 Well, we're especially fortunate now to have one of the leading experts on smallpox and the person who was instrumental in the eradication efforts with us today. Dr. D. A. Henderson is now the director of the Center for Civilian Biodefense Studies at Johns Hopkins University. Welcome Dr. Henderson. Very happy to be here. The first one confused me last year since smallpox has been eradicated but I guess things aren't always as they seem. You're right Doris. You know, smallpox was eradicated by the World Health Organization. The last naturally occurring case of smallpox occurred in Somalia in 1977. In fact, smallpox represents probably the greatest public health success story in the history of public health. It is the first and heretofore only eradicated disease and we now this year celebrate the 21st anniversary of the global eradication of smallpox. In 1978 there was an additional laboratory case or two in Britain and in 1980 the World Health Organization formally declared smallpox eradicated. I wonder now if Dr. Henderson you could give us a description of that eradication campaign. Right, in 1966 the people at the World Health Assembly discussed the question of undertaking an eradication program and it was finally decided that we would and they allocated some 2.4 million dollars for the effort per year. The strategy as we began the program was twofold. One was to vaccinate 80% of the population in each of the endemic areas and the neighboring countries with the thought that this would markedly reduce the incidence of smallpox so that we would then be able to move on with our second phase of the program which would be reporting surveillance to find the cases and then containment. So that you would set up for each hospital and health center a reporting system so they would report every week whether they say smallpox or not and then there would be a team go out and if they had smallpox then they would vaccinate in that household and in the village and thereby stop the spread of smallpox because it spreads as a continual chain. Each individual is going to infect another individual and every two weeks you have a new case and every individual who develops smallpox has the typical disease. It's not like polio or other diseases we have many atypical cases. Every case is a person with rash and fever and all of the other symptoms. So it was very easy for us to identify a case and then contain it and stop the spread of these chains. Tenure target was set to complete the task. We missed the target by some 26, seven, eight months and 26 days. So at any rate the last case as you say occurred in 1977 in Somalia and since then there's been no smallpox anywhere in the world. Now as far as I've been led to believe there are two recognized repositories of smallpox or variole virus in the world that the Centers for Disease Control in this country and at the Institute for Virology and Biotechnology at Kultsovo in Russia. Is that your take on this? Well certainly from the World Health Organization when I was there and those who follow me we worked very hard to try to get the smallpox in as few places as possible so to be the least possible risk of spread of that virus getting loose again and really causing trouble. And I would say up until probably three four years ago we were pretty persuaded that this was the case. Now on the basis of people who've defected from Russia we understand there are probably two maybe three more sites in Russia. We also have the problem in Russia as we all know of chemists and physicists leaving the country to go elsewhere. Biologists have done the same. Are there possibly sites in other countries that may have the virus? We don't know but you can speculate. Well I'll tell you what at this point Ted why don't we talk more about the smallpox virus? Okay Doris the smallpox is caused by the variole virus and the variole virus was responsible for millions of deaths. One of the great diseases of antiquity again just like anthrax and plague. Responsible for again millions of deaths dating from before the 12th century BC as far as we know. The Egyptian pharaoh Ramses the fifth probably died from smallpox and that theory is based on examination of his mummified remains. After smallpox was introduced to the new world it's estimated that at least three and a half million Aztec Indians died of the smallpox. Well in fact Ted I think it's been even more severe a problem to the Indians than that and many people don't realize this but as we've gotten back in the history we began to realize that the death rates among Indians may have been as high as 75 to 90 percent. A really remarkable number of deaths and we have many accounts of whole Indian tribes being wiped out within a period of really a couple of years. There were so few people left that they couldn't sustain themselves and they died out. So that in fact when the pilgrims landed in North America they had very little difficulty with the Indians but what's not talked about is the fact that this was only two years after a major epidemic wiped out huge numbers of Indians along the eastern seaboard and permitting the pilgrims to settle peacefully. You know Doris I think there's the perception out there amongst a lot of people still that biological warfare is something very new product of a brave new evil world if you will and I think we showed yesterday that in fact that's far from the truth in 1346 against again the plague was used against Kafa. Well I'm here to tell you that unfortunately even in the United States biological warfare is nothing new it dates back a couple of hundred years. During the French and Indian wars Sir Jeffrey Amherst of the British army was tasked with capturing Fort Carillion now known as Fort Ticonderoga from its Indian defenders and he hit upon the idea of taking these scabs of smallpox victims grinding these scabs up and placing that infectious powder into blankets and then passing the blankets off as gifts to the Indians and in fact this unfortunately worked as well the Indian defenders of Ticonderoga succumbed to the smallpox. Isn't this what you call the gift that keeps on giving? That's right, the gift that keeps on giving. Right and Dr. Henderson I think probably can tell us some more terrifying stories concerning smallpox you may have learned from Dr. Alabak. Right I think from that time of the French and Indian wars until now we've until very recently certainly there's been no thought or threat of smallpox being used in this way in fact in a large part I think it's because we've had so much vaccine that's been available and people have been vaccinated around the world but Ken Alabak who was the number two man in the Russian bio weapons production setup tells us an interesting story that in 1980 just as we decided as the World Health Assembly pronounced that smallpox had been eradicated and advised that everyone stopped now for vaccinating which they did. They saw this in the Soviet Union as an opportunity and with this they developed a very large production plant for smallpox virus as he tells me the plant one plant has a capacity of producing 100 tons of smallpox virus per year and this is still extant developed since 1980 and a large scale production facility so this is something that is really very much of concern at this point in time with all of the troubles in Russia right now. Well smallpox I guess can be an even greater threat than some of the other agents because it can be transmitted person to person correct? Yes it can and I think the two major diseases which can be transmitted to person to person are plague and smallpox but actually smallpox is much easier to transmit than plague and so I think in my judgment I would rate smallpox right at the very top of the list as the most severe most serious of the problems that we face. You know Doris I just want to re-emphasize something we said yesterday from a military perspective one of the main tenets that a battlefield commander wants to adhere to is to maintain control of the battlefield so a disease such as smallpox if a commander unleashes that disease it does its dirty work but then it affects the civilian population and continues to propagate and the battlefield commander in essence loses control of the battlefield from so from the perspective of a military weapon perhaps smallpox isn't quite as attractive but to the terrorist who doesn't care what he unleashes on humanity this may be in some sense the ideal weapons. Right how does the virus cause the disease? Well following an asymptomatic incubation period of about 12 days actually ranges from seven to 17 days but you can almost set your watch by this 12-day average. Following that 12 days there's then an infection that develops in the respiratory mucosa proliferating virus particles circulate around the lymphatic system to the regional lymphatics from there a minor viremia ensues and virus spreads to the liver the spleen the lungs the bone marrow once that happens the prodromal symptomatology starts you get two to three days worth of fever nausea malaise the I don't feel goods during that time a major viremia ensues seeds the skin and following that the characteristic exanthem that most of us would know smallpox by develops. Okay well as well as Dr. Henderson Dr. Don Hopkins a former deputy director at the CDC was also someone closely involved with the smallpox eradication efforts in the 70s in India and Sierra Leone. So let's listen to him describe cases of smallpox that he treated. 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 this 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 felt generally flu like symptoms felt miserable already a virial a major this 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 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 to to to descovate internally sometimes people would be losing the entire lining of their bowel or having fluids to ooze into their into their lungs sometimes the virus would attract would attack vital places such as the heart directly for example and as infection wore on sometimes people get secondary infections of the open wounds on 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 it was also a peculiar stench associated with all of this decaying flesh on a living on a living person and so to go into a village where you had several people like this and other villages terrified some of them unimmunized was a very it 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 have progressed to the state of already having the rash you know Doris as a pediatrician i think you could see it would be easy to confuse this disease initially with chickenpox and in fact that's the primary disease in the differential diagnosis of smallpox not too many other things that would look like this so initially on the first day or two or maybe three of the xanthum it would certainly be very easy to confuse it i think would be easy to confuse a case of smallpox with a case of chickenpox once the disease progresses though and you get to the point you saw in some of these pictures i think you could see it's pretty easy this is a no brainer diagnosis essentially and i guarantee that after you've seen a case or two you'll never forget it won't be too tough to make the diagnosis thereafter um ted i think you're absolutely right on that and uh i'd say 90 percent of the cases turn out to be very typical but not at the beginning it gets to be a little bit difficult right at the beginning and i think perhaps we can see a succession of pictures here which may portray this the individual once he was infected with the disease would have a very high fever i would feel aching pains in the back and uh and headache he'd have nausea may be vomiting may even have enough of intestinal pain that he might look like an acute abdomen and this goes for two to four days normally and the individual usually goes to bed he's feeling really rather miserable then the rash begins now we have here we have day two you just see uh small macular vascular macular lesions coming up and we go on to look at subsequent days you'll see this is the same child day by day this is i should note at what we call an ordinary case of smallpox it's not a serious case day four you can see it's becoming a little more apparent and you will note that the the lesions if you look at those on the face you'll see them all at the same stage of development they're all kind of pustular if that were the case of chickenpox you would see scabs and pustules and little macules all in the same area but here you see all those lesions are the same now we're up to day seven we move on to uh what do we have day nine next day eight and at this point the patient is feeling very miserable indeed and uh he has the most of the lesions are going to be on the face on the arms on the legs there will be some on the trunk but not as many and we call that a centrifugal distribution uh it's in contrast to chickenpox in which there are more lesions on the trunk and many fewer on the face arms and legs why this is so we have no idea we go on to the next uh slide now this shows foot and hand now you'll see the pustules on the palms of the hand there and similarly in the soles of the foot uh this is also classically smallpox you'd rarely see those lesions in chickenpox on the palms and soles now let us move on to the next uh well now you see scabs are beginning to form uh and uh some of them you'll see on the upper chest they're beginning to fall off they leave depigmented areas for a period of time we go on to the next now we're up to day 20 now most of the scabs are separated and the individual will have on the on the face wherever one of those pustules is present there will be a scar so that the individual will be really quite extensively scarred so as we think about it the difference between smallpox and chickenpox and chickenpox is the one disease that really was confused most often with smallpox with chickenpox you have the centrifugal smallpox the centrifugal uh distribution and in chickenpox centripetal you have the lesions appearing in the any one area are all the same with smallpox and thirdly you will see them on the palms and soles and with that you shouldn't have any difficulty in diagnosing it this is a truly horrible disease i mean does everybody have the same type of symptoms well Doris as uh Dr. Henderson alluded to about 90 percent of patients would be expected to develop what you just saw here variala major there are variants of the disease however um again that child you saw was variala major but variala minor uh and i think we have a slide of that uh this woman here this ethiopian woman you can see doesn't really look that sick and in fact she's still able to get out and about go about her daily chores take care of her family despite having this variala minor disease variala minor features milder systemic toxicity smaller pox lesions it has a much lower mortality rate one percent in unvaccinated victims versus the 20 to 40 percent that we would have seen with variala major but ted what determines whether you get major or minor well uh i think dr. Henderson might be better able to talk about that probably strain differences amongst viral strains there were two major two differences two types of virus one was a variala major which caused the severe disease and that's what we saw throughout all of asia and a lot of africa the other disease with variala minor which only caused one percent death rate and we saw that in ethiopia we saw it in southern africa and we saw it in latin america so that i think if we were worried about this as a bioterrorist agent we would be looking at variala major as being the one that would be used i don't know if you wanted to say anything about any of the other variants uh flat type smallpox hemorrhagic smallpox right i think in dr. hopkins pictures there were a couple of patients that had the hemorrhagic form these are particularly of concern the individual comes down with this sort of disease with all the hemorrhaging and it's very atypical there's no real rash as such and so that uh you're very apt to miss this diagnosis entirely when we've had these cases admitted to hospital they are uh pose a special problem because they excrete a lot of virus they expose patients they expose staff and in a bioterrorist attack these are cases that are likely to get into the hospital before the diagnosis is made because they have a shorter incubation period as well so the ones the hemorrhagic cases and what we call the flat cases which the skin just sort of forms a velvety kind of swollen texture are very difficult to a diagnosis indeed well it seems the clinical picture is very diagnostic of smallpox is there any other way to diagnose the disease well in the laboratory i think the very straightforward way to get a diagnosis very quickly and that's to take a little of the postulate fluid or a little material from a scab and you put it under the microscope an electron microscope and you will see a picture there it is of this very characteristic kind of brick shaped organism now you can't tell whether that is smallpox or vaccine vaccine the vaccine virus or cowpox or monkeypox but if you're seeing that patient as sick as that you know it isn't cowpox you know it isn't vaccine and unless you're in africa it's not going to be monkeypox so that's smallpox okay now smallpox is contagious does that mean that anyone who comes in contact with a smallpox patient will get the disease well doris when smallpox roamed the earth about 30 of non-immune people who came in close contact with a victim would be expected to develop the disease that incidence would increase in places with a low relative humidity as was seen in parts of africa where this disease held on the longest i guess it's difficult though in the individual case to decide who's going to become infected and who isn't and dr hopkins i think has had extensive experience with exactly that question okay well why don't we take another look at dr hopkins describing his experience with the infectivity of smallpox in uh in in some instances you you really couldn't predict this virus i recall uh very much an instance in which we had an explosion of smallpox around a prominent man who had died of smallpox both of his wives had been infected and in fact one of them gave birth just before her rash appeared when i arrived in the village this baby had lain on the floor of this mud hut between the mother and the mother's co-wife both of whom had severe smallpox rashes the baby was about a week old and had not been infected i vaccinated that baby that day and came back a week later to see a very nice vaccination scar and i visited that village several times the baby survived i still uh do not know or understand why that child was not infected because in fact pregnancy put women at much greater risk of dying of smallpox and the fetus was also at risk because under those circumstances suppressed immunity the fetus and the mother often got severe smallpox and would die but that child at the best one could tell didn't even get uh infected in other instances there were situations where people did not even know they had been exposed to smallpox they either had encountered somebody who was in the prodrome and didn't yet have a rash or they simply didn't know that somebody had a rash they didn't didn't notice but one of the advantages about this disease was that people who were infected to others generally unless they were in in the in stages of the incubation disease they had a rash and not only that they had a rash on their face so you generally wouldn't know it but sometimes every now and then when we encounter people who didn't know how they had been infected or or by whom and in in those instances it was airborne from somebody uh that they didn't they didn't even see the rash well once you've been exposed is there anything you can do to prevent the disease from occurring well i think you can prevent the disease if you're vaccinated beforehand and it would appear that if one were to vaccinate someone within say the first three four five days you might prevent death from the disease now at one time we had uh vaccination was worldwide and in this country every child was required to have vaccine by school entry so that we were a very well vaccinated population but most of the rest of the world was too then in 1980 with the declaration that eradication had been achieved the decision was made to stop vaccination it was a wise move because the vaccine is not without some risk now we've had no vaccine used in the u.s for probably 25 years so we have a very large susceptible population as far as vaccine is concerned we now have probably enough to vaccinate five six seven million people in storage at this point in time but we have no vaccine manufacturing capacity anymore in this country and indeed we don't have any in the rest of the world so that is the much vaccine as we have right at the moment something we're going to have to be very careful about using do members of the military still get vaccinated well Doris uh the general public stopped getting vaccinated in 1972 in this country for a while after that the military continued to vaccinate then they stopped a few units started up again there were some minor service specific differences but basically sometime in the 80s the military stopped vaccinating as well and i think it's safe to say that probably virtually no one under the age of 25 right now in the united states has been vaccinated well i'm just slightly over the age of that and i was lucky enough to get vaccinated as a child so i'm safe right right well i wish i could say yes but we now we know that the vaccine given once is not going to be fully protective and it was learned very early that revaccination was going to be necessary so i'm not sure that you or anybody else at this point who's vaccinated 25 years ago is going to be protected against the disease Dr. Harrison you know i was vaccinated in childhood if god forbid i ever came in contact with smallpox could i at least expect to get a milder case of disease i think some of the people would get a somewhat milder case and might not excuse me might not die as a result of the infection which would be i think fairly important but uh indeed after 25 years we have the feeling it's not going to be a lot of protection that you will have we're in the same boat together all right now if i get exposed to smallpox and i've never been immunized or it's been a long time what do i do next well Doris one of the first things you should consider is to get vaccinated again the vaccine is licensed it's very effective that's not to say that civilian practitioners would have access to it necessarily but in a national emergency like a smallpox exposure hopefully we would be able to procure vaccine and give to you so you'd want to consider getting vaccinated the vaccine is effective we know that from the eradication campaign in africa it's administered by intradermal inoculation with a bifurcated needle a process that became known as scarification because of the permanent scar that resulted in in fact we believe that if you didn't get a scar you didn't have an adequate vaccine take so that thing that's right there on the arm that's it right that's it the scabbing and the scarring show that you have had a good clinical take so for a while at least in the past you were protected if you didn't have that again that's an indication that the vaccine you had been given might not have been effective if you get revaccinated however you might not develop a scar the second time around you usually do develop a vesicle five to seven days post inoculation you get some surrounding erythema and induration of that vesicle lesion forms it scabs over and it gradually heals over the next one to two weeks that would be the way we would normally expect it to play out now dr Henderson you said the vaccine is not without some risk what are some of the other side effects beside the scarring well there's several not let me mention those and for just a moment but i think it'd be useful to look at a picture of a normal vaccination because it's very few people have seen this in this day and age and it you can see it looks somewhat ugly there's this postular lesion in the center you'll see some erythema around there it's redness out there for quite a distance the individual may have some fever he may have some lymph adenopathy associated with this and this is just a normal reaction i think there are many who look at that and say well there might maybe there's some bacterial infection there and maybe we ought to do something about it but in fact this is not bacterial super infection this is just the normal reaction that one may have now if we can see a couple of other reactions uh i think we have some that we can show here here you see a number of lesions around the main lesion that may come about as a result of the individual scratching the lesion and spreading it around that area when you get that kind of spread there's nothing to worry about in fact all each of these lesions will basically go through an evolution as though they'd all been inoculated at the same time so it's not a big problem however you can spread it to other sites and they can be a problem and here you see a woman who has rubbed her eye after having been inoculated and she has a vaccinal infection of the eyelid now that shouldn't be a problem but if it gets onto the cornea it can be very serious and and that is not so good we go on to another one here now here is a situation with a child i think this is a childhood leukemia and people who have a vaccine or immune deficiency disorder may have this very severe form of a vaccine in which the organism keeps growing and it's called vaccineinacrosum and this can often be fatal and this is quite a serious matter to have that for a vaccineinacrosum you can use vaccineinimmune globulin to treat it but it's not a pleasant disease are there certain people who shouldn't be vaccinated well doris as dr hinderson alluded to there is a condition called that eczema of vaccinatum and that can occur in people who have eczema and i think we have a picture of that eczema is a significant dermatologic disease in many patients and eczema vaccinatum is a horrible condition that is associated in cases with mortality and so eczema was a relative contraindication to vaccination i should point out though that you know if you were truly exposed to smallpox smallpox a very deadly disease and you might still consider immunizing or alternatively giving vaccineinimmune globulin to those patients one of the worst side effects was seen in immunocompromised individuals and we just saw the picture of a belukemic child who was inadvertently vaccinated in this day and age with the advent of modern intensive care bone marrow transplantation and the hiv epidemic we see far more immunocompromised patients than we ever did before and people with hiv or these severe forms of immunosuppression probably should not be vaccinated even if they get exposed to smallpox and that's going to be a judgment call but the alternative for an hiv patient for example would be to just give them vaccineinimmune globulin instead of immunization there's an issue though with pregnant women and i believe we have a picture of a fetus who died of fetal vaccinia when his mother was vaccinated during the days of smallpox immunization now this brings up a kind of a tough conundrum for us again smallpox a very deadly disease smallpox deadly to the fetus if the mother gets smallpox as well and so pregnancy is not an absolute contra indication of vaccination if you get exposed to bona fide smallpox and you're pregnant you probably should still be vaccinated this really isn't that common a condition but it's a condition clinicians should be aware of. Well Dr. Henderson and it sounds like the vaccine can be kind of dangerous to use. Yes i think in showing these pictures i think this is emphasized too much the reactions to the vaccine when in fact serious reactions to the vaccine were not all that common uh one in five hundred thousand was the number that would have a serious reaction it isn't to say that they wouldn't have some lesions on another part of the body that was not serious but serious reactions one in five hundred thousand and that's not a very high number we'd like to have none but no vaccine is totally safe every vaccine we have protects and you you want that protection it also has some risk and you're weighing benefit and risk all the time as one looks at it i think Ted as you've said uh if you're faced with a situation where you're exposed to smallpox uh what contra indications are there and i know uh during the global program and smallpox eradication we considered this very carefully and we finally said you know smallpox is so dangerous compared to vaccination that the only contra indication that would would be appropriate would be that if the individual looked like he might die the following day then you won't vaccinate him because he might be wrongly blame the vaccination for the death so that i think uh this is i think puts it into perspective is to just how important the vaccination is under the times of terms of a threat okay what is vaccinia immune globulin well Doris uh vaccinia immune globulin or VIG is a way to provide passive immunity to people exposed to viriala but i want to emphasize that VIG is really designed to treat the complications of vaccination more than it is to be a treatment for viriala the u.s army maintains a modest supply of vaccinia immune globulin and it can be used for those eczema patients and pregnant women and severely immunocompromised patients what about public health measures i mean wouldn't cases of smallpox be an emergency situation uh we always regard smallpox as an absolute international emergency because if smallpox really is out in the community the potential for spread across the world is there and so that to regard this as an absolute emergency is key now just how uh smallpox might spread and the potential of smallpox as an aerosol became apparent to us in 1970 and that year there was a an electrician a german electrician working in pakistan who came back to a town of machete in germany uh he had some diarrhea he had a fever they thought he had typhoid fever and so they decided to isolate them they isolated him in one room of the hospital and were able to verify that in fact there were only two nursing sisters who saw that patient they vaccinated everybody in the hospital or gave them vaccine immune globulin they vaccinated a hundred thousand people in the in the town they uh they quarantined the hospital so nobody would leave and what happened well let us see the next picture i think this is the this is the picture actually of the german electrician now he developed smallpox three days after he was admitted into the hospital he was immediately evacuated to a german smallpox hospital yes they had special smallpox hospitals in germany and in britain which were kept fully uh equipped to be opened only if smallpox was introduced into the countries i think it's an illustration of how much the country's worried about smallpox so he was only in that hospital a very short time now what happened can we see the next slide here you see the green that three days or four days where he exposed possibly could have exposed others and you see this big wave of cases of some i think it's 17 cases that occurred and those cases occurred in rooms adjacent to his they occurred in rooms on the second floor of the hospital he was on the ground floor there were some of those cases which occurred on the third floor of the hospital there was one case in a visitor who had can't come to the door of a long corridor opened it way the patient's room was way at the other end opened the door asked for directions closed it again and uh 11 days later he had smallpox now what was what was strange about this what was strange was that the patient had cough and with smallpox we rarely saw cough uh we suspect he may have had a complicating influence at the time and there's nothing that's going to produce an aerosol quite so effectively as cough so that we figure figure in this case that this was an aerosol of smallpox which covered three floors of a hospital spread from that patient and i think it illustrates i had what the potential of smallpox in an aerosol to spread to infect to really cause a lot of trouble and bear in mind those people in the hospital most all of them had already been vaccinated in childhood and now they're older and they came down with the disease and some died so there is some real cause to be concerned with an individual in that situation this is a scary disease right you know Doris i think every parent out there is familiar with the fact that if your child has chickenpox and their lesions become scabbed over it's safe to go back to daycare back to school or wherever it's important to remember though that in the case of smallpox patients are infectious to others from the time of onset of the xanthum until the scars are completely or the scabs are completely healed until the scabs have fallen off if you will so very different in that sense from chickenpox infectivity as dr. Henderson stated is enhanced in the presence of a cough contamination via contaminated bedding or other fomites really is not an important way of transmission only occurs fairly infrequently okay is there anything else we need to know about decontamination well just that all objects in contact with the patient the linens the clothing the ambulance and its surfaces etc require disinfection and that would best be accomplished by sodium hypochloride solution by steam or by fire the regular decon of soldiers after exposure to an aerosol remains the same as it would be for most other agents bleach or soap and water as a field expedient if you don't know that personnel have been exposed until after the first patients arrive it's been long enough by then in fact 12-day incubation periods been more than long enough so that decon of the unit at that point wouldn't accomplish anything you need to remember again the incubation period for smallpox is much longer than with many of the agents we talked about yesterday for example okay is there a treatment for patients who have the disease well Doris besides supportive care there's really no specific treatment at this time you sam red is working on some new pox viral therapeutics now and there have been some good results seen with a specific antiviral drug a sedofavir all right Dr. John Huggins from you sam red is the primary researcher on the side of side of a fear sedofavir thank you trials let's hear from him what his preliminary results are when we recognize that smallpox was perhaps a disease that we were not quite as ready for as we ought to be we ask ourselves what were the vulnerabilities and clearly therapy for smallpox was a vulnerability that the u.s. had and so we ask a question what potential therapies would there be for that and one of the things that we noticed is that the the enzyme that replicates smallpox is essentially the same enzyme that replicates herpes viruses and because of that a whole class of drugs developed against the various herpes viruses had a potential to work against smallpox so we went to the cdc and tested these drugs against smallpox and found that side of a fear a class of compounds are licensed for cmv retinitis also inhibited smallpox virus is difficult to work with and particularly do animal studies but also monkeypox and cowpox and other viruses that we have animal models that we could really test a drug to see if it would work and using those models we've been able to determine that in fact side of a fear does work and we're continuing to aerosol infect animals to simulate a smallpox infection and we can in fact treat those animals we're trying to determine at the moment how late an infection we can treat but it looks very encouraging for us certainly in the incubation period it looks like that it's going to be very effective we can prophylax animals that we're going to infect and we can treat animals at the moment 24 hours after we infect them and whereas the control animals develop a bronchodemonia much like patients with monkeypox do and like smallpox fatal smallpox cases do a control animal will develop fatal bronchodemonia and die with say pulse oximetry values down around 50 whereas the drug-treated animals never fall below 90 and are essentially asymptomatic during the entire treatment period so it looks like we've got more work to do but it does look like this drug has good good potential to work against smallpox I think that clearly since smallpox has been there is no naturally occurring smallpox we're never going to be able to do the classical two drug efficacy trials that the FDA normally requires we are going to where monkeypox exists and it has become a reemerging disease in the the old Zaire and we're going to look to see if in fact there are enough cases there that we can do a clinical trial but like a lot of other biowarfare agents we're probably never going to know truly that it works against smallpox until we actually have to use the drug luckily there is very little difference between smallpox and monkeypox both in the virus and in the way that say monkeypox infects monkeys so I think we've got very good surrogate models and we can treat monkeys and we can measure the same things that a normal patient would would measure so I think we're going to come very close although we're clearly never going to know that it works against smallpox until there's actually a biological incident. Doris I just want to clarify something for the studio audience you know Dr. Huggins works at USAMRAID and I bet there are people out there saying hey I thought there's only smallpox at CDC and at Colts Ova how's this guy working with smallpox just wanted to reassure people that he did that smallpox research at the CDC and not at USAMRAID all right well Dr. Hidderson I think we ought to now I think this drug that he's talking about certainly sounds pretty promising to me I don't know if you have any take on that yeah I think as we've looked at it it does look very promising but I think from the stage where it is now so it's actual use in humans there's a lot of work to be done yet and I don't think we we want to be too optimistic too early because we don't have very much of the drug there's a lot of testing to be done yet all right well we'd like to thank you very much for being with us thank you and now it's time to move on to Venezuelan equine encephalitis or V and we'll be right back with our next guest