 Today, on Tuesday, we're going to talk about bacteria, and in the coming days, we'll talk about the viruses and the toxins. As most of you, I'm sure, realize, bacteria are unicellular, ubiquitous organisms that cause disease in plants, animals, and humans. Certain bacteria have certain specific traits, high virulence, good stability in the atmosphere, good dispersibility, et cetera, that make them viable biological weapons candidates. Some of the foremost agents, which possesses virtually all of these ideal traits, and the one, of course, that's in the news a lot today, is the queen mother of biological warfare agents, anthrax. Okay, what is anthrax? Well, anthrax doris is a disease caused by infection with a gram-positive spore-forming rod, bacillus anthracis, and anthrax is in most military medical planner's opinions probably the single greatest warfare threat. Certainly many countries have worked on it. In the past, Iraq and the former Soviet Union are notable examples. We know that anthrax can be a very valid aerosol threat. Not only do we know that from animal experiments, but from a very real occurrence that happened in 1979 in the former Soviet Union. There were rumors initially of an outbreak in and around the town of Svedlovsk in the Soviet Union. These rumors initially trickled out to Western intelligence agencies. When it was all said and done, it turns out that a leak occurred at a military microbiology facility in Svedlovsk, and depending on your accounting system anywhere from 66 on up where patients actually died of aerosolized anthrax. Okay. Well, I'd like to say thank you very much to Dr. Perkins and Colonel Kelly for being here with us today. We now have quite an interesting interview with Professor Matthew Messelson from Harvard University, who with Dr. Gene Gilliman led an investigation of that incident. Let's take a look at the videotape. Sometime during the day on Monday, April the 2nd, 1979, an aerosol of bacillus anthracis anthrax spores escaped from a military microbiological facility in the city of Svedlovsk in the Soviet Union, about 900 miles east of Moscow. And this cloud drifted downwind and infected people and animals. The people who were infected were almost all within a very narrow zone that went from the military microbiological facility, which was in the southern part of the city, down to the southern city limits. And then for almost 50 kilometers more, villages had dead sheep from anthrax infection and a few dead cows. No people were infected outside of the city. We know this because although initially when I went the first time to Svedlovsk, I thought that of the two hypotheses, one that it was food-borne and two that it was airborne, that it was still quite plausible that it was food-borne. But there's nothing like data to decide between two hypotheses. And when we found, after two years of interviewing of families of those who died, that the people who died worked in factories and other places that were in a very narrow zone. And when we found that the six villages which reported dead sheep were all on a straight line, the same line that was the center zone of where the people were to died. And when we found that on Monday, April 2nd, that the wind direction as recorded by the local airport was exactly in that same direction all day long, then it was obvious that this had been an airborne release. There was previous patho-anatomical evidence, suggestive that it was inhalation anthrax. But the problem with that evidence is that we don't have any good patho-anatomical reports of true gastrointestinal anthrax. And so a differential patho-anatomic diagnosis, rigorously speaking, is not possible without that further evidence. However, it was suggestive from the fact that there was more involvement of medistinal and thoracic nodes than of mesentery nodes, although there was also involvement of meningitis. It was suggestive that it was inhalation, but it was epidemiology that not only solved it, but also told us when it happened during the day on April 2nd and where it came from, the military microbiological facility, something that of course autopsy couldn't tell you. As to how the infection was first identified as anthrax, I can only tell you what people told us. When we interviewed the former epidemiologists of the city, he said that as soon as they realized that there was an unusual epidemic, they tried to narrow it down. They considered plague, smallpox, anthrax, and maybe tularemia, I don't remember. The first identification of it as anthrax, if the stories we were told are correct, was due to the pathologist Abramova who saw the extensive hemorrhage in anthrax meningitis once in a textbook. That condition is called Cardinal's Cap because the entire meninges are hemorrhagic. She saw that in one of the patients and remembered the textbook that she had seen earlier, years earlier, and according to what we were told by the various medical people we spoke to, that was the first tentative diagnosis and then material was sent to the bacteriological lab and the next day, the tenth, if the dates that we were told are correct, the tenth of April, you got a confirmatory report back from the bacteriological lab and from then on it was anthrax. And then posters were put up in the city, in the southern part of the city saying, dear citizens, you are invited to be inoculated against anthrax, they called it Sibir Skyo Yasne, Siberian ulcer. You were invited and they vaccinated 50,000 people. There's an immense amount to be learned from each epidemic of this sort and one should not let such an epidemic go unstudied because, for example, from this we learned that although up till then it was only theoretical that it's really true that an anthrax cloud can remain infectious, 50 kilometers downwind. Before that you could have said, well, maybe there's something in the atmosphere that we don't know about that will kill the spores. Well, it didn't happen there. There was one other remarkable thing that we learned from this and that was that amongst the 68 people who were reported to have died and we had information on the majority of them, nobody was younger than 24 years old. No infants, no babies, no children, no adolescents, no young adults. A big surprise when we looked into the old literature on inhalation anthrax, of which there are a number of reports, including quite a few from Russia, from Tsarist and post-revolutionary times, we also found that there were no young people. Now whether that really means that young people are less susceptible to inhalation anthrax and perhaps to other inhalation infections is a very important lead and we would never have asked this question if we hadn't done the epidemiology and we still don't know the answer. But there's another example of how epidemiology can not only tell you what happened in a given case but can bring up new questions, perhaps very important new questions, for future research. Well, that was fascinating and it certainly emphasized the importance of epidemiology. But tell us some more about anthrax, Ted, and does it occur naturally? Well, Doris, before I answer that question, I'd like to welcome Colonel Art Freedlander here, one of the world's foremost experts on anthrax and the senior military scientist at USAMRAID, as well as my boss, Colonel Ed Eitzen, who's Chief of the Operational Medicine Division at USAMRAID. Maybe Colonel Freedlander would probably be best suited to answer that question. Sure. Well, anthrax is a naturally occurring disease. It's a zoonotic disease of herbivores and that means domesticated animals, such as sheep, cattle, goats, and also wildlife. It occurs throughout the world, which is indicative of the fact that the spore does occur in the soil throughout the world. Now humans become infected under natural circumstances by contact with infected animals or contaminated animal products such as wool or hair or hides or bone meal. By either the cutaneous, the gastrointestinal, or the respiratory root. And here we can see a picture, I think that's coming forth of a rhinoceros. This is actually an endangered species in the national parts of South Africa. And one of the problems facing these rhinoceros is anthrax, in fact. I think the next slide shows a zebra, again, wildlife threatened by anthrax. You know, Doris anthrax is, as we alluded to earlier, an organism that's found in the soil in many parts of the world. Now it's not quite so common in the United States, but in Iran, Pakistan, Afghanistan, many of the new republics of former Soviet Central Asia, and in parts of sub-Saharan Africa, anthrax is very, very common. And even in the United States, there are areas of the country where one does see a heavy anthrax contamination of soil. Texas, Oklahoma, the Dakotas, for example. Here's a cow, in fact, in Texas. And I show this picture in honor of Colonel Parker, my boss. Colonel Parker is an Aggie, a graduate of Texas A&M University. And this is a Texas longhorn. And Bevo here has succumbed to anthrax. He's given the Hookham Horns a sign there. Colonel Friedlander, though. How does anthrax cause disease? Well, what happens is that the spore is the infectious form of the organism. And the spore enters the host. And then the spore germinates. That is into a bacillus, a rod-like shape of the organism. And the organism then has the capacity to produce two toxins, the so-called edema toxin and lethal toxin, as well as a capsule. And the toxins interfere with the host's response to the organism. And one of the key roles of the key players in the toxin is a so-called protective antigen. But it's the toxins that cause local damage to the tissues and the capsule that interferes with phagocytosis of the organism that enables the organism to survive in the host. Okay, Colonel, how does this translate to presentation of the disease? Well, Doris, it depends on the route of exposure. The most common form of anthrax is the cutaneous variety, which causes over 95% of naturally occurring cases of anthrax. And this is caused by spores entering breaks in the skin of the person infected. There is a natural progression of the lesion of anthrax from papule to vesicle to an ulcer to a black escar. Now, the first picture you saw was a papule. This is a vesicle form of the disease. And this is followed by ulceration as seen in this photo. Finally, by escar formation as seen here, which is a necrotic central area of the lesion. Also, the organism produces quite a bit of edema in some lesions. As in this next picture of a Haitian child, you can see the lesion on the Haitian child's lower eyelid and quite a bit of edema caused by the edema toxin that the organism produces. Sometimes this can be very, very pronounced. The case fatality rate of cutaneous anthrax is 20% without treatment and less than 1% of cases if appropriate treatment is given. Carl Friedlander, what is the treatment of choice? Well, the treatment of choice is penicillin. This is for naturally occurring anthrax since essentially all strains are sensitive to penicillin. However, in the context in which we're discussing this today, that is in biological terrorism, we have to consider the possibility that it may be resistant to penicillin. And in that case, one would consider using a fluoroquinolone such as ciprofloxacin or tetracycline such as doxycycline. Ted, what other forms of anthrax are there? Well, in addition to the aerosol form of anthrax and the cutaneous form of anthrax that we've just discussed, there is a third form, gastrointestinal anthrax. It's a very rare way for anthrax to develop. And probably the reason it's so rare is that you have to get it by eating contaminated meat. And usually anthrax is a pretty rapid, pretty messy death. And most animals that would die of anthrax probably wouldn't be butchered for human consumption. So again, pretty rare way to get anthrax. But when you do see those rare cases of gastrointestinal anthrax, the pathophysiology is somewhat analogous to that scene in the other forms. In other words, it's a lymph adenitis, a hemorrhagic lymph adenitis. And here on the screen, you see a picture of those hemorrhagic mesenteric lymph nodes. So somewhat analogous to the lesions you'd see in the other forms of the disease. Okay, Colonel Itzel, what would be the most effective way to disseminate anthrax as a BW weapon? Well, Doris, the best way is through aerosol dissemination. Remember the subway scenario we just saw. One can affect more people by disseminating the organism by aerosol than any other way. Also, anthrax is most deadly by the inhalational route. The case fatality rate for inhalational anthrax is quoted by a variety of sources as between 80 and 100% of cases fatal in people who are exposed to an effective dose of the organism. Colonel Friedlander, what about the incubation period? Well, the incubation period for inhalational anthrax is from about one to six days. There's actually limited information about this disease. It's a rare disease. And it presents with a flu-like illness of malaise, some fever, nonproductive cough. This, there may be a period of improvement and over the next day or two, it progresses to really the sudden onset of respiratory distress. This is marked then by some chest compression symptoms, pain in the chest, and stridor, so that there may be a change in the voice. And this is probably at the point where the disease, as we discussed, is spreading from the lymph nodes in the chest to the mediastinum. These severe respiratory symptoms then will progress over the next day or two with spread into the bloodstream of toxemia and eventually hypertension and death within 24 to 36 hours. But at the outset, it doesn't sound like it's anything other than the flu. I mean, how do you tell the difference? Well, Doris, that's a good point. And that's a very valid point, because that's exactly what happens. At the outset, it doesn't look very different from the flu, and that's what makes it a tough disease to diagnose. And unfortunately, you have to do that diagnosis early on. So it's going to be a big, big problem for us. The physical findings in early stages of anthrax are nonspecific. As you get into the later stages, the chest x-ray may show a wide mediastinum. Again, and you can see that here, but that's late in the course of the illness. So if I saw that in a patient, I'm probably not going to be able to salvage that patient. But I do hope that I can use that knowledge and use that to salvage other patients who may have been exposed to the same thing. Same thing goes for Gramstain. Gramstain of blood may show organisms, but again, not until late in the course of illness. And I'm probably not going to salvage the patient who already has a positive peripheral blood, Gramstain. But I do hope that by diagnosing that severe case, I can be then armed with that knowledge and use it to help other cases out there on the battlefield or in our cities and towns. Hemorrhagic pleural effusions tend to occur late in the case of anthrax cases. And in 50% of cases, there's a terminal hemorrhagic meningitis as well. All right. Colonel Freedlander, how is anthrax weaponized for biological agent use and what makes it such a good biological weapon? Well, what makes it a good weapon is the fact that there are two features. One is that it's stable as an aerosol and it is naturally infectious as an aerosol. This is a natural form of the disease and its physical characteristics in terms of stability and infectivity. And its size, its particle size, make it essentially an ideal weapon. That is, the one to five micron particle size is such, as you've heard before, that it will be deposited and retained in the alveoli of the lung deep within the recesses of the lung. So then after you inhale anthrax, what does it do to the body? Well, I think we have a video clip that will demonstrate that quite nicely. Once you inhale anthrax spores, those spores get down into the lungs. They're taken up by white blood cells in the lungs, pulmonary macrophages. Those macrophages do their job in the sense that they take up the spores, but they have a difficult time killing those spores initially. And so they end up serving as taxi cabs and transporting those spores to the nearest regional lymph node. And it's in the milieu of that regional lymph node that anthrax really flourishes. So once it's in the lymph node, the anthrax vegetates, comes out of its spore form, into its vegetative form, starts reproducing, cranking out its toxins. The lymph node becomes necrotic and eventually breaks down. And from there, the anthrax bacteria get into the bloodstream circulate around to affect the rest of the body. And I think, in fact, we may have a shot here of viable anthrax organisms clogging up a terminal blood vessel. I believe this is a scanning electron micrograph of a terminal arterial. And you can see here at the time of death, it is absolutely chock full of viable bacillus anthracis organisms. And one of our basic scientists estimated to me that at the time of death, 28% of the dry weight of blood is viable bacillus anthracis organisms. Not difficult, I think, for the clinician out there to realize why you don't stand much chance of success if you wait to treat these patients. They need to be treated at the very earliest opportunity. Okay, is inhalation anthrax treatable? Colonel Watson. Well, Doris, as I mentioned before, cutaneous cases are readily treatable with penicillin. And in fact, only one naturally occurring case of penicillin resistant anthrax has ever been documented. For inhalational cases, however, treatment can be very difficult, much more difficult. And in fact, you need to treat inhalational anthrax very early and very aggressively. Still, even at Sferdlosk in the Russian outbreak, some cases were treated with antibiotics and survived. Colonel Friedlander, based on what you've seen with the animal challenge studies, what would you recommend for treatment? Well, I should first say that there's really minimal experience with treating this disease in humans because of its rarity. And we have had an opportunity to look at non-human primate models of inhalational anthrax. And based upon those studies, as well as in vitro sensitivities, the recommendations, and I think they'll be on the screen, is that if it's a penicillin-sensitive organism to use high-dose penicillin, and here we're talking about 20, 24 million units of penicillin a day. However, again, in the context of what we're discussing, if it's a penicillin-resistant organism or if you don't know the sensitivities, we would recommend a fluoroquinolone or a tetracycline given intravenously to manage this disease. Right. Well, how do you protect yourself and other people? I mean, isn't this a contagious disease? No, Doris, it's not. In fact, if there's any good news attendant to this whole problem of anthrax, it's the fact that it's not contagious person to person. In fact, I'm not aware of any person-to-person transmission of anthrax. The last large-scale human outbreak of anthrax occurred in Zimbabwe in about 1979. There was the possibility that during that outbreak there was some transmission from person to person via a biting fly vector. But in general, that's a pretty unusual way to transmit anthrax. And this brings us to this whole issue of precautions. And the CDC has recently revised its guidelines and used new terminology. But now we would consider standard precautions, what used to be called universal precautions, as sufficient for managing patients with anthrax. Professor Friedlander, where is there an area of concern? Well, one of the areas of concern, and I think Mr. Patrick discussed that earlier, was the question of the contaminated environment and what to do with that. There's no good evidence in humans of infectivity from secondary aerosols with anthrax spores. Nevertheless, we think that it would be prudent, certainly in the immediate area of a munition that went off, where there might be high levels of spores, to avoid the area until it was decontaminated. And the same argument would go for exposed patients, although again we do not think that's really a significant hazard. But soap and water and dilute bleach should certainly handle that situation. Now, besides protecting yourself from becoming exposed to the spores, what can you do to prevent the disease? Well, Doris, the best way is with immunization using the anthrax vaccine. And in fact, through animal and human vaccination programs, we've been able to decrease the numbers of anthrax cases now in the U.S., to the point that most people now think that anthrax is a new disease, when in fact, as Ted has described, it's been around since antiquity. Well, what happens if you're exposed to aerosol anthrax and what do you do? Well, if you've been exposed, there are two approaches that are necessary. One is antibiotic prophylaxis. And I think again we'll see what some of the recommendations are coming forth on the screen. But that would include again use of antibiotics such as ciprofloxacin or doxycycline for a period of four weeks, plus the beginning of vaccination. And that would require three doses over a four-week period. And the reason for this is because of the fact that the spore can persist in the body for a prolonged period of time. So that's the reason to have combined antibiotics plus vaccination. Now, if vaccine is not available, we would recommend that the treatment with antibiotics should be prolonged to about 60 days. Because as I've said, there have been cases that have occurred quite long after exposure. You know, Doris, a whole lot of triage issues are called into play here. If you had very few cases and plenty of medical resources and there were an anthrax exposure, of course, you're going to treat everybody. Even people who are vaccinated are probably going to get 30 days worth of post-exposure prophylaxis. On the other hand, if resources are limited and large numbers of cases are occurring, of course, you're going to start triaging those patients. And those people who are fully vaccinated will probably last in line to get post-exposure antibiotic prophylaxis. All right. Well, before we start our discussion on the anthrax vaccination program, we have an interview with Dr. Rick Spiegel from the CDC, describing the decrease in numbers of anthrax cases. So let's take a look at that. Probably the most effective intervention in reducing anthrax in humans has been the initiation in many, many countries of effective animal vaccination programs. And these have proven to both stop epidemics of anthrax and prevent epidemics of anthrax from occurring. There are some states that are more highly endemic for animal anthrax. And in those states, for example, one notable state might be Texas. There is a high knowledge of anthrax as an animal health problem. And as such, they vaccinate more often there, as well as in other states, Texas, Louisiana, Oklahoma, South Dakota, North Dakota. Those would be some of the notable states where anthrax is known to be an animal disease, and therefore known to be a risk of human disease as well. The worldwide control of anthrax, probably the most important intervention that has taken place, has been the widespread institution of the Stern animal vaccine. In areas of high endemicity, the Stern vaccine, which is a live bacterial spore vaccine of bacillus anthraxus, has been remarkably effective in reducing the number of epidemics that have occurred in animals, and in addition, the number of cases that have occurred in people. In other settings, such as the industrial setting, the human vaccine has been widely used. And this is a cell-free filtrate vaccine, which is totally different than the animal vaccine. But again, has been very, very effective in reducing the number of cases of industrial anthrax that have been, that have developed. Well, most of you, most of you have heard about the anthrax vaccine, especially if you're in the military, and we're very fortunate today to have Colonel Roger Opio here. And Colonel Opio is responsible for the implementation of the anthrax vaccine implementation plan. Colonel Opio is the current chief of operations at US Army Medcom, and welcome Colonel Opio. Thanks, Ted. Great to be here. Well, the threat of anthrax, I think everyone realizes, is certainly a great threat. And in fact, in 1970, the World Health Organization conducted a pretty frightening study and they assumed a bad guy was armed with 50 kilograms of various agents and was able to spread those agents along a two kilometer front upwind of a city of 500,000. And they looked at several putative agents, and amongst those was anthrax. And by far, anthrax presented the most frightening scenario, a scenario where there would have been at least 125,000 total casualties, 95,000 of whom would have died. I think given this, we can all see why the Department of Defense is so eager to step off on an anthrax vaccination program. And I wonder if, Colonel Opio, you could shed a little bit more light on this program. Sure. As Dr. Sue Bailey indicated this morning, it was truly a landmark decision that was made by the Department of Defense to start an immunization program to make sure that these threats that we've discussed earlier today are in fact in place for those that are the most at risk. We can see that the analysis has been done through the intelligence community and we have developed an implementation plan that will be executed over the next five years. A very fast moving train from January 97 when the Secretary of Defense came up with the implementation plan, HA supplement that with a tracking system because of the nature of the immunizations, and then finally an execute order given by Secretary Cohen. And so this has been a very fast moving track and truly a landmark decision, as she indicated. The Secretary of the Army has been designated as Executive Agent for this with the Surgeon General responsible for the implementation of the program. A timetable was quickly developed and as you see on your screen, we are in fact a three-phase operation. We have in fact started with the 2 March deployment to Southwest Asia and we have immunized about 40,000 individuals during that phase. We're currently, as of 9 September, started in Korea and currently we have about 25,000 out of the total population that are currently immunized as of today. And by that, I mean that we have a recording of those immunizations actually into our data bank, a truly remarkable achievement. This is a thoroughly thought out program, it wasn't rushed to, it was even though the program has been in existence through the FDA with approved vaccine for over 28 years, we have in fact gone through self-mown testing, we've had an automation tracking system put in place and then we've had an independent review. So it's very well thought out and I think is a very well executed program. I know as I travel around the country teaching bio warfare defense to various medical practitioners, I certainly hear a lot of concerns from soldiers in the field about the safety of this vaccine. I think you've pretty much allayed most of those concerns here today. Well, has the vaccine ever, has it been used before? Yes, it has. And in fact, the current anthrax vaccine has been licensed since 1970. So it's been used for over 20 years. It is prepared from a filtrate of a culture of an attenuated avirulant strain of anthrax bacteria. It doesn't contain any live agent and it is not capable of transmitting the disease to humans. It has been used historically by workers who handle animal products and also by laboratory personnel. As you heard from Dr. Spiegel from the CDC, both the animal vaccine and the human vaccine have been very effective in reducing cases of anthrax. The vaccine was given to about 150,000 soldiers during Operation Desert Shield Desert Storm or about 25% of the total force deployed during that operation. And no severe adverse health effects were seen during that time. Well, Ed, I've had my six doses of anthrax vaccine. I didn't have any side effects. And in fact, I've distributed many doses of anthrax vaccine. I'm really not aware of anything other than some minor side effects. How about you? Are you aware of any significant problems with this vaccine? Well, Ted, clinical studies submitted to the FDA for the original licensure of this vaccine contained information on about 16,500 doses that had been given. Mild local reactions consisting of redness and tenderness at the vaccine site occurred in about 5% of recipients during the initial series and about 3% to 16% of those who received boosters. Moderate reactions with redness 1 to 2 inches in diameter with tenderness or itching at the site of the vaccination were reported for less than 1 to 3% of all the doses that were administered. Severe reactions consisting of marked tenderness or limitation of arm motion were reported in less than 1% of recipients. So these reactions are unusual. Local reactions usually resolve within 1 to 3 days except for some vaccinees who may develop a non-tender subcutaneous nodule shown here. And these little nodules that occur in the subcutaneous tissue can last up to two months but resolve usually without treatment. The biggest problem associated with one of these nodules is to have a surgeon around who doesn't have enough to do it. Only four systemic reactions were ever reported in the original licensure data with fever, chills, body aches for up to 24 hours. So systemic reactions with this vaccine are very rare. There has never been any evidence of any long-term side effects of any significance associated with use of this vaccine. Well, Colonel Einstein, is there a formal reporting system for something that you wouldn't expect to see? Yes, Doris, there is. And in fact, any severe reactions should be documented in the patient's medical record. Any reactions resulting in hospitalization or lost time from duty, and we define that as greater than 24 hours lost time from duty, should be reported on a form called a vaccine adverse events reporting system form or VAERS 1 form. Anyone with a hypersensitivity reaction such as anaphylaxis should have that marked in their medical record very clearly and they should not receive any further doses of this vaccine. Colonel Friedlander, does this vaccine work and is it effective? Well, first of all, there's very limited data on the efficacy in humans. There was a field trial done using a similar vaccine in the 1950s in wool mill workers in the northeast of the U.S. And in that study, it was demonstrated that the vaccine was effective in preventing cutaneous anthrax. There was a 93% protection rate against the cutaneous form of the disease, which is the form of the disease that usually occurred in the mill workers. However, there were some cases of inhalational anthrax that occurred during this outbreak. And as it turned out, there were five cases, all five cases occurred in the group which did not receive the vaccine. There were no cases that occurred in those workers that were vaccinated. However, so while it suggested that the vaccine protected against inhalational anthrax, the number of cases was not sufficient to offer statistically significant proof of efficacy. And that's the only data that exists in humans and hopefully we will never have any more data. But part of that, for that reason, the vaccine efficacy was tested in the best model we have, which is in the non-human primate. And in such studies involving rhesus monkeys, it was demonstrated that after receiving in 25 monkeys, and I think you can see this on the screen, who received two doses of the vaccine, all 25 monkeys survived. Now, there were also, and this is from a period from two to nine months after vaccination, in fact, seven of eight monkeys survived for a period of two years. In an additional study, there were 10 monkeys that received only a single dose of the vaccine, and all 10 of those survived. So that with the best animal model that we have for this disease, inhalational anthrax, the vaccine is highly effective with 42 out of 43 monkeys surviving. You know, those studies are certainly pretty comforting. Of course, with any vaccine, there are going to be some contraindications, and I wonder if you could elaborate upon some of those contraindications with respect to anthrax vaccine. Sure, Ted. As you know, personnel who have a hypersensitivity reaction with this vaccine, even though hypersensitivity reactions are quite rare, should not have a further dose of the vaccine. Those known to be HIV positive or otherwise immunocompromised should not be vaccinated as they are not deployable anyway. There also are some temporary conditions, as shown on your screen here, during which vaccinations should be deferred. And those include an acute respiratory disease or other active infection. Those with a temporary suppression of their immune system, such as a patient on corticosteroids, and those who are pregnant. You know, Ed, again, as I travel around, one of the things that causes great concern, and one of the questions, I guess, that comes up frequently, is the question of pregnancy. Are there contraindications to giving this vaccine to a pregnant woman? Are there lasting effects on reproductive health? I wonder if you could comment on that. Well, as you know, the vaccine is a sterile, self-reproduced. It's taken from the culture supernatant of a culture of anthrax. So there are no organisms in this vaccine. There's absolutely no reason to think that this would cause a problem in pregnancy. However, the risks associated with immunization during pregnancy are unknown because it hasn't been studied. And prudence dictates, therefore, that the vaccine should be deferred during pregnancy. While pregnancy testing is not indicated before vaccination, every woman of childbearing age should be questioned about the possibility of pregnancy. And if she may be pregnant, she should be referred for further evaluation before immunization continues. After she is no longer pregnant, if, in fact, she is pregnant, the vaccine series can continue where it left off. There's no reason to interrupt breastfeeding, either, as the vaccine can be given to lactating women. If there are any questions, certainly the woman should be referred to her primary care provider for consultation before continuing with the vaccine series. Well, thanks, Ed. Therefore, just to summarize for those of you out there in the audience, before immunizing any woman, you should ask her whether she could be pregnant. If there's any chance that she is pregnant and it's not already documented in her medical record, then she should be referred for a pregnancy test. If that test is negative, that female soldier should be vaccinated. If the test is positive, she should be deferred from immunization until completion of the pregnancy, as Colonel Eisen stated. And I want you to remember that all vaccines or virtually all vaccines that we use in clinical medicine today, including the anthrax vaccine, are labeled as pregnancy category C. And what this means is we don't have good information that proves that they're safe in humans. On the other hand, we don't have good information that shows that they're not safe. And in the case of the anthrax vaccine in particular, again, as Colonel Eisen alluded to, there's every reason to think this would be safe. But again, pregnant women should still be deferred from further immunization. So how is the vaccine given? Well, it's given subcutaneously at a dose of 0.5 MLs. And it's given at intervals of 0, 2, and 4 weeks, followed by doses at 6, 12, and 18 months. So it's a six shot primary series as shown on your screen. The zero dose is the day of the first vaccination. This initial series is then followed up by yearly boosters to maintain immunity. You know, just to summarize, this vaccine is certainly a wonderful step forward, we're far forward from where we were in biological defense a few years ago. But there's obviously some problems. And those problems are exacerbated by the fact that this is a somewhat unwieldy series of immunizations, six doses over 18 months. I know that's a problem for me. When I got the vaccine, it's a problem for me as a practitioner administering the vaccine. And I imagine it's a heck of a problem for the first sergeant who has to get his poor troop in there six times over a period of 18 months. And I think Colonel Opio probably wants to comment a little bit on that. Indeed, the largest challenge facing health affairs was to capture this all in an automated data system. This was an incredible task. The services had never, and to this date, have never done anything like this to capture 100% accurate all immunizations that are given worldwide. The task was sent out, and it was determined that the deer's data system would, in fact, be the central repository. And each of the services then developed their own interim systems to support this requirement. The Army developed the Med Pro system. The airports developed the Mets, the medical immunization tracking system. And the Navy developed the SAM system, which was already on board their ship, their shipboard automated medical systems. And so they're all feeding this data into a central data warehouse to capture all this data. And when you think about it, six shots over 18 months, who is in the same place at the same time? In the mobile force, we find ourselves soldier, sail, and airman always moving around. So we needed to be able to go into any medical treatment facility, regardless of color of service, and pick up that immunization with 100% accuracy. And the systems that the services have developed have allowed us to do that. An incredible task, and my hats off to the services for making that happen. The surgeon general as the executive agent in executing for the TSG rep, we try in the operations directorate to make sure that all these data bytes are in fact captured with 100% accuracy. We report on a weekly basis just the status of the force. And as you can see, this would in fact not be possible unless we had some mechanism for the commanders. And the commanders do in fact have that capability. There is obviously a manual system that goes along with all of this. We still use the SF-601, the medical record shot records that's placed in the records. That's a little yellow shot record? No, just a minute or so. That's the yellow one. I remember that one. That's the international, the VHS-731, that yellow shot record. So there's a redundancy in the systems. We still do the manual system, but we've added the automated tracking system to that as well. Being a former military brat, I remember that little yellow card. I would like to share though that the commander now has the responsibility of executing this program. I mean, we are providing the vaccine, we provide the plan for doing it, but it's actually a commander's responsibility. And so that commander has to have the tools available to him. And there have been some systems developed to do that. You should be able to dial up the DEERS address, www.dmdc.osd.mil.sicrs, and with those acronyms and get on, log on an ID. If you have a need to know, I mean, we don't want to sit on Hussain dialing up and giving access to it, but we do in fact want to have a reason for you to have access to that data bank. You can pull up by unit identification code or by social security number. Within the Army, we have developed the Med Pro system and we have put that on the web page. So if you have access to the worldwide web, you can dial up www.mods.asmr.com. And you know this is a .com, so it's available to anybody. And so there was some question about security and I'm sure the audience is wondering, well, can anybody do that since you brought up Saddam? What happens is when you put in your social security number, it is in fact traced back to the officer master file. And if your social doesn't register an officer master file or the enlisted master file, you don't get access to that system. So there's a security system, a secure layer that we've provided for that. I think it's just an exceptional system. From all the services and the deers as being the central repository, forbodes things to come with the centralized data management of all of our health data. But Colonel, what happens if you miss a dose? Well, if you miss a dose and you're within two years, you just continue right where we identify that missing dose. So up to two years for us, you can go ahead and continue on with your series. And under the new AVIP guidelines, this two year limit applies only to those personnel receiving a single dose. Personnel have received two or more doses can simply pick up right where they left off regardless of the delay between doses. Now, during Operation Desert Shield Desert Storm, 150,000 soldiers, sailors, airmen, and Marines were administered the anthrax vaccine. Most of these personnel received a single dose. And obviously, since it's been more than two years, those personnel would need to start over again. Those few soldiers who received two or more doses and who can in fact document the fact that they received two or more doses can again simply pick up right where they left off. Now, before we start on our next topic, we're going to check in and see if our studio audience has any questions and if they've been paying attention. Ted? What I want to do now is review some of the material we've covered up to now. We've got a long 12 hours ahead of us over the next three days and I think it would be helpful if we did a little bit of review. So I'll throw some questions out to our studio audience here. You've already heard a lot of talk about anthrax and certainly there seems to be a lot of emphasis both in this course and in the DOD in general about the use of anthrax as a weapon. And yet we see by this course that there are certainly many other weapons systems out there. So why the emphasis on anthrax? What about anthrax makes it such a fearsome weapon as compared to a lot of other infectious diseases? Anybody know? Sir, ma'am. As a spore, it's very easy to store, it's very easy to disperse and it makes an excellent biological weapon. That's right, good point. The point was as a spore, anthrax makes a good biological weapon. And in fact, that's a very important point. Most bacteria are not spore formers and those bacteria that aren't spore formers need the same things that you and I need in order to survive. They need food and water and love and affection and all that sort of stuff. But if I form a spore, I can go for prolonged periods of time without food and water. And consider how this makes the ordnance officer's job easier. If I'm an ordnance officer charged with storing biological weapons and I've got a plague weapon and a plague is not a spore forming organism. I've got to take the top off my warhead, fill it up with plague, screw the top back on, put the warhead in the bunker. Three days later, all the plague's dead. I've got to take the warhead out of the bunker, take the top off, dump the plague out, put new plague in, et cetera, et cetera. Well, with anthrax, I fill that warhead up with anthrax spores, put it in the bunker. 50 years later, that warhead is still viable. So I think that's just one of the many reasons anthrax is such a great weapon. Any other ideas? Dr. Knudsen. Another reason that it makes a good weapon is that it can be aerosolized in the one to five micron range and maintain its infectivity and stability in aerosol. Absolutely. It lends itself very well to aerosolization at exactly the right particle size. Being a spore, again, it can survive desiccation. You can dry it out. That makes it easier to disseminate via the winds, if you will, and just makes anthrax a better weapon in general. It tends to agglomerate in particle sizes of exactly one to five microns, which, as you saw earlier, are perfect for reaching the human lower respiratory tract. Any other reasons? Captain Nurgis. Sir, maybe military lore, but it seems everything I've been told, if you can make bread or beer at home, you can make anthrax. Absolutely. Absolutely. And again, we said earlier in the course that with two semesters of microbiology training, anybody can go outside their door, dig up a scoop full of dirt and readily culture some of these agents. An anthrax is an agent that's found readily in the soil. And again, the technology necessary to grow this stuff up in large amounts is not that complex. If you're a home brewer or a home winemaker, you certainly have the knowledge necessary to be a home anthrax brewer. So all of those very good answers indeed. Anything else? Anybody else want to add anything to that? It's an organism for which we have a vaccine, we can also treat it with antibiotics. So somebody who's working with it can protect themselves and goes around them. Right, and this brings up a critical point that we really haven't dwelled on a lot. The bioterrorist most of the time doesn't want to succumb to his experiment any more than we want to succumb to his experiment. So it's critical that he be able to protect himself. And with anthrax, he can certainly do that. He can vaccinate himself or start himself on antibiotic prophylaxis, safely work with this stuff and disseminate it. So that's a very, very good point. Well, let's move on to the next question. We've heard a little bit now about anthrax vaccine. And I wonder if anyone here could review for me some of the advantages or disadvantages of the anthrax vaccine. Any takers? Captain Bennett. Well, certainly one advantage might be that we do have a long experience with its use. It's been validated over a long number of years and used in a large number of people now. We have good experience with its safety and some good evidence of its efficacy. So we feel it's a fairly reliable vaccine. Great, great point. And I think there's the perception out there, even though we've covered this to some degree already in this course, I think there's the perception out there still that there's something experimental about this new anthrax vaccination policy. And in fact, nothing could be further from the truth. Anthrax was the first bacterial vaccine ever invented. So anthrax vaccination dates to 1881. The concept of anthrax vaccination is 117 years old. And the current anthrax vaccine was licensed in the early 1970s. It was actually available in IND form in this country in 1963. So we have been vaccinating veterinarians, veterinary techs, textile workers and slaughterhouse workers in this country for probably 35 years or so. So a very effective vaccine in that sense. Now I can't do the gold standard study. I can't give half of you anthrax vaccine and half of you placebo, blow anthrax into the room and see what happens for obvious ethical reasons. But according to a lot of monkey data, it certainly seems to be a very efficacious vaccine. And the anecdotal evidence would be exactly as Captain Bennett presented. We know that the amount of anthrax disease in veterinarians, textile workers and slaughterhouse workers has certainly diminished since the advent of anthrax vaccination. So that's one of the big advantages of the vaccine. Any disadvantages of this vaccine, Captain Nurgis? So I can talk about a disadvantage. When I was at Fort Bragg, we would have soldier readiness checks when we were getting ready to go anywhere. It's hard to get a battalion or a company or three or four people, especially doctors and nurses, down to the SRC to do it three times that on the vaccination schedule is a first sergeant's nightmare. Right, absolutely. And again, as I said earlier in the course, a problem for the patient, it's not pleasant getting six shots, a problem for the doc. It's a lot of time and effort and resources expended vaccinating or administering this many doses, vaccinating a big problem for the poor first sergeant who's got to get his troops in there. And I think, and this is just Ted C. Slack's personal opinion, but I think that if this were a more user-friendly vaccination, we probably wouldn't even be talking about it today. There wouldn't be this big to-do about the Department of Defense Vaccination Policy. We probably would have just done this decades ago. This would have been a no-brainer if it was a one or a two-dose series. Again, that's just my opinion, but any other advantages or disadvantages that anyone cares to comment on? It does have a degree of reactogenicity, so we do have some local reactions. Right, I have to deal with those. That's right, there is a little bit of a local reaction issue. It certainly doesn't seem to be much worse than with most vaccines. I can tell you from personal experience, I got six doses of this vaccine. It has a fairly high degree and there are a fairly high amount of formalin in it, so it stings a little bit for 20 or 30 seconds after it's been administered. Colonel Eitzen showed you that you get a subcutaneous nodule often that lasts for a few weeks after administration of vaccines. Painless, I can speak from experience. I got that after a couple of my doses and if I felt along my triceps, I would notice the nodule, but if I wasn't thinking about it, it certainly didn't come to my attention. So there are some local side effects. There's some redness and swelling in a certain minority of patients, but as you heard during the show, very few or almost no long-term or permanent side effects or serious side effects. Major Lee? Because it's not a live cell vaccine. It's a cell-free filtrate. You cannot get anthrax disease from the vaccination itself. Right, right. So very safe vaccine in the sense that there are no living organisms in the vaccine. This is unlike some vaccines, not a killed organism. It's just a cell-free filtrate. The vaccine is essentially pure protein and as such with theoretically as well as practically be assured of being pretty safe. Well, you've all done very well. It doesn't look like I'm going to stump you anymore with these questions. So I think rather than continue to try to do that, I will open the show up to the next agent that we're going to talk about, namely Plague. And to do so, I think I'll throw it back to Doris.