 Well, Denise, we certainly heard some chilling tidbits, I guess, you could say, about the history of plague. Why don't you start us off, now, by talking about the microbiology of this disease? Plague is a disease that results from infection by the bacteria ursinia pestis. The organism is a non-modal gram-negative rod, and when stained, it's easy to see the unique bipolar properties characteristic of this organism, as in the picture here. It's often described as looking like a safety pin. Ursinia pestis organisms have two important properties that differ from bacillus anthracis. First, they are transmissible person-to-person, and second, they do not produce spores. Okay, what does clinical plague look like? There's three clinical manifestations of plague, and with naturally occurring plague, the most common form is bubonic plague. This form is characterized by development of an acute regional lymph adenopathy or swollen lymph nodes near the site of exposure. We call these swollen, painful lymph nodes bubos. Septicemic plague occurs when ursinia pestis invades and continues to multiply in the blood stream. This can occur secondarily to bubonic plague, or can develop without any detectable bubos. Pneumonic plague is actually the least common, but the most dangerous and fatal form of the disease. Okay, let's listen now to an expert on plague, Colonel Russ Byrne, who's chief of bacteriology at USAMR at Fort Detrick, and he's going to describe for us some of the pathogenesis of plague. The pathogenesis of pneumonic plague occurs two ways. The first is, as a complication of bubonic plague, the infection progresses untreated to invade the blood stream followed by seeding of the lungs with progressive pneumonia. The other way ursinia pestis causes pneumonic plague is when it's introduced as an aerosol as a bioagent. In that setting, it's deposited in the alveoli taken up by alveolar macrophages and then transported by lymphatics to local lymph nodes. After this, the change in temperature results in a transformation in the organism. It starts making a lot of the F1 capsule which protects against phagocytosis. In addition, a lot of virulence factors are produced. This accelerates the infection and is probably responsible for the rapid downhill course in untreated pneumonic plague. Death usually occurs within two to five days after the onset of illness. If effective treatment is not initiated within 24 hours, death usually results from pneumonic plague. Okay, Denise, right now we're in the third global pandemic of plague. That would tell me that I should be seeing or I might be expected to see cases of plague. Why are we not seeing more human cases of plague? Actually, plague continues to be an endemic problem in various parts of the world. But we have only a handful of human cases reported each year in the United States, mostly of the bubonic type. You can see here on this graph the number of reported human cases in the U.S. from 1967 to 1997. And of course the reason we still have human plague in the U.S. is because, as we heard earlier, it's a zoonotic disease that's transmitted largely by wild rodents and their fleas to other animals and people. Okay, I think Bill Patrick explained pretty well some of the problems and challenges of weaponizing plague and why it might or might not be a weapon or a viable weapon to certain enemies out there on the battlefield. Again, I want to remind the people out in the audience, plague is transmitted from person to person. And that might make it a less attractive weapon to the battlefield commander. And as I told you earlier, one of the main tenets of most battlefield commanders is maintain control of the battlefield. Plague might be a very awesome and fearsome weapon in one sense, but it is contagious. And furthermore, there's no effective vaccine. So if I use it as a weapon, I subsequently march my troops through, I have to worry that they're going to get plague. And I really have no good way to protect them from getting plague. What's more, as you've already heard, plague is a vector-borne disease. It's transmitted by fleas and those fleas are carried by rats. So when I release my weapon, not only do I infect everybody around me, but I infect all the fleas and rats in the area as well. So I've got to worry about them also. And my problems or the range of infectivity goes well beyond the initial people I intended to affect. So if I'm a battlefield commander, I want to maintain control of the battlefield. Maybe plague isn't that attractive of a weapon. On the other hand, if I'm a terrorist and I want to leverage my gains, then maybe plague looks very attractive indeed. Now let's return to those intrepid doctors on clinical rounds in virtual hospital. And I think you're going to see they probably have another fascinating patient. Today they're fortunate in that Dr. Tom Butler, a world-renowned plague expert from the University of Texas, just happened to be visiting virtual hospital when this particular patient presented to the staff. Hello, P.S.C. Williams. The doctors are here to see you. P.S.C. Williams, I brought a couple other doctors to come see you. I have Dr. Butler, who is one of our outside consultants here visiting. He's an infection disease physician. In addition, I have Lieutenant Colonel C. Slack, who's one of our infectious disease docs. Just want to give you a brief rundown on what's the course of illness. He was on exercise in California for about a week with his unit. Returned yesterday. About midnight last night had the acute onset of rigors, chills, chest pain, and a fever, temp about 102, 103, coughing up some greenish sputum. He's deteriorated throughout the course of the day despite treatment with rithromycin and seftriaxin, and he's developed hemoptysis over the course of the day. Hemoptysis, huh? You know, that, of course, presents an interesting differential, obviously tuberculosis can cause that. Staphylococcal pneumonia comes to mind, pneumococcal pneumonia. Of course, if he was elderly or debilitated, then Klebsiella, really any gram-negative pneumonia, can do this. Are there other members of his unit involved? Well, he was on this exercise with members of his unit. There are about four others who have presented with similar constellation of symptoms at about the same time course. I would like to examine him. Sure, sure. He's by far the worst of the fire. Mr. Williams, does it hurt you when you take a deep breath? Right here. Sharp. Would you breathe? Yes. I hear rails in the chest confirming the presence of pneumonia. Was there a gram stain done on the sputum? Yes, his gram stain showed multiple polys and gram-negative rods. In addition, his CBC showed a white count of about 20,000 with a left shift, and we did blood cultures too, which are pending. With the presence of gram-negative rods in the sputum and several people involved suggests an outbreak, and this could be plague. Plague? Sir, you're thinking it's plague. Will standard respiratory masks be okay? We should wear masks, all of us here in this room, to protect ourselves against droplet spread. Do we need HEPA filter masks or surgical masks already? Surgical masks will be useful. The other important thing to do is get effective antibiotic to treat this possible plague infection. What did you say you had them on? Well, he needs to have either streptomycin, tetracycline, or chloramphenicol. Is there streptomycin available in the formulary? Not streptomycin. No. Well, could we get doxycycline 100 milligrams intravenously as soon as possible? Right now. Can we go ahead and do that now? Sure. Isn't gentamycin another alternative? Yes. Yeah, gentamycin should work as well as streptomycin. We should have that as well. Sir, I'd like to show you the chest x-ray, if I could. Yes, there is an infiltrate in the right lower lobe, and I see some pleural fluid here, suggesting pleural involvement, explaining his right-sided pleuritic chest pain, which is common with plague pneumonia. Dr. Butler, is this a typical clinical presentation that you'd see with pneumonic plague? Yes. When pneumonic plague is primary, that is, a patient inhales an aerosol. In about three days after exposure, patients will develop fever, chills, and cough, shortness of breath. Sometimes the symptoms are nonspecific, including headache, muscle aches. Could this be secondary? Could he have bubonic plague that's generalized to the lungs or spread to the lungs? Yes. Some patients with pneumonic plague will be secondary to a bubo, which is a tender and large lymph node. Do you have any bubo samples? No. Not out of physical. This is probably a primary inhalational plague. There have been two patients in the United States well-described who handled sick cats. The cats had pneumonic plague, and three days after the exposure, they became sick, and both of them died, which was about three days after the onset of symptoms. We can say we're very fortunate that Mr. Williams came to us in less than 24 hours, and we expect you to do well with the antibiotic treatment. However, if treatment is delayed beyond 24 hours, most patients do not have a good outcome. What about other people in his unit who were not ill at this time? Of course, we'll treat the others who are ill similarly as soon as possible. What about the members who were there with him in California but are not ill right now? They should receive prophylactic antibiotic, and the choice is tetracycline or trimethyparamethoxazole. What about the health care providers? People have been taking care of him. They should also receive prophylaxis. Major Nurgis, can we get ahold of his commander and try to get those unit members rounded up? I'll get McCall. I'll bring him into the ER. You can see him there. Well, I really appreciate both of you coming today and sharing your expertise with us. PSC Williams, I think you're going to do okay, right? Hang in there. You've got the medicine going all right. PSC Williams, I'll be back in a few minutes to take care of you. Denise, what did you think? Well, Ted, you and Dr. Butler brought up a really good point in the video. We should emphasize that if you ever encounter a young, otherwise healthy person with bloody sputum and pneumonia who looks like he's deteriorating fast, think of plague. Of course, another clue here was the fact that this man and his unit spent time in California where plague is endemic. That's a good point, Denise. And I really want to emphasize for the people out there in the studio audience that this bloody sputum really is a hallmark of clinical plague. So remember, if you see widened mediastinum on the battlefield, that should make you think anthrax. If you see bloody sputum in an otherwise healthy patient, that should make you think plague. Now, we talked about in the clinical rounds some other things that cause bloody sputum, but most of those like tuberculosis shouldn't cause large numbers of casualties at one time in otherwise healthy patients. So again, bloody sputum in an otherwise healthy patient, think plague. Well, that's what we see in plague as it's progressed quite far along. But how might one suspect plague otherwise? Well, for some insight into that, I think it would be worthwhile to go back to Colonel Byrne and listen to what he has to say. The diagnosis of mnemonic plague in the clinical setting would start with standard tests, the chest X-ray and sputum Gramstein. The chest X-ray is going to show bronchondamonia or low bar consolidation that will progress with progression of the illness. The sputum Gramstein will show polys and it will also be loaded with gram negative bipolar staining bacilli or conchal bacilli. The organism in the Gramstein can be definitively identified as plague by staining with a direct fluorescent antibody that should be available from state public health departments or from the CDC. Later on in the clinical course, the organism can be grown up, identified in the microbiology lab. It's important to remember that plague, your synopestas grows up slowly at 35 to 37 degrees centigrade, which is the standard temperature used in incubators. So if you think you're dealing with a case of mnemonic plague, it's important to continue treatment until you get a definitive answer from the micro lab and this may take two or three days. There are more sophisticated tests for the diagnosis of the presence of plague in serum or in tissues available at you, Samrid, but these are mainly investigational at this time. Okay, so we know what plague looks like and now we know how to diagnose it. Next question is how do we treat it? Well, if you read most civilian textbooks, they'll tell you that Streptomycin is the drug of choice. Now the problem with that is Streptomycin has very few uses in conventional medicine. As an infectious disease doc, I learned about Streptomycin as the fifth line drug of choice for tuberculosis, but aside from that very, very limited usage and so consequently, it's not available in most pharmacies. On the other hand, you can obtain Streptomycin still in 1999 and you would do that by ordering it from the Roryx Streptomycin program at Pfizer Pharmaceuticals. Given that that's pretty difficult, the next question comes to mind is, what about alternative treatment? Denise, maybe you can shed some light on some alternatives to Streptomycin. Sure, Ted. Well, as you discussed in the clinical rounds, the best alternative antibiotics include gentomycin, tetracycline and doxycycline. You shouldn't use beta-lactam as they say because it's been shown that they might actually accelerate mortality. Okay, and the last thing you need to remember out there in the studio audience is that 6% of plague patients will develop a meningitis. And for meningitis secondary to plague infection, you need to use chloramphenicol. It's the only of these drugs that penetrates the blood-brain barrier to a large degree. Now, Dr. Butler, who you saw in our clinical round segment, certainly gained a lot of experience dealing with clinical plague during his years of service with the Army during the Vietnam War. And he's going to relate for us now some of those experiences gained by dealing with clinical plague. Dr. Butler? What made the disease so dramatic is we saw some patients die. And some of them had had symptoms for only two or three days when they died. So it was a very rapidly progressive disease. The other thing that we found that was different from any other bacterial disease I'd ever worked with in the United States was that the bacteremia is such high grade. There's so many bacteria in the blood that you can do a gram stain of a peripheral blood smear and see Bacilli. In fact, one of the first patients I saw at the Vietnamese hospital, we drew some blood and took it back to the Navy laboratory. And we did a blood smear. We were counting platelets as part of a study of disseminated intrapasculator coagulation. And we'd been finding some low platelet counts in patients. In this patient, the technician called me because he said there are very many platelets on this blood smear. I went and looked at the blood smear myself and said these don't quite look like platelets. They're too small. And as I focused down with oil immersion, I saw that these were plague Bacilli. We had obtained the blood and it started treatment. And just as we were about to leave the hospital, we were called back because the nurse said the patient had stopped breathing. Well, we did a resuscitation, mouth to mouth, chest compression. And we worked for about half an hour and gave up. The patient died. And that was the one who had the high grade bacteremia. So that taught me plague is a disease to be respected. It marches through quickly and kills. Now, be mindful that Dr. Butler and the others caring for the patient that you saw, a didn't yet or the patient you heard about, didn't yet have a diagnosis when they were resuscitating that patient. But certainly, if you knew someone had pneumonic plague, you'd want to think twice before performing mouth to mouth resuscitation. Yes. Well, Dr. Butler's discussion brings up the important issue of infection control, which is a major concern with pneumonic plague. Pneumonic plague is a contagious disease and is transmitted by droplets. This means that the particles in the air are fairly large and heavy and tend to fall out of the air quickly, unlike true small particle aerosols that behave like gases. Another example of an infection spread by droplets is meningococcal meningitis. With droplet spread, the contacts at risk are generally only those who have had close face-to-face contact with the ill patient. If someone has maintained a distance of at least six feet from the patient, the risk of contagion is negligible. This is why, when caring for these patients, use of a standard surgical mask is adequate, rather than a HIPAA filter mask, which is required for diseases like smallpox, TB, measles, or varicella. This is, of course, in addition to using standard precautions, which are used when taking care of any patient. A complete list of these precautions is found in Appendix B of the USAMRAD handbook in your student materials. OK, so therefore, droplet precautions should be used when caring for plague patients. Now, for individuals who've had close face-to-face contact with the ill patient, it seems that there are a couple of viable strategies that one could consider. I guess, first of all, you could initiate immediate chemoprophylaxis. And correct me if I'm wrong here. Another option I've heard of is you could closely observe the patient and wait until they develop fever, and then initiate chemoprophylaxis. And probably, at least in the austere environment of the battlefield, I probably wouldn't take chances trying to observe those patients. I would probably start chemoprophylaxis immediately, certainly with pneumonic plague patients. You may choose to watch the context of the bubonic patient. Now, when you talk about chemoprophylaxis, the drug of choice is doxycycline, 100 milligrams, given by mouth twice a day for seven days, or for the duration of contact, whichever is longer. And again, correct me if you disagree with any of that, Denise. Well, in addition, as you sort of pointed out, you need to conduct an epidemiologic investigation to find those individuals who've been exposed and offer chemoprophylaxis depending on the circumstances, or if appropriate, observe them closely for fever and other signs and symptoms of disease. Also, it's important that any patient meeting the case definition of plague be reported through public health channels. Denise, we don't usually think of the word quarantine much anymore, but do you think a public health quarantine would play a role in a widespread outbreak of pneumonic plague? It's a good question, Ted. First of all, patients with pneumonic plague should be isolated for at least 48 hours from the time antibiotics are begun, and continued until there is a favorable response to treatment. Therefore, in a hospital setting, only persons using adequate personal protection, such as surgical masks, would be allowed in the patient's room. If people were being treated at home, you really would want to restrict them to their house and prevent contact with visitors as much as possible. And back to your question, if we had a widespread outbreak of pneumonic plague here in the United States, it is feasible that public health officials in the affected areas would have to establish quarantine procedures to prevent inadvertent spread of the disease while contacts are given prophylactic medications. With the likelihood of extensive air travel by these contacts of patients with pneumonic plague, how are we going to contain an outbreak of plague should one happen? Well, Ted, in 1994 in India, there was an outbreak of a deadly pneumonia that was suspected to be plague. At that time, New York City and New York State Departments of Health worked with the CDC to step up surveillance for plague among passengers arriving on direct flights from India. Persons with suspected plague were evaluated and hospitalized promptly in facilities with respiratory isolation rooms. If this occurred in the US, CDC officials would work closely with local and state public health officials to respond to problems that might cross local, state, or even international boundaries. Unfortunately, the kind of panic that we heard about was probably unnecessary given that there's chemoprophylaxis, at least I assume it would be unnecessary. Now, we have chemoprophylaxis we can use. Once we get a diagnosis, it would seem to me logical that if we start that early enough, the panic could be avoided. But what about immunoprophylaxis? Can we use immunoprophylaxis against plague? Well, the answer is not as simple as it was in the case of anthrax. But let's turn again to Colonel Byrne. And we're going to hear him discuss some of the latest research efforts aimed at developing a new and improved effective vaccine against aerosolized plague exposure. There are two main problems with the plague vaccine. First, the old vaccine did not protect against plague introduced by aerosol challenge. Secondly, the old vaccine is no longer being manufactured because there's not enough of a market in this country. So research efforts were underway in the past to improve the vaccine because of this problem. The best candidate for a replacement plague vaccine is a fusion protein consisting of the F1 capsular antigen and the V antigen. In rodent models of infection, this did protect against plague introduced by aerosol challenge. In small numbers of non-human primates, it also protected against plague introduced by aerosol challenge. The British investigators are also looking at a similar combination. Their product is not a fusion protein, i.e. they're not hooked together biochemically. Their product is simply a mixture of F1 capsular antigen and the V antigen. We're currently planning to study these products in larger numbers of non-human primates that will have more statistical power than the smaller studies done previously. OK, before we move on to smallpox, I have one last interesting tidbit that I'd kind of like to share with you. And this kind of provides me the link between pediatrics and biological warfare defense, my two chosen professions. Now, on your screen in a minute, you'll see, I think, a fascinating picture. Some plague patients developed a rose-colored rash. And this patient probably exhibits that rash better than any I've seen. And the rash forms a ring around her neck. Now, in the poetic language of the Middle Ages, this would have been called a ring around the rosy. Now, of course, in the Middle Ages, we were in the pre-antibiotic era. And I would have very little to offer this girl. So I would stuff her pockets full of posies, both to ward off the stench and in the belief that that might actually have some magical healing powers. But she would die anyway. And because plague was a contagious disease, her body would have been cremated. It would have been turned to ashes. But I have no chemoprophylaxis now to protect myself. So I would have died and my staff would have died as well. We would have all fallen down. So next time your toddler comes home from nursery school singing ring around the rosy, she's being made aware. And her clinical acumen has been increased regarding biological warfare defense. So it's good to know that. Now, we've got a few minutes here to take some time out and answer some of the facts that have been coming in from all around the country. And I'd like to start with this facts. This comes to us from Northampton, Massachusetts, from the Veterans Hospital. And the question is, what are the current bio-warfare capabilities of the US government? And is it true that we have greater bio-warfare capabilities than other countries such as Iraq? Well, interesting question. I like to think that we have better defensive bio-warfare capabilities than Iraq, at least I hope we do. But if you missed it in the history segment, the United States did have an offensive biological program back in the 40s and 50s. And that program started in 1943 in response to a perceived need related to what we thought were very active Japanese and German research programs. We decided we had better get into the biological warfare business as well. We started a program at Camp Dietrich, Maryland, in 43. But in 1969, Richard Nixon unilaterally renounced the use of biological weapons. And he ordered that our offensive stockpile be destroyed. And it was destroyed in 1969. So we don't have an offensive program as of 1969. But again, we like to hope that our defensive capabilities are state of the art. Now, the next question I have, it comes to us from Doctors Hospital in Columbus, Ohio. I'm an Ohio State alumni trained in Columbus, Ohio. And the question is regarding anthrax, would cervical lymph nodes be a characteristic early or late sign of anthrax? And the answer is unfortunately no. It would be nice if we had that useful clinical tip off. But anthrax, again, is a disease of the lymphatics. And when you get inhalational anthrax, what would happen is you would inhale the requisite eight to 10,000 spores. They would get down into your lungs. They would be taken up by pulmonary macrophages, transported to the nearest regional lymph node. And that lymph node would likely be in the medius stynum. So there'd be swollen lymph nodes in the medius stynum, but not likely in the cervical chain. And probably the only exception to that would be cutaneous anthrax of the head and neck. In those cases, maybe you would see increased or enlarged cervical lymph nodes. But very good question. Next question comes to us from Anchorage, Alaska, I believe. And the question is if anthrax was released in the DC Metro Center, as was shown in our fictitious video there, how would the subway system be decontaminated? And how would it be made safe for reuse? Well, that's a great question. And I'm not sure there's a real easy answer to that question. But I'd like to start off trying to answer that by saying that, in general, in the biological warfare and terrorism arena, we put much less emphasis on decontamination than my colleague Lieutenant Colonel Madsen and his folks, the Chemical Defense Institute may have. So in chemical weapons defense, we're very concerned with decontamination. In biological, much less so. And you heard some of the reasons for that. And one of the good reasons is anthrax, again, has a very low secondary aerosolization potential. So if it's blown out there in the initial cloud and you're exposed to it, you're in trouble. But you're not at much risk of that being secondarily aerosolized. But in peacetime, in the continental United States, we're probably not going to take any chances at all. And a good way to decon something like that would be to release parafermaldehyde vapor throughout the subway system. Now, there'd be a lot of logistical questions. How would you seal the subway to do that? But I will leave those answers to the policeman environment. But that would be certainly a good way of doing it. OK, I'm told I have time for one more facts. And this facts comes to us from Fort Sam Houston, Texas, where I was stationed prior to my sojourn here at Fort Detrick. And Fort Sam wants to know, if an immunized person, someone who's fully immunized against anthrax, all six doses of the vaccine receives a very large spore load, then would the immunization protect them? And that's a great question. And we don't have a great answer to that, except to say that you can probably overwhelm virtually any vaccine if the inoculum is high enough. And there have been some theoretical models made. And when you have anthrax released on an unprotected population under ideal meteorologic conditions, you can see 50% casualties as far as 18 kilometers downwind. With proper protection, and that might include anthrax vaccine, the number of casualties would be very minimal. But in all likelihood, it wouldn't be zero. So if you were right near ground zero, weapon went off, you didn't have your mask. Even if you were fully immunized, you got hundreds of thousands of times the otherwise lethal dose 50. In all likelihood, the vaccine would fail. But it would help 99.9% of people who get it, we think. Well, I want to take time now to thank you for all of your questions. We're going to answer more of those later on today if time permits. And hopefully, we'll have plenty of time tomorrow to entertain a lot of questions. Now, I want to move on to viruses, and I want to discuss some of the most serious viral threat agents. And we're going to use smallpox as our representative example of a serious viral threat agent. So let's turn now to smallpox. You are a medic deployed to the Middle East, where tensions are high and rumors abound of possible chemical and biological warfare. Everyone is required to carry mop gear. And you know some units stationed nearby have started taking periodostigmine as a prophylaxis against nerve agent. The hospital you are assigned to has been briefed on the threat. And you have all been vaccinated against anthrax. One evening, you are summoned to evaluate two soldiers who appear to have chickenpox. Oh boy, look at this rash. How long have you noticed this rash for? That's three days. Three days, OK. They're both from a transportation unit stationed about 20 kilometers away. And this looks a little bit like chickenpox. Did you have chickenpox when you were a child? My mom said when I had it when I was 10. OK, any specialists, did you have it when you were a child, chickenpox? Yes. Yeah? OK, and you've been having similar problems? Yes. OK, all right. And you know, did you have your HIV check recently? Yeah, six months. Yeah? OK, good, good. Let's see this here. In addition to the rash, their symptoms include headache, backache, fever, nausea, and fatigue. We just got two patients who came in from about 20 kilometers away with the transportation unit. And they just had this, it's about a day long onset of a rash coming on, a funny rash. They sent them on down here. Chickenpox, maybe? Well, it kind of looks like chickenpox, but it's nothing like I've ever seen before. And both of these soldiers said they've had chickenpox when they were kids. It doesn't look like shingles, not in a dermatomal distribution. You've seen lots of rashes, and you haven't seen anything quite like this. Nothing like I've ever seen. I'm really not sure what it is. OK, again, we're going to use smallpox today as our representative viral agent. Now, just like anthrax and just like plague, smallpox represents another of the great diseases of antiquity. And in fact, it's probably one of the greatest success stories in the history of public health. It is here to fore the only disease to be wiped off the face of the earth. To help us in our discussion of smallpox today, we have back with us Dr. Ali Khan of the CDC and for the first time joining us Dr. D.A. Henderson. Dr. Henderson is the founder of the Civilian Center for Biodefense at Johns Hopkins University. He's also world renowned as the former director of the World Health Organization's smallpox eradication campaign, which went on during the 1960s and 1970s. So very much instrumental in putting the final nail in the coffin of smallpox. Thank you very much for being here today, Dr. Henderson. Can you tell us a little bit about your Civilian Center for Biodefense? Our center at Johns Hopkins is the only university center now dealing with the biodefense. It was created in part to serve as a catalyst to recruit our medical and public health colleagues in dealing with this critical problem posed by bioterrorism. In February, as you know, we had the first national conference for public health and medicine in Washington. And next November, we will have the second ones sponsored by the Department of Health and Human Services and some 12 other professional organizations. We've also convened working groups at the center, which many of those participating here have been part of, in which we've looked at the different agents, identified those a priority, and then looked at what it is we should be doing in terms of response. Reports of these diseases or a working group is appearing in the Journal of the American Medical Association. We've published so far smallpox and anthrax. Others will follow. Dr. Henderson, I was wondering if you could help us understand the disease smallpox. I would venture that no one in our audience, or at least virtually no one, has ever seen a real case of smallpox. The cause of the disease is a smallpox virus. It's a member of the genus orthopox virus and is closely related to viruses causing cowpox, vaccinia, and monkeypox. You can see it has a brick-like appearance on the electron micrograph, perfectly classic. OK. Ollie, let me turn to you. How would someone get infected with smallpox? By what route? Infection with viral virus can occur several different ways. The virus is generally spread by droplet, occasionally by aerosol, and rarely by direct contact with objects. Droplet transmission refers to large respiratory droplets that land on the back of your throat or your nose. Small particle aerosols, especially among patients who have cough or those with hemorrhagic disease, can also spread smallpox generally to a larger number of people than droplets could. Finally, contact spread includes directly touching an infectious patient or indirect contact from objects and other things, such as laundry that are contaminated with infectious virus from a patient. You know, smallpox has some very relevant history with respect to biological weapons development. I think it would be useful to look at Colonel Eitzel now as he reviews the history of smallpox. Before the discovery of the smallpox vaccine, smallpox was, in fact, used as a weapon. One of the best documented examples of this occurred during the French and Indian War. The British had been defeated in their attempt to conquer Fort Carillon on Lake Champlain. So Sir Jeffrey Amherst, commander of the British forces, met with Indians who were sympathetic to the French. Under the pretense of friendship, he deliberately offered them blankets previously used by smallpox victims. The Indians, who lacked immunity to smallpox, suffered a devastating outbreak of the disease. The English were then able to successfully attack the fort, which, by the way, was renamed Fort Taconderoga. Military forces have also been devastated by endemic smallpox. During the siege of Quebec, George Washington's troops suffered massive losses from smallpox. He subsequently required all new recruits to be inoculated against the virus. I'd like to comment for a few minutes on the Soviet program and their development of smallpox, Veral and Major. They first worked with smallpox and immigrated chicken eggs. And since a very small amount of material is produced in the egg, you can imagine the large numbers of eggs that were required to produce 100 metric tons of dried agent. Now, as their program advanced and starting in the early 90s, they were using tissue culture as a means of generating the virus. But 100 metric tons loaded into an ICBM, aimed at our major cities, is cost for worry. It's incredibly ironic that the great public health triumph of eradicating smallpox in the 1970s and the discontinuation of worldwide vaccination have opened the door for this virus to be once again used as a weapon. Dr. Henderson, you have every right to be very proud of facilitating this great triumph of public health, the eradication of smallpox. And we had all but forgotten about smallpox in this country and probably in every other country of the world. Why suddenly is smallpox once again making headlines? Well, Ted, I frankly hoped I'd given my last lecture on smallpox some time ago. There were thousands of people around the world, Globe, who helped eliminate the disease. And indeed saddens me to think that we should have to think about it again. But as Mr. Patrick mentioned, the information we've learned from Soviet defectors about the Soviet biological weapons program has raised everyone's awareness. You know, there are claims that other countries, besides the Soviet Union, such as North Korea, may actually have their hands on the smallpox virus. Now, if that's the case, how would they have gotten it? Well, there are two possibilities. We're not absolutely certain, but it is possible that some countries may have retained some of their smallpox samples and not destroyed them back in the 70s when we asked them to. However, Russia has produced large stocks of smallpox virus and other agents, and many scientists from major bio weapons laboratories have departed for other places. And this raises the all too likely possibility that they may have carried both expertise and material to other laboratories. And the terrorist groups might have rather wide access now to many agents. Well, Dr. Henderson, chances are, if that's true, at least we've been vaccinated. At least if you're as old as I am, you were vaccinated when you were younger. Am I protected against smallpox exposure? The World Health Assembly recommended that all countries cease vaccination against smallpox in 1980. And vaccination of civilians in this country has discontinued in 1972 and military forces in the mid-1980s. So we have a large susceptible population resulting from cessation of vaccination and the weighting of immunity over time. In fact, we would estimate at this time that probably not more than 15 or 20% of the population is immune. So my immunity is waned over time, even though I got vaccinated some time ago in childhood, I probably still don't have immunity that's protective. Very possible you have no immunity at this time. Well, you know, this has broad implications. With a biological terrorist release, an aerosol release could in fact potentially thousands at the very beginning, giving the organism a real jumpstart. It's contagious spreads from there. We know it's stable in aerosol form. We know it's highly effective. And I'm a little concerned about what we're gonna do about this. Ali, I wonder if you could tell us a little bit about the pathogenesis of the disease, how this might play out and help us with that. Sure, Ted. The sequence generally starts with virus landing on the back of a person's throat. And as I said, droplet spread was the most likely transmission. The virus grows and causes a brief, what we generally call a primary viremia that sends additional virus to lymph nodes, spleen, and sometimes a bone marrow. The patient's asymptomatic during this phase. The virus then continues to grow and causes a secondary viremic stage. And that's when you get virus that seeds the back of the throat again and seeds your skin. Now, the prodrome of fever, vomiting, backache, headache, sort of the classic prodrome occurs while the virus is growing in your lymph nodes and spleen. Then the characteristic rash occurs two to three days later after this prodrome and signals that now you too are infectious. The complete sequence from infection to developing the rash is what we generally call the incubation period. And we've talked about this in context of a couple of diseases at this point. Generally, this is 12 to 17 days, with an average of about 12 to 14 days. Okay, so let's go back to those tireless docs then on their rounds at virtual hospital. And they're gonna take a look at their next patient and I'd be surprised to speculate at what they're gonna find. I'll get with physical therapy to see Mr. Davis when we're done here. Great, thanks. All right, tell me about this patient. Sir, this is specialist gross. He's an active duty soldier, is otherwise healthy prior to his admission to the hospital. He was admitted last night as a result of a diminished level of consciousness. The last four or five days he'd been experiencing some very nonspecific symptoms. Fever, headache, vomiting, back pain. His wife had noticed this rash developing two, three days ago. However, we're a little more concerned right now as a result of the fact that he's become more obtunded. So what's going on with anything? Well, we believe varicella, which is why we've put him on a course of acyclovir. Can I tell you something interesting about this guy? Sure. I've been a nearness for a long time. All the varicella patients I've ever seen, their rash always started on their belly and their low back. This guy's rash started on his hands, his feet, and his head, neck, and face. Yes, and you mentioned also that he had some nonspecific symptoms before the rash started. Fever and some backache and things. That, to me, almost sounds like a prodrome and with varicella you don't really get a real remarkable prodrome anyway. So I'm not sure from just hearing that whether this is really varicella, but let's just take a look. I want to look close at the rash here. And I agree with you, Major Nurgis. It looks like he's got what I'd call a centrifugal rash. There's more lesions on the extremities and the face than there are on the trunk. And that is less typical of varicella where in varicella you'd probably see what we call a centripetal rash. There's more lesions on the trunk than the face and extremities. Such that a lot of times mothers don't even notice the child has varicella until they put the child in the bath, they suddenly lift up the shirt and there's a bunch of lesions. The other thing is with varicella you tend to see successive crops of lesions such that you'll see different lesions at different stages of development, like macules, papules, pustules, and then crested lesions. Whereas here, looks to me like he's got, pretty much the lesions are in sync. They're all pustules. I don't see any other types of lesions. So let me just take a little closer. This is unusual too. I see some palmar lesions. Once again, you don't really see those remarkably with chicken pox. In fact, I would say this is a rash that I've never seen before. And I'm kind of concerned also about his mental state. So I'd like to have one of the ID docs take a look at him. I think I saw Dr. Cislak a few minutes ago outside. If you could go get him, I'd like to talk with him. So what have you done so far to work up his mental status change? Well, so we've ordered a CAT scan, but as you know radiology is pretty backed up right now. All right, well, you need to try to impress upon them that this is an urgent need to have this done as soon as possible. In addition, I think, depending on what that shows, you need to do an LP, get some fluid on him. And if we don't find anything from that, let's have neurology take a look at him. All right, so? Dr. Cislak, this young active duty male, otherwise healthy, comes in with this rash and he's pretty uptunded. He's unresponsive chest rub. He's an impressive looking rash. Just wanted to see what you thought. It's not a rash that I've seen before. He's got some palmar lesions and this feels, his pustules are pretty hard to roll through your fingers. You know, obviously the first thing that comes to mind is chicken pox, of course, and this looks a little more impressive than the usual case of chicken pox. Be helpful and know if he's had chicken pox in the past. Yes, sir, he has. Obviously that argues pretty strongly against it. Again, the distribution really doesn't look right either the most of these guys, most of these guys lesions look like they're on the face and that would be fairly atypical for chicken pox. Another thing that comes to mind maybe is measles. This looks more pustular than the typical case of measles. Obviously important bit of history there would be his immunization status. Do you know if he's immune to measles? Sir, we spoke with his wife, but she's not sure. Okay. Rocky Mountain spotted fever is usually a little more particular than this so this doesn't really look like that either but a history of a tick bite or finding a tick on this guy might be helpful. Secondary syphilis can look superficially like this. Maybe Stevens-Johnson really doesn't look real typical for either of those. Maybe an orthopox virus if he had some exotic travel history. I don't know if he were able to get a travel history on him. If he had been to Africa, to Congo, for example, maybe something like monkey pox. I've never seen a case of monkey pox. I'm not sure. I've never seen a case of smallpox either. If this were 30 years ago, I might be tempted to think smallpox. Obviously in 1999 this guy has no reason to have smallpox so I'm not sure. I'm not sure what's going on. I think there are some tests we could do to help us sort things out though. I think it would be useful to get dermatology come down here and grab a piece of this tissue and then you could do a zinc smear and a DFA test on the tissue. That'll at least rule out or rule in the possibility of varicella and if you're gonna have them do that maybe you can actually get somebody to perform electron microscopy on the biopsy material and that should give you a good idea whether this is an orthopox virus or not. I may not tell you exactly which orthopox virus but the information might be helpful nonetheless. I'd probably draw some blood on this guy as well. I think you can get a VDRL titer. I think it would be useful to get measles, IgG and IgM titers, maybe a Rocky Mountain spotted fever titer. I don't think any of those is the answer but I think the information might be helpful nonetheless. So I think I would start there and I think in the meantime I'd just keep this guy in isolation and get masks on everybody and see what the lab results tell us. A surgical mask, okay. I think if you had a HEPA filter mask that'd be ideal if not a surgical mask. You got any of those? We do, sir, they're in the isolation cart. Okay, great. Let's go ahead and get some masks on and thanks for coming by. We'll send you a formal console. Okay, thanks. Well, Dr. Henderson, we saw a patient that looks like they may have smallpox there. I wonder if you could take us through more formally though, the clinical presentation of smallpox. Ted, we have photos of a little girl from Pakistan which illustrates the progression of the smallpox rash. This is a fairly mild form of the smallpox. This is shown here as day three of the rash. The lesions begin as macules, they progress to vesicles, then they form pustules, they ambilicate and finally scabs are formed. Eventually the scabs will fall off between 14 and 28 days after onset of the rash. Similar to chickenpox, the scabs in smallpox are not very infectious because the virus is bound in a fibrin matrix and the patient in the scabbing phase is unlikely to transmit the disease. At this stage in the picture, it's fairly easy to see how the rash could be confused with chickenpox as was noted in the clinical rounds though there are several distinguishing features. Next picture shows the fifth day of her rash and note that the lesions are all in the same stage of development because they progress in synchrony. This is an important distinguishing feature. The rash is more extensive on the face and extremities and includes the palms and the soles whereas the rash in smallpox develops first in the face and just a bit later in the extremities there is no central progression of the rash and limited amount of rash on the chest, on trunk. Chickenpox lesions tend to be more concentrated on the trunk than on the face. They virtually never produce lesions on the palms or soles and you usually see successive crops of vesicles such that you'll see multiple stages at the same time. You'll see scabs and pustules and vesicles together. And finally, we have a picture from the seventh day of rash. You would hope that by this stage it would no longer be confused with chickenpox. Well, Dr. Henderson, I couldn't agree with you more. I think once a case progresses to this point anyone out there should have no trouble diagnosing at least their second case. So the first case might confuse you but once you've seen it once I hope you wouldn't forget it. Remember, not much else looks like this in its full-blown form and that brings us back again to this concept of the clinical hallmarks of disease. Full-blown anthrax produces a medius tonitis, not much else at least on the battlefield that looks like that. Probably not much else in the world of civilian medicine as well. Bloody sputum and an otherwise healthy patient should make you think of plague. This classic centrifugal, synchronous, postular rash should make you think of smallpox and I'm sure you agree with me there. Now, Dr. Henderson, I understand that a colleague of yours, Dr. Don Hopkins at the Carter Center in Atlanta also served with you on the World Health Organization's Eradication Campaign. In fact, I think he was in Sierra Leone if I'm correct and I think it'll be useful to listen to his perspective on the smallpox eradication and on the disease smallpox in general. So let's turn to Dr. Hopkins. It was a really sad thing to see when you knew somebody had smallpox so they were just coming down with it because you and they knew that it was between them and God as to what the outcome would be. People felt very ill. This virus is said to make people feel as though their skin were on fire. Even before the rash begins, they have headache, backache and generally flu-like symptoms felt miserable already, a virile or major. As the virus progresses, people would get these severe rashes on their skin. The same thing often was happening in their throat and in their intestines. And so you have people who are turned into monsters before their eyes, before the eyes of their family and who often die. Some of them who got hemorrhagic smallpox were transformed even more. They were just bleeding from all of their orifices. Most people apparently died just because of overwhelming viremia but also with severe diarrhea, just as their skin could be seeing to descovate. Internally, sometimes people would be losing the entire lining of their bowel or having fluids to ooze into their lungs. Sometimes the virus would attack vital places such as the heart directly, for example. And as infection were on, sometimes people would get secondary infections of the open wounds on their skin but sometimes with very severe rashes, people would just slough great chunks of their skin which would then be open just as if they had been burned to secondary infection. There was also a peculiar stench associated with all of this decaying flesh on a living person. And so to go into a village where you had several people like this and other villagers terrified, some of them unimmunized, was a very sad thing to see. Knowing also that you had nothing to offer a person other than palliative kind of things really when they had progressed to the state of already having the rash. As Dr. Hopkins said, this is a horrible disease, not just from the clinical standpoint but also from a public health standpoint. We know from historical experience that the disease will rapidly spread from person to person in a non-endemic area such as here in our population that doesn't have any residual immunity anymore. Now in endemic areas, it was unusual for a patient to transmit the disease to more than two to five other persons. However, in Europe during the 1960s and 1970s, we did see a number of outbreaks generally due to imported cases in which an infected person transmitted the disease to 10 or 20 additional persons and occasionally more from small particle aerosols. You know, Ollie, I made the point that there's this clinical hallmark that a person who sees a case of smallpox once should never have any trouble diagnosing their second case. But I fear it might not be quite that easy. I fear that not everyone out there is taking our biological defense course and because clinicians out there have not yet seen the disease, it is likely to be misdiagnosed perhaps until the second or maybe even the third generation of cases occurs and by that time I think the horse is out of the barn to some degree. It's gonna be very difficult to implement effective control measures at that point and at least we in the military think that that's one of the reasons, and I'm sure you agree, one of the reasons why smallpox is such a feared biological weapon. I wonder if you had any perspective on that. There are various diagnostics which can be applied in the laboratory. Light microscopy actually is not terribly helpful. Viral cultures are useful, but advancing PCR technology is at this time our best diagnostic tool that is available at both CDC and use AMRAD. Now even though electron microscopy can't distinguish between different poxviruses, any patient in the United States who shows a poxvirus on electron microscopy is almost certainly smallpox because there are no other orthopoxviruses in the United States. So nowadays we would consider smallpox a BSL-4 level agent. I'm gonna do true differentiation, definitive culture gold standard diagnosis by either PCR or viral culture, electron microscopy is presumably gonna be a big tip-off. Presumably not every laboratory or in fact virtually no laboratories is equipped to handle those things safely other than use SAMRAD's laboratory and the CDC's laboratory. So I want to remind the clinicians out there that we are professionals, don't try this at home. If you suspect smallpox you should not be trying to obtain electron microscopy, do PCR, do culture for orthopoxvirus or any of those modalities without talking to Dr. Henderson, Dr. Kahn or somebody at USAMRA at the CDC. I hope you agree, I think you agree. Without a doubt. Dr. Henderson, any other words of wisdom regarding smallpox? Well, I think we need to recall that with smallpox I think this is probably the most serious of the agents simply because it's a capability to spread and spread rather well where anthrax does not. Do we have any treatment for smallpox? Anything licensed during the pipeline? Well, at this point in time we do not. We had no therapy at the time of the eradication program and there's nothing unfortunately at this time now. There's research going on where we can't hold out any hope for the moment. So if I have a smallpox victim and hopefully I never will, hopefully none of us will have another smallpox victim but I guess supportive care is all I can offer by the time they're clinically symptomatic. That's correct. Okay, for you in the audience out there it's important to remember that smallpox like plague is the other biological agent that we typically speak of in a biodefense course that's transmissible from person to person. And obviously as we talked about in the case of plague this has broad implications in the way in which we would manage an intentional release of smallpox or in a terrorism and oral warfare setting. Now, as a pediatrician and I think most of you parents out there know this as well as I do, chickenpox victims, children with chickenpox can go back to daycare when they're scabbed over. But Dr. Kahn, what would the infection control requirements be for smallpox victims? Can they go back to daycare when they're scabbed over? What are we gonna do if we have a large smallpox outbreak, for example? Well, actually Ted, patients are gonna have to be kept in negative isolation when they're sick. Anyone caring for them should ideally be vaccinated and would have to wear HEPA filter masks to sort of fulfill all the requirements for what we say is respiratory isolation. Now for a large outbreak with multiple patients that we probably need to be cohorted together on the same ward as long as the ward had its own ventilation system. Additionally, depending on how many patients there were it could be proposed that patients would either be cared for in their homes or what was done in some countries during their eradication effort. We may actually have to set up smallpox specific hospitals that would have to be opened to take care of these patients. Okay, but so the kid who's scabbed over still can't go back to daycare, still needs to stay in quarantine till all the scabs? Until all the scabs fall off. But as you heard Dr. Henderson say, the virus is in the scabs so that mode of transmission is not very common. It's again the droplet transmission that gets you in trouble and rarely the small particle aerosols that get you in trouble. Okay, well thanks. Well for those of you in the audience again on the last day of the course, the third day we're gonna hear a lot more from the Centers for Disease Control about a smallpox outbreak in Yugoslavia in 1972. And in that outbreak quarantine was a major issue. Now Dr. Kahn, let's move on to another issue central to the discussion of medically managing a smallpox outbreak. The Centers for Disease Control maintain a stockpile of vaccine. Exactly how much vaccine do you have available? Physically we've got 15.4 million doses of vaccine. However, it's really likely that due to normal variations in technique, how you administer the vaccine and wastage that this represents about 78 million effective doses in hand. The vaccine has remained potent after 20 years which is really good but we really can't expect that this is gonna hold true indefinitely. What's the important point here is that we have a certain amount of vaccine that might not all be available in a future outbreak. And the vaccine we will be able to use may actually not be enough depending on the outbreak. However, there is some good news. We may be able to extend this vaccine 10 fold based on some new studies and looking at some old data that suggests diluting the vaccine 10 fold doesn't interfere with this protective ability but will give you the same sort of take. Dr. Henderson, why don't we still make vaccine? Well, the production of the vaccine was discontinued shortly after the disease was eradicated. And since then the production facilities were dismantled and no new vaccine has been produced probably since about 1975. The method of producing vaccine at that time was to shave the flank of calves and to inoculate them with the vaccine virus. After the pustules were formed the lymphatic fluid was scraped off and used for the vaccine after purification. By today's vaccine production standards the vaccinia virus was a very crude preparation indeed. And this procedure would no longer be acceptable for producing new vaccines. So at this time the new vaccines or producing more vaccine will be done on tissue culture in a more modern setting. So there are research efforts underway looking at tissue culture vaccines. There are indeed. And let me pick up on a question we get very often. And that is that the well documented and predictable side effects of this vaccine in addition to death is why the vaccine is not routinely administered at this point. The number of these side effects may be even higher today due to increased people with diseases that impair their immune system. Now because of these issues we stopped routine vaccination in the US actually a decade before smallpox was officially declared eradicated. So it really comes down to a risk versus benefit situation. And fortunately at this point the risk outweighs the benefit for resuming universal vaccination in the United States. Well before we leave the topic of smallpox I'd like to leave the audience with some final food for thought. Now during the last outbreak of smallpox that occurred in New York City in 1948 there were a total of 13 actual smallpox cases but the New York City Department of Health used over six million doses of vaccine to control that outbreak. So one small outbreak could easily wipe out our entire national vaccine stockpile. How much vaccine would we require if we had a large smallpox outbreak from an intentional release next week? And the answer to that question I'm afraid I don't have an answer for. But Dr. Henderson, Dr. Kahn we really appreciate you are being here sharing your experiences and your views with us and your expertise. I wonder if you have any final parting thoughts for the audience? I would just offer one simple parting thought and that is the occurrence of one case of smallpox we regard as an international health emergency requiring that the case be investigated immediately and that health authorities be prepared to move immediately to contain it. I guess that would be the one thing that would get a preventive medicine doc out of bed in the middle of the night. Indeed. I want to pick up on that point. I mean this is where public health really will make the difference. It's not, we need vaccine, we need varicella immunoglobulin, we need needles, but we need early recognition in the community and a robust public health response the moment the first case is recognized in the US or anywhere else in the world. Well thanks. We're gonna move now from the bacteria and viruses to toxins. In this segment of the show we're gonna discuss botulinum toxin because it's the one that's most commonly cited perhaps as a potential weapon for terrorist or for warfare usage. And I'm going to have with me today an expert in toxinology, Dr. David France. Dr. France was the former commander of USAMRAD and he's going to talk to us about botulinum toxin as soon as we watch a video describing botulinum and showing you some of the effects that this could have. Good afternoon. This just in. Hundreds of people attending a week long technology meeting at the downtown convention center are flooding local emergency rooms and doctor's offices with a mysterious illness that public health officials fear could be botulism. 10 people have died from the illness prompting city officials to evacuate the convention center and cordon off the area while special chemical biological teams test for contamination. Botulism, which is not contagious, generally occurs after eating foods contaminated with the botulinum toxin. But so far, health officials have not been able to implicate any common foods eaten by those in the convention center. Because of this, they suspect the illness may have been intentionally transmitted through the air. But at this time, we have no details on who might be responsible. If you or someone you know attended the meeting this week and are experiencing symptoms of general weakness, dizziness, blurred and double vision and difficulties swallowing, report immediately to your local hospital or healthcare facility to be examined. Again, botulism is not contagious and there is no public health risk to those who were not in the convention center area. Stay tuned for further updates on this story. Well, Dr. France, welcome back for your encore presentation. This is the third year in a row you've been with us now and I'd like to start off by asking you, what is a toxin? Thanks, Ted. It's good to be here again. I define a toxin as any toxic substance that can be produced by an animal, plant or a microorganism. Many of these natural toxins, of course, can be produced by chemical synthesis, be man-made or be expressed artificially using genetic engineering. Okay, so what are some of the distinguishing features of toxins and what would differentiate a toxin from a chemical agent, which sounds pretty similar? Good question. From a production standpoint, chemical agents are of course man-made. More important though, functionally, toxins, biological toxins like the other biological agents are neither volatile nor are they dermally active. So usually, toxins don't penetrate the skin. There are some exceptions like the trichothesine mycotoxins, but for the most part they don't. Finally, toxins can be much more toxic than the chemical warfare agents. Botulinum, the one we're going to be discussing, depending on the serotype, can be 10 to 100,000 times more toxic than the chemical agents that we're familiar with. Well, let's move now to some of the specifics about botulinum toxins. Why are we concerned about botulinum toxins as battlefield or terrorist weapons? Well, I think with regard to bot, it's the extreme toxicity that is so well-known, and then the availability that attracts proliferators to this agent, and most of the proliferators in history have attempted to use botulinum toxin, or at least to develop it. The bacteria which produce the toxin are anaerobes. That means they grow in low oxygen environments, and they're called claustridium botulinum. They're ubiquitous in the soil, therefore they're easy to find, they're easy to obtain, and they're relatively easy to grow in the laboratory in fairly simple laboratories, actually. There are seven known serotypes of botulinum toxin, A through Z, all produced by botulinum, claustridium botulinum. A through G. A through G, excuse me. Yes, and they are immunologically distinct. That means that an antibody that protects you against one doesn't protect you against one of the others. The toxins which most commonly affect humans are A, B, and E, and this is not necessarily because the others aren't toxic to humans, it's because humans just don't run across them in their daily lives like they do to those serotypes. Botulinum is clearly a deadly disease. It can affect humans either orally or by inhalation, which is of special concern for warfare or terrorism, or through wound infection. The most common natural intoxication occurs when individuals can foods and can them incorrectly if the foods that are canned contain some of the organisms, the claustridium botulinum, and they're not killed during the canning process. Once they become, this becomes an anaerobic environment, sealed, low oxygen, the toxin can be produced in the can after it's canned. And then if we eat the green beans, a little toxin goes a long way and it can certainly kill us. There's a fourth type and that's called infant botulism. Infants because of the environment in their gut, in their GI tract can actually allow the botulinum bacteria to grow and produce the toxin in the gut and cause intoxication in that way. So if you or I ate spores, it wouldn't affect us, but if an infant ate claustridium botulinum which could potentially get it infected. I think we have a photo of some Iraqi women actually producing vaccines for claustridium showvi, novi and perfringens. These are perfectly legitimate activities in this case. These diseases are, the agents which cause them are also anaerobes, and so they're grown in an anaerobic environment. Those are diseases of livestock. Of livestock. So they're producing legitimate or ostensibly producing legitimate livestock vaccines. Yes, the point I'd like to make is that this kind of a facility could also be used to produce significant quantities of botulinum toxins. Okay, let's take a look now at the history of botulinum toxin from a weapons standpoint. And to do that, I'd like to take you back to Colonel Ed Eitzen. Botulinum toxin is the most lethal substance known to man. So its potential as a weapon was appreciated early on. Supporters of Poncho Villa may have used botulinum against Mexican federalis in 1910. While the details are unclear, it's been said that they left behind recipes where they actually buried pork and green beans for several days. They then dug up this horrible concoction and used it to contaminate food. And they also smeared it on sharp instruments that they used as weapons. During the Second World War, intelligence reports indicated that the Germans were developing botulinum toxin as a cross-English channel weapon to be used against invasion forces. In light of this, it's ironic that a hand grenade filled with botulinum toxins may have been used by Czech patriots who were trained and equipped by the British to assassinate Reinhardt Hydrick, head of the Nazi Gestapo in 1942. In conclusive reports suggest that he died from the effects of the toxin rather than from injuries sustained from the shrapnel. United States interest in botulinum toxins may have grown in part out of our suspicions about the alleged German program. The Soviets studied botulinum as well. While the US actually developed botulinum as one of the lethal agents in its arsenal, both the United States and the Soviets ultimately gave botulinum a lower level of priority because its usefulness for dissemination over large areas was inferior to that of other agents like anthrax and tularemia. Botulinum appears to have been Saddam Hussein's favorite biological weapon. According to United Nations documents, Iraq produced 19,000 liters of liquid botulinum toxins and 8,500 liters of liquid anthrax. Much of this was loaded into bombs and Saddam was apparently fully prepared to use these weapons. Obtaining the bacterial cultures for production of botulinum toxins was unfortunately relatively easy for the Iraqis. The Iraqis got the culture that they used for weaponization from a supply house in the United States and they selected the same culture that we had weaponized back in the 40s and early 50s. So we, by getting this culture from the supply house we saved them a lot of time and energy and effort because they didn't have to go out and search for a very strong toxin producer. Botulinum toxins aren't great open air BW weapons because of their limited range and relative instability but terrorists could potentially use these toxins effectively in enclosed areas or to contaminate food supplies. Colonel France, how do the botulinum toxins do their dirty work exactly? Well, the toxins produced disease in humans are actually in animals for that matter by preventing the release of acetylcholine from the presynaptic nerve terminal. So the nerve transmission can't go to the postsynaptic nerve and then on up. Therefore the nerve impulses are stopped. This results in a flaccid descending paralysis as well as bulbar symptoms as the cranial nerves become involved. The incubation period with botulism can be as brief as 24 to 36 hours from the time of inhalation. So quicker acting weapon than some of the agents we've talked about. Now let's return to our intrepid doctors at virtual hospital and take a look at their next patient. Hi, Mrs. Dobert, we're back again. Mrs. Dobert, how are you doing today? How's she been doing overnight? Any changes? A little, yeah, a change for the worse maybe. Respiratory rates up around 2022. She's still a febrile, but she's complaining about those same symptoms even more. Are you still having the double vision there occasionally and some blurriness? Yeah. How about any trouble swallowing? Has she got real dilated pupils still? Yeah. Let me take a look there. She's real dry because membrane's in there. Mm-hmm. Just gonna take a look inside your mouth, Mrs. Dobert. Just, she sure is flaccid. I think of anything she's worse than yesterday. She looks to kibnit, too. Yeah, she's got diminished gag reflex, too. Would you take your reflexes here? Yeah, those were diminished today, too, compared to yesterday, I think. Yeah, I'm not sure what's going on. I don't know, Guillain-Barre? Yeah, Eaton-Lambare, maybe? I don't have a lot of familiarity with those. I was listening, I was tick paralysis. You guys didn't find a tick on her. Botulism is it? Botulism, I don't know. Have you had any? Do you can your own vegetables at home? No. Do you eat any canned foods that you home canned recently? No. Been in the woods lately where you might have got a tick bite or been traveling anywhere overseas where you might have gotten exposed to something like polio or something like that? No. No. Well, you know, Ted, I'm concerned. She's definitely progressing. She definitely has cranial nerve findings, and she's got this flaccid paralysis. I think it's time we got the neurologists involved. No, I think it's reasonable. You might call a neurologist, I know. You want supplemental O2 while we're at it? Yeah, I think it's reasonable. Yeah, you're probably starting just two liters nasal cannula, and then get it in a pulse ox honor as well. Mrs. Dober, we're going to have Dr. Perkins, one of our neurologists, come up and take a look at you, OK? He'll be up in a little while. Hopefully we'll find out what's going on with you. Don't be scared. We'll just try to do what we can to find out what's going on, all right? You hang in there. Mrs. Dober, I'll be right back. Ted, you know, I had that diagnosis in about 20 seconds, but I spent the rest of the time trying to figure out what was wrong with those two docs and possibly thinking that maybe bot is contagious. Well, I'm not sure what was going on in that scenario. Neurology was never my strong subject, sir. But, you know, in my own defense, 25% of individual cases of botulism or of patients who are the index case in an outbreak of botulism do die. So presumably there are other people out there missing the diagnosis besides myself. I think the take-home message here is that this can be a confusing disease. Physicians could potentially be stumped. And that can be due to the lack of early recognition, to the delayed administration of antitoxin, to the lack of timely ventilatory assistance, all of which would be recommended therapies if required. Now, some patients may just not make it to a care provider in time to do any good. Basically, though, patients should not die of botulism in 1999 because botulism is a survivable disease with first-world medical care. And that's why I think it's important that you out there in the audience understand that this is yet another disease for which there is a clang association, for which there is a clinical hallmark. So we've said that if you see a wide-media stynum and there's no bullet hole in the center of the chest, you should think anthrax. If you see bloody sputum in an otherwise healthy patient with pneumonia, you should think plague. If you see a centrifugal, synchronous, postular rash, you should think smallpox. And if you see a flaxid descending paralysis, especially if you see it in more than one patient, you should think botulism. Again, not much else that causes that symptom complex. So these diseases need not be as difficult as they initially sound. If you just remember those four clinical hallmarks, you should not miss a case of at least these four perhaps most important biological warfare and biological terrorism diseases. So again, flaxid paralysis on the battlefield, especially in an outbreak, should immediately ring the botulism bell in your mind. I hope you agree, Colonel Frantz. I certainly do. Okay. And the key here, Ted, and you hit on it when you were talking about bot, is if you suspect botulinum exposure, it timely treatment with the antitoxin is so critical. It should be done as soon as possible, preferably before the onset of clinical signs, because the antitoxin doesn't work as well after the onset of clinical signs, but it's still indicated. A successful attack with botulinum and aerosol in a city could actually overwhelm the healthcare providing capabilities in that city because anyone who doesn't receive antitoxin in a timely manner is gonna need a ventilator. Well, can you tell us about this antitoxin then? Well, there are several types available. The CDC has a trivalent, A, B, and E, equine IgG product, that's the full IgG molecule. That's a licensed product. Then it used Samurid over the years. We have produced two different products, both equine-dyspeciated products. The FC portion has been removed from the IgG molecule. Right, less immunogenic. That's right, exactly. We have two of those, one a liquid formulation and another one, a more recent one that was developed during and after the Gulf War, which is a lyophilized product. Both of those are IND investigational new drugs and they're both heptavalent, A through G. There is also a small quantity of a human hyperimmune globulin, anti-bot, also heptavalent, which is available. One thing that we need to remember with regard to the equine products is that before they are used, the potential patient or recipient should receive a sensitivity test for the equine product. I understand that human-derived product is, the IND for that is held by the California State Health Department is being used to treat specifically infant botulists. Well, there are two. There's one that's held by the California Health Department and there is also some DoD product as well. Oh, okay, okay. So which one would we use then if we had a large outbreak? I'm starting to get confused by all of these different products. Well, in the order of priority, obviously we'd use the licensed products first from the CDC. Those would be for A, B, and E if they were indicated, if it was the right serotype. Next would be the IND equine products probably and then last the human IND products that are available. Okay, that human products in short supply, I understand. Now the horse-derived products, the despeciated ones, would I still need to do sensitivity testing if I had a despeciated product or is it unimmunogenic enough that I could go? It's less likely to cause either serum sickness or anaphylaxis, but it's still important that you do the sensitivity testing beforehand. Okay, well we've talked now about post-exposure prophylaxis. Is there anything else we can do though to protect ourselves and perhaps prevent exposure in the first place to botulism? Well, like any of the other biological warfare agents, if you're aware of an impending release or a potentially impending release, a military gas mask is the best, obviously. We also did some work at USAMRA a number of years ago in which we tested some improvised masks. We used Army green t-shirts or brown t-shirt material as well as some handkerchief material and challenged some mice with either a big sticky globular toxin called ricin toxin by aerosol or with saxotoxin. And we found that two layers of either that t-shirt or the handkerchief protected mice against a very fine aerosol. This was 1.4 to 1.5 mass median diameter, so a respirable aerosol and the mice were protected by two layers. Now that doesn't necessarily say that humans would be protected nor could we ever really test this hypothesis in humans, but it suggests that an improvised mask system made of clothing of some kind or cloth or a tight-fitting painter's mask that you might be able to buy in a hardware store would certainly be worth trying if you were in a bind. Remember, however, that this would only work for the biological agents. For the chemical agents, you would need charcoal in that mask because a volatile would go right through that material. Just for the audience out there, we're not recommending you run around the chemical-biological battlefield without your mask, but on the other hand, if you are caught out there unawares, I guess worst case scenario, you fold your t-shirt on itself and hold that over your mouth that knows you might actually be protected against even small things like toxin molecules. Well, in addition to the botulism products, the antidotes that you have talked about, I understand there is a botulinum toxin vaccine that's currently an IND product, and I think it's useful to let the audience know out there that this vaccine was given to about 8,000 soldiers during Operation Desert Shield Desert Storm. You heard that 150,000 got anthrax vaccine, but about 8,000 got bot vaccine, and they were particularly soldiers who were deemed to be at high risk of botoxin exposure. In addition, it's routinely given at you, Samrid, to researchers who might be occupationally at risk of contacting botulinum toxins. The toxoid vaccine produces a serum antitoxin level that corresponds to a protective level in animal models. And I wonder if you had any comments on that, Colonel Frantz? Well, certainly I did a lot of botulinum work with both the vaccine and especially with the antitoxins, and based on all the animal work that I did, I found that if you have antibody on board when you're exposed to botulinum toxin, you're protected. Well, it's good to know. It's good to know, Colonel Frantz. You know, I sure appreciate your coming and all the input you've provided us once again this year. What I want to do now, though, is move on to another toxin called ricin. And we said that we would use botulism as our example of a military toxin. Ricin will be our example of a weapon of assassination. Thanks, Dad, I enjoyed it. Okay. A foreign diplomat has just negotiated a lucrative business deal with a large American corporation to revitalize his nation's economy. However, there are elements in his country who, for political reasons, don't want the deal to go through. They have chosen rather unusual means to eliminate the opposition. Okay, with me to discuss ricin, one of our toxinologists from USAMRA, Dr. Mark Poli. Dr. Poli, thanks for coming today. Thanks, Ted, it's good to be back. What is ricin, Mark, and why are we concerned about ricin as a biological weapon? Well, Ted, ricin's a protein toxin derived from the common castor bean. Once it enters the body and enters the cells, it very efficiently inhibits cellular protein synthesis. The primary cause for our concern is its worldwide availability. The castor bean plant can be found everywhere, and millions of tons are crushed annually to produce castor oil, which as you know makes an excellent industrial lubricant. The protein mash left over from the extraction process is about 3% to 5% ricin by weight, which makes it an excellent source of toxin. Extraction of the toxin from the waste mash is relatively trivial. As you know, there have been several instances where ricin's been used as a weapon of assassination. Let's look now at our next history video, and we'll learn a little bit more about ricin, I think, and potentially how it would be used as a weapon. Ricin gained notoriety as a terrorist weapon in 1978, when it was used against Georgi Markov, a Bulgarian exile and BBC announcer who broadcast anti-communist messages from London. On his way home, waiting for a bus, he was jabbed in the leg with an umbrella tip. This wasn't something that would appear all that unusual in a rainy city. Markov's wife recalls the covert attack. He came home on Thursday night, he was perfectly okay, and by the next day he was in a critical situation. When he came home on Thursday night, what did he say about what had happened to him? He told me the most extraordinary story that he'd been jabbed with an umbrella tip. It was almost as if he didn't want to believe it himself. Several days later, Markov was dead. The disguise weapon had discharged a tiny pellet containing the toxin ricin into his leg. The pellet was sealed in wax and designed to melt and release the toxin at body temperature. It was later discovered that this assassination was carried out by the Bulgarian communist government, and the technology to commit the crime was supplied by the Soviet Union. In 1995, another example involved Deborah Green, a physician who attempted to kill her husband with ricin during a dispute over custody of their children. He was hospitalized multiple times with an unusual illness that baffled his physicians. She ultimately burned down their house, killing two of their three children in the process. To this day, she has never revealed how she converted castor beans into a ricin-containing product. More recently, ricin has caught the attention of extremist organizations for assassination or murder plots because it's so easy to obtain and produce this agent. Mark, in what form would we likely encounter ricin? Well, it can be prepared either as an aqueous solution or it can be dried into a powder. Clearly, then, it could be disseminated as an aerosol over a large area or it could be used as a weapon of terror or assassination. You know, it seems that only minute amounts of ricin are needed to carry out an assassination, at least if you believe this Georgi Markov story. I would assume, though, that on the battlefield, one would need considerably more ricin. Can we do that? Yes. When you compare the potency of ricin to that of botulinum toxin or staph enterotoxins, it's clear that much more ricin will be necessary to aerosolize it over a battlefield-sized area. However, because of the millions of tons of castor beans being crushed every year, ricin is, in fact, easily available in such large amounts. Well, let's return now to our intrepid ACE doctors on clinical rounds. They're going to see yet another exotic and puzzling case. I wouldn't be surprised if it had something to do with ricin, but it appears to be all in a day's work for these guys. And I think you're going to particularly enjoy this case. Good morning, minister. The physicians are here to see you. Morning, minister. Minister, Dr. Cordepeter? Good day. Dr. Cislac? Hello, sir. Good day, doctor. I'm here to take a look at you, see how you're feeling, all right? Can you tell us what the latest is on him? Sure. It's febrile, temperature 101, heart rate 110 to 115, respiratory rate in the low 20s, blood pressure 100 over 60, and his urine output seems to be down. And it's pretty concentrated. Yeah, it's pretty concentrated. All right, and his ER sheet says his hematocrit's a little low. His white can is about 25,000. Sir, can you tell us what brought you to the hospital? What, when did you start feeling ill? I am honored to be the agricultural minister at Arbonia. We have developed a turnip that tastes like chicken. And this is city's business. This will be a revolution in the world's eating. Everyone will want this turnip. It is lower cholesterol, very healthy. Sir, sir, what? It will revive our economy. What brings you into the hospital, though, sir? The enemy of the people, they poisoned me trying to stop this turnip from coming to the market. I was yesterday planning my speech. An enemy hit me with an umbrella in my leg, and it bleed three, four hours later. He's got a nice puncture there. Three, four hours later, my heart fast. My hot temperature, and tired, very tired. All right, well, let me take a listen to your heart. Arbonian's healthy people must be poisoned. Go ahead, sit up for me. You said he was having a little bit of increased respiratory rate, too. He was having some trouble earlier. Deep breath for me. Anything out through your mouth? Nice big cough for me? OK, another deep breath. OK, you can lie back. He's got a little crackles there with the cough, but it's just tachycardic. I don't hear any murmurs or gallops or rubs or anything like that. I have a big pain here. Oh, yeah? Let's take a look. Yeah, the ER doc said he did have some adenopathy. He does, right, too. All right, let's go ahead and give him some oxygen, about two liters nasal cannula. You know, you probably should give him a fluid bowl of soul. So why don't you give him 500 cc's of ringer's lactate, run that in over an hour or two? And I think I'd turn up his rate to 150 cc's an hour. Well, is that 75 now? Right, right, I'd double it. All right, let's go ahead and get a full smack 20 on him, two sets of blood cultures, chest x-ray. And sir, do you have any allergies to medicines? Not, no. OK, good. Let's give him clindamycin 600 q8 hours. I'd be piggyback. Have you had a tetanus shot lately? Tetanus, very good. Tetanuski. Tetanuski, long time, long time. OK, well, let's go ahead and give him tetanus tip 30 booster. You know, you might as well get a talk screen, too. Why don't you send Yarn and serum for toxinology? Great talk screen, also. All right, sir, we'll hopefully get you feeling a little better. We'll give you some medicines. We must find what these enemies of the people do to me. All right. OK, sir, we will look into it, sir. Our economy depends on this. All right, it's nice to meet you. We'll let the ambassador know how you're doing, all right? Thank you very much. You take care. Thanks a lot. OK, sir. Minister, in a few minutes, I'm going to be back to put a dressing on. And if you could just tell him that we'll be back and we'll be in and out all day, OK? Yeah, I had to start that. Bruce, I'll buy you a baby machine, but I'm going to put it in the car. I'm not sure who's scarier, Ted, the assassin of that guy with the dark sunglasses. Well, I'd agree with you, Mark. For the people in the audience out there, it's important to, I think, understand that in this scenario, the Albanian agriculture minister had received a percutaneous dose of rice. But depending on the route of exposure, the clinical presentation could vary, and it could be equally baffling. For example, if you inhaled rice, and we have some information in that regard because there were some accidental sublethal exposures that occurred in some humans in the 1940s. But those patients who inhaled rice and developed symptomatology within four to eight hours. And those symptoms consisted of fever, chest tightness, cough, dyspnea, nausea, and arthralgias. And sometime later, those patients often went on to develop profuse sweating. And when they developed that, that seemed to herald the termination of most of their symptoms. Now, Mark, as a pediatrician, I've seen kids eat virtually anything one can imagine. For example, a kid who wouldn't dream of eating a Brussels sprout will down a whole can of kerosene. You've told us that castor beans are ubiquitous. The plants are common ornamentals everywhere. I can certainly envision kids getting hold of castor beans and eating them. Is that a problem? Oh, that's absolutely correct, Ted. Oral ingestion of ricin causes gastrointestinal hemorrhage with hepatic splenic and renal necrosis. Well, when it comes to treatment, I think everybody out there needs to understand that this is one of the diseases for which we don't have a specific antidote, like we did in the case of botulism. And we don't have antibiotic therapy. Obviously, this is a toxin-mediated disease, not a bacterial infection. And because of that, supportive care remains the mainstay of therapy in cases of ricin intoxication. And that supportive care would consist, in some cases, of respiratory support. So if the patient inhaled ricin, they were having respiratory symptoms, obviously you might need to provide them respiratory support. Many ricin victims can be vomiting profusely. And that leads to a couple of problems, to dehydration and to electrolyte imbalance. So if you ever have to deal with a ricin casualties, very, very important to pay close attention to their fluid volume status and their electrolyte status. Mark? Keep in mind, Ted, that the biggest difficulty with management of ricin intoxication is actually recognizing that it's occurred in the first place. An exposure to ricin involving a large number of individuals would probably be recognized epidemiologically, or perhaps we'd have input from intelligence sources. Specific immunological testing of serum or immunohistochemical analysis of tissue samples is available. OK, so for the folks out there, ricin is apparently extremely immunogenic. I would assume that acute and convalescent titers would be useful, would you agree? Yes, absolutely. OK, so I'm checking for antibody response. Now, are there any ways that we can protect ourselves from ricin before it's aerosolized or before it's delivered to us? Yes, the standard military protective mask is very effective. As Colonel Frans mentioned earlier in the program, a study with mice demonstrated that two layers of a t-shirt or a handkerchief protected mice from an aerosol challenge. While I'd hesitate to make any definitive recommendations based upon such a small study, it does suggest that in the absence of a mask, folding your handkerchief, your t-shirt over your nose and mouth might confer significant protection during an aerosol attack. OK, so that's fine if the release is known, if I know a release is coming. Is there anything I can do to protect myself from an unknown threat? Well, we do rely heavily upon our intelligence community for information and threat analysis. We do, in fact, have a candidate ricin vaccine, which is in the pipeline, and it's been shown to protect animals from a lethal exposure. OK, well, Mark, thanks once again for joining us this year. This is, I think, your third year on the broadcast as well. And that ends our discussion of the five major representative agents. Thanks for sticking with us. We've made it to the home stretch. We're now going to go to our site activity for the day. If you'll turn to page five of your student booklet, you can follow along as we roll the scenario. Now, after the scenario is finished, we're going to go to the audience and answer the first three questions, and then we'll take some questions from callers out there in television land. If we have time following our site activity, we'll try to answer a few more facts as I think time may preclude us doing that today. If we don't get a chance to answer more facts as today, we'll try our best to make time tomorrow. So, OK, is everyone ready out there? Go to work. We'll see you back in about five minutes. Hello, everybody. Hi, I'm Dr. Richards. Dr., thank you for coming. Sure. Hi, kids. What's going on? Wow, look at those big bumps. Yeah, my kids are really sick. Started about three or four days ago. They got really high fevers. They've been throwing up. They say their backs have been hurting them. And a couple of days ago, they developed these really horrible bumps. It's like chicken pox. Chicken pox? No, Jill had the chicken pox when she was three, and Michael already had the vaccine. Well, the vaccine isn't always 100%. How high have their fevers been? 102, 103. And did they go to school or maybe see kids in the neighborhood that may have had chicken pox? Not that I know of, kids. Any of your friends or anyone that you've been playing with have a chicken pox? I wonder why they both came down with it at the same time. Can you remember what you were doing about two weeks ago when they might have been exposed? Two weeks ago, let's see. That was the 4th of July weekend. We went down to the mall to see the fireworks. Do you think that we were exposed to someone with a chicken pox down there? Well, there are a few thousand people who go down to the mall for 4th of July. I don't know. I guess that's the possibility. But they could have been exposed any number of places, huh? Excuse me, Dr. Richards. Yes. Can I talk to you for a minute? Sure. Excuse me. I just want to let you know where I'm going to be. I'm going to be up in the ICU admitting a patient. A young night-to-duty soldier. I don't even feel the exercise. Came in a ton, dude, lethargic, horrible disfiguring rash all over his body. Sounds pretty sick. What do you think it is? Well, looking at the lesions, I'm really not sure. I wonder if it's typhoid fever. I already thought about something like, I don't know, Rocky Mountain Spotted Fever or maybe Tyvis. I suppose those are possibilities, too. I'll have to see what pans out. Yeah. I've got a couple of kids in here right now. They're not that sick. But have you ever run across a case of recurrent chicken pox? I haven't personally. Colleagues of mine tell me sometimes what happens is that the mother will misinterpret that initial illness is chicken pox when, in fact, it's something else. So this very well could be the initial presentation. Right. Well, as I said, I don't think they're that sick. I'll send them home. Thanks for letting me know where I can reach you. I might come up and take a look at that rash later. That sounds great. Thanks. All right, sorry about that interruption. Well, it wouldn't be unheard of for the kids to get chicken pox a second time, although it is somewhat unusual. But I'm really not that concerned about it. Just take them home and make sure they don't see any other kids for about a week. We'll let these lesions crust over, and then I think they'll be all right, OK? Now, listen, kids, I don't want you to scratch those bumps on your face, OK? Because that could leave a scar, and we don't want that to happen. Yes? Excuse me, sir. I just got a call from Fort Mead. And I really need to talk to you as soon as you get a chance here. All right. So if you have any other concerns, please call me back or bring the kids back in, OK? So long. Take care, kids. Have a nice summer, OK? Yeah, what's up? Sir, that was Fort Mead. Now, they say that they have a whole company of soldiers that have come down with chicken pox. Now, some of these soldiers are very sick, and they're all coming this way. It's bizarre, all these cases in the same day. Make a preventive medicine on the phone. Yeah, hi, Joe. This is Walt Richards in the clinic. Listen, I just heard about an entire company of soldiers headed over here with chicken pox. You're kidding, 1,000? All right, thanks. OK. Sir, what's going on? He says that almost every hospital within 100 miles of here is reported chicken pox today. Over 1,000 cases so far. 1,000? Trace them all back to the 4th of July on the mall. Public health department thinks it might be an intentional event. Intentional? Intentional? Listen, don't let these kids leave that room, all right? I'm going up to ICU. Move these patients down to the other waiting area. Right away. OK, well, I know we haven't given you much time to work on this site activity, but let's see how sharp you really are. Let's go right to the questions. First question is, what's the diagnosis? Anyone know what's going on here? Smallpox. Smallpox, OK. And you see how easy this is. You've had 30 minutes worth of training in smallpox. I venture you've never seen a case, and yet you made the diagnosis like that. And again, it's really that easy if you have that index of clinical suspicion. Now, we're in a biological warfare course. Everyone's thinking biological warfare. In that context, it's easy. If you're that good three years from now, when all this is a distant memory, you'll be biological warfare defense doc or nurse extraordinaire. OK, question number two. What control measures would you institute? What would be appropriate in this case? Anyone? Ma'am? Quarantine and respiratory protection. OK, great. So we don't usually use that dirty word quarantine much anymore, but I guarantee if we ever saw smallpox again, that would be the one disease that we would definitely want to quarantine. And there's a lot more information on quarantine that's going to be discussed on day three of this program, I think, by the CDC people. OK, next question is, we think it's smallpox, but we need to confirm it. Before anyone unleashes the retaliatory response here, they're going to need confirmation. So how do we make a diagnosis? How do we cement a diagnosis of smallpox? Anyone? PCR work? OK, PCR, great. We talked about PCR and viral culture. Those are certainly the gold standards. Again, we said, don't try this at home. Very few laboratories in this country are going to have the ability to do smallpox, PCR. But PCR and viral culture would definitely be the gold standard. Anything else you could do? Electron microscopy. OK, you could do electron microscopy. Again, don't necessarily try this at home. Electron microscopy wouldn't tell you that this is smallpox, but it certainly would tell you that this is an orthopox virus. Aren't too many human orthopoxes indigenous to the United States. Anything else one might do? Dr. Henredig. Since chickenpox was in the differential, they could do the readily available Zanx smear, and that should be negative. Great, and that's one thing as a pediatrician that I could probably do. I might not be able to do electron microscopy, but I could probably get a Zanx smear. And if that Zanx smear was negative, at least I'd feel a little more comfortable that maybe this isn't chickenpox. Maybe this is something more sinister. OK, next question, and I think we'll try to get some answers from the audience out there in television land if any of them dare call in. OK, what treatment would you recommend for smallpox? And the little voice in my head is telling me that we have an answer from General Leonard Wood Army Community Hospital at Fort Leonard Wood, Fort Lost in the Woods, Missouri, home of the chemical corps. So if we can go to Fort Leonard Wood. Hello. Yes, what treatment would you recommend for the patients seen in this scenario? Well, most of the treatment would be probably supportive. There's really not much treatment you could give them, you know, antibiotics or otherwise. OK, well, I agree 100%. If you're dealing with patients who already have clinical disease, then there's probably no good treatment other than supportive care. And in the day when smallpox roamed the earth, it had a 30% fatality rate. So if your cup is half full kind of guy, you can probably achieve a 70% cure rate or recovery rate with supportive care. If you can catch those people before they become symptomatic, then there is post-exposure prophylaxis. Great job. Let's go to the next question. Who can assist with outbreak investigation? Who might you call? Fort Leonard Wood? I'm still here. You could probably call the CDC or maybe your department or whatever it is there. OK, a great answer. And again, we all hope that we never have to deal with this disease again, as Dr. Henderson, I think, made clear. But I guarantee that the CDC would have a battalion of EIS officers on your doorstep instantly if you really thought you had smallpox. So no problem calling the CDC. Now, sixth and final question. How do you contact your health department? Let's say you want to follow the proper chain. You want to go to the health department before you go to the federal guys, the CDC. How do you get in touch with the health department? I guess I pick up my phone book and look at the telephone number. OK. OK, I'll buy that. And the CDC, I just want to take this opportunity to make a plug. The Centers for Disease Control is going to go over again in great detail how one would work up a civilian bioterrorist incident on the third day of the show. So again, we would encourage all the civilians and the military members in our audience to watch all three days of the show. And I think that question will be answered to a great degree on day three of the show. Well, we are running out of time rapidly. It's been a great day. You've been a great audience. I think we've learned a lot. We've covered a lot. Again, we haven't covered every individual agent. But I think if you understand the five agents we've covered, you will be able to generalize that knowledge. I think now it's time to review some of what we've learned today in the last few minutes that we have left. So if we can go to the review segment of today's show and take it from there. Okay, well, you've almost made it through day one of the program. Again, today we've covered five of the most significant biological agents. And those agents represent the various classes of bacteria, both spore-forming and vegetative, viruses, and toxins. I think Denise wanted to clarify one thing before we go. You're telling me, Denise, that for smallpox do you want them to go? Well, I think the only thing that we would want to make a point from the public health perspective is that the local and state health department are right there. We do have, I mean, the CDC would most likely, I would think, in the case of a smallpox event, be invited in. But really, they're going to be the ones who are right there on the scene. Really, they need to be called first. And all these chains will proceed presumably simultaneously. So you want them to follow the chain of command. They should go to a local health department who would then go to the state who would then go to the CDC. I assume that would all happen pretty quickly. In smallpox immediately. It's not going to be just true for smallpox. It's going to be true for all of these diseases we've talked about today. Well, great, thanks. OK, before we close now, we want to give you some highlights of what's going to happen over the next two days. Now, tomorrow, as I've said before, we're going to use a military outbreak scenario to carry you from the initial presentation of ill patients all the way through treatment and evacuation from the theater. In that discussion, we'll talk about sampling methods. We'll discuss epidemiologic issues, how to investigate an outbreak, how to make a diagnosis, various techniques available for diagnostics, infection control, and even mortuary affairs and evacuation issues. Ali, tell us about day three. Well, on day three, we're going to talk about some of these issues also, mainly from a public health standpoint. And what we'll be doing is using real scenarios and some simulated scenarios to help you understand what is the role of public health in handling a civilian bioterrorist event. We think the next two days of our broadcasts have elements in them that will be useful for everyone. So we encourage all of you to watch the entire rest of the program. However, we understand that you have many time commitments and must determine what's the most useful training for you. So therefore, remember that you have the option of tuning in for only one, two, or all three days. Don't forget, in order to receive the CME credits or CNE credits or CEUs, you must complete the exam for each day of the course you attended. But do this only after you've finished watching everything that you intend to watch. So if today is going to be the only day that you can watch, go ahead and take today's test before you go home tonight while the information is still fresh in your mind. But if you're coming back, don't take the exam until after viewing the last day that you intend to view. With that, we wish you a pleasant evening. We look forward to seeing all of you or as many of you as possible again tomorrow. So for Ali and Denise and myself, again, good night.