include tularemia, glanders, typhus, Q fever, Venezuelan equine encephalitis, Marburg and influenza viruses.

In our second Cyberounds^® on bioterrorism, we will discuss the steps emergency physicians can take to develop plans for dealing with possible biological weapon attacks.