Monkeypox Explained Clearly

we're going to talk today about monkey pox as there's been some more information coming out about the most recent outbreak in 10 countries worldwide with over 127 people infected that have been confirmed monkey pox is a dna virus that is in the ortho pox virus family it's actually related to smallpox but not as dangerous so some key differences to know is that first of all it is a dna virus and whereas with sars cov2 which had 30 000 rna codes basically the monkey pox is a double stranded dna virus and it's much larger it has 200 000 base pairs so much larger virus so probably more pairs to sequence and probably more genes to sequence as well it's probably been infecting humans for a very very long time but it was first isolated in 1958 in crab eating the cox these are like monkeys and that's where the name monkey pox kind of stuck now it made its jump into humans at least that we could see in the democratic republic of congo in the 1970s that's the central african republic and as you can see here from this webpage which we'll put a link in in the description below the democratic republic of congo is where this was first discovered and this is where we see the central african strain of the monkey pox virus now there is a west african strain which you can see here in these other countries in west africa and that's important to understand because the death rates from infection from the central african strain is ten percent whereas the west african strain is about one to three percent and at least early on now as we're looking at these viral infections in the uk the united states they seem to be related more to the west african strain the other thing that's really important to understand is that even though it has the word monkey in the name monkey pox it's kind of a misnomer because actually these types of infections come from any small african mammals and rodents and that was highlighted with the recent outbreak about 20 years ago in the united states and let's talk about that and that'll set the stage for where we are right now so back in january of 2004 there was a paper that was published in the lancet infectious diseases titled human monkey pox and emerging zoonosis and zoonosis is simply a disease that comes from animals and let's read this abstract here because i think it's really interesting human monkey pox it says here is a rare viral zoonosis endemic to central and western africa that has recently emerged in the united states of course this was published about 20 years ago laboratory diagnosis is important because the virus can cause disease that is clinically indistinguishable from other pox-like illnesses particularly smallpox and chickenpox although the natural animal reservoir of the monkey pox virus is unknown rodents are the probable source of its introduction into the usa a clear understanding of the virulence and transmissibility of human monkey pox has been limited by inconsistencies in epidemiological investigations monkey pox is the most important ortho pox virus infection in human beings since the eradication of smallpox in the 1970s we'll pause there understand that the eradication of smallpox in the 1970s was mostly in part due to vaccines and as you'll see later it was those vaccines that also had an import in reduction of monkey pox let's go on there is currently no proven treatment for human monkey pox and questions about its potential as an agent of bioterrorism persist so the good news is is that scientists have been looking at this particular virus for some time and they've understood quite a bit about it this is unlike what happened two years ago when we were looking at the brand new virus of sars kovi ii also interesting here is that there was the specter raised of this virus being used as bioterrorism so we'll get into the symptoms in a little bit but i wanted to take you back to the year 2003 because it was this year that there was an outbreak in the united states of monkey pox and this was because of animals that were transported from endemic region of central africa that was transported and was brought into the united states and caused animal to human infections and there was a study that was done looking at those of the ones that had medical records 34 of them were researched and they were found in almost every case to have a rash that progressed to a raised lesion that progressed to a pustular lesion a we'll show some pictures of later and that lasted and crusted over and took about two to three weeks for that to completely go away this would show up on the trunk of the body that's a central portion then go to the arms even the palms and soles and then crossed over after a long period of time there was further investigation done during thi time to see just how far this infection had gone and what was interesting is that they had picked up on a number of people in this case particularly three individuals that were positive for the antibodies against monkey pox but never knew that they had symptoms and what it came out was is that they had actually been vaccinated against smallpox and get these years here this is really interesting one of them was 13 years prior another one was 29 years prior to the infection with the monkey pox and another individual 48 years prior was vaccinated with smallpox vaccine and that seemed to confer protection against symptomatic monkey pox disease so as you can see this is going to be an important discussion when we talk about treatment and prevention here at the end but let's talk about what are the symptoms of monkey pox and what you would do to look for those so when they looked at the outbreak in 2003 in the united states they noticed that those that had the monkey pox virus had a rash 97 of the time fever 85 of the time chills 71 percent of the time in large lymph nodes 71 of the time headaches 65 of the time and muscle aches 56 of the time and here you can see what the progression of the skin lesions look like as posted here by the uk health security agency early on this is about a three millimeter diameter vesicle it looks like it's fluid filled it's raised here it turns into a small pustule about two millimeters in diameter you can see here this is an umbilicated which means it looks like there is a umbilicus in the center of it this is a pustule about three to four millimeters in diameter here it's ulcerated where the actual lesion has gone down in the center it's about five millimeters in diameter here we have some encrusting of a mature lesion and then finally here what we call a descrimitive reaction where the skin comes off the top and it's partially removed scab so this is the type of lesions that we would see and there would be multiple of these okay let's talk about how this virus gets transmitted now and classically there are two ways that this can be transmitted there it's through humans and through animals and of course close contact touching sores especially if they're open or even touching the clothes that the patient was wearing and picking it up from there in terms of animals it would be much of the same so close contact but also biting and scratching or even eating the meat of those animals and we're talking about small animals like rodents prairie dogs things of that nature now in terms of incubation that's another issue and it may depend on the mode of transmission for instance it would be shorter incubation period if it was something like scratching or biting and it's been said up to nine days so for biting and scratching nine day incubation period before you would start to actually see this that's quite a long period of time the touching however can be up to 13 days even longer now classically the r naught that we've been talking about for some time in terms of transmission from coronavirus can be above one or two generally speaking for monkey pox it's somewhere between zero and one which means that these outbreaks tend to fizzle out because the person can not always reliably transmit this virus because it's obvious when the person has the virus and it's easy to isolate these patients what's notable here and that you should understand is that large respiratory droplets have also been implicated in the transmission from human to human of monkey pox and specifically it's not like it would be with measles or even sars kovi 2 but for instance if you are within six feet of somebody you would have to be there for at least three plus hours to have reliable transmission this is classically what is being noticed this is classically what is being observed what's different now is we're starting to see more and more patients becoming infected an specifically in a population in the uk that is a population of men having sex with men but that's not all there was also a report of a sauna outbreak of monkey pox let's take a look at those reports at this point as you can see here in this article that we'll put a link to in the description below the majority of the uk cases have been detected in gay and bisexual men leading the uk health security agency to advise gay and bisexual men to be aware of any unusual rashes or lesions but in this article that we'll put a link to in spain it seems as though most of the cases there in spain were linked to a sauna it says here that monkey pox cases in spain have been linked to a super spreader event at an adult sauna in madrid britain's monkey pox tally now stands at 20 after 11 fresh cases were announced on friday and contact tracing and quarantine of close contacts is underway enrique ruiz escudero the region's cabinet minister for health of the community said on friday that health officials had traced many of spain's 30 monkey pox cases to a single sauna in the capital while in belgium three cases have been linked to a large scale fetish festival in antwerp according to organizers also in the article it reported that in the uk a link was first drawn between gay men and monkey pox earlier in the week with the uk health security agency urging men who have sex with men to be alert for any new rashes or lesions on their body including their genitalia and you can see in the article here a nice picture of what these pustules look like and what cells infected with the virus look like as well okay let's talk about treatment so generally speaking the treatment for monkey pox is really supportive care that means if there's nausea and vomiting you make sure that they are well hydrated and don't become dehydrated you make sure that their electrolytes are replaced and if this is done most people recover that being said there are antiviral treatments the first one is ticovarimat 600 milligrams orally twice daily generally speaking for 14 days now this is fda approved for smallpox and it was fda approved in july of 2018. so this would be considered off label for monkey pox but it seems to work very well in both situations and the mechanism of this drug is that it prevents the formation of a very important protein in the virus that makes it infectious and able to infect other cells in the patient the next antiviral medication brings the dopaminer at 200 milligrams orally weekly times two doses this was fda approved for smallpox as well this one was in june of 2021 the last one is sidofover but the issue with this one is is that it's not really approved for smallpox or even monkey pox but rather cmv retinitis and the problem with it it can cause problems with the kidneys in fact there's a black box warning on that one so be cognizant of that now the thing you should also know is that you can't really get these medications from pharmacists because the drug companies will only distribute this to the us department of defense and or the cdc and so these medicines are going to be coordinated with any particular smallpox outbreak or in this case monkey pox outbreaks so let's talk about vaccines for monkey pox and to do that you're going to have to understand a little bit about the history of vaccines in terms of monkey pox over the last decade or so so one of the things that you're going to have to understand is acam 2000 and genios so these are the two vaccines that have been on center stage for the last two decades a cam 2000 was a vaccine that was approved in 2007 and it was at its core a replication competent vaccinia virus which means that it actually did replicate inside of the human cells where the vaccine was given and it caused what they call here a take so you knew that the virus had taken hold and it was to create the antibodies that were necessary for the patient who took the vaccine to get the appropriate antibodies to protect them from monkey pox and also smallpox however because it was replication competent in other words it could replicate there were risks of inadvertent inoculations and auto inoculation there were risks of serious adverse events particularly myoperacarditis in 5.7 per 1000 primary vaccinees now the effectiveness of this was good compared to the one that was prior to this in 2007 which was drivax that was the standard prior to 2007 which is when acam 2000 was fda approved and the way that this was administered was in the skin by multiple puncture techniques in a single dose in september of 2019 there was approved genios now this is also a vaccinia vaccine specifically it's a replication deficient modified vaccinia and cara and what that means is simply that the vaccine contains a virus that does not replicate and so because it does not replicate that reduces the risk of a lot of the side effects that they saw with a cam 2000 so there is no quote take after the vaccination you don't see a lesion in the area where the vaccination was given there's no risk therefore of inadvertent inoculation and auto inoculation they expect there to be fewer adverse serious events with this replication deficient modified vaccinia and cara and the cardiac adverse events are believed to be lower than that of the previous vaccine which was the acam2000 and the way that this is administered as you can see here is subcutaneously in two doses 28 days apart and i'm taking this from a screenshot from a cdc presentation which i'll put a link to which was over an hour long and spoke specifically into the particulars of these two vaccines now if you're wondering how they came up with the efficacy for the new non-replicating vaccine genios they say here in this fda news release about how they did that and because there was already a gold standard vaccine they weren't going to do a randomized placebo-controlled trial because that would be unethical to give anybody a placebo to see if that was going to work and so what they did was something called a non-inferiority study where they gave half of the participants the old vaccine and half the new vaccine and in this case they looked at the immune response in both and they were found to say quote the group vaccinated with genios had an immune response that was not inferior to the immune response to acam 2000 they also say that vaccine effectiveness for the prevention of smallpox was also inferred from supportive animal studies that showed prior vaccination with genios protected non-human primates who are exposed to viruses related to the smallpox virus and of course there's more to the story than just effectiveness we also want to know about safety and this is the statement the safety of genios was assessed in more than 7 800 individuals who received at least one dose of the vaccine the most commonly reported side effects were pain redness swelling itching firmness at the injection site muscle pain headache and fatigue no safety concerns would require a medication guide that have been identified virginios and genius is administered in two doses given four weeks apart okay so what happens if you think you've been exposed what is it that you could potentially do after you've been exposed to the virus to prevent it from actually causing disease well the first thing that you can do is actually get something called vaccinia immunoglobulin and this is what people who are immunocompromised might need to do basically these are antibodies that are derived from either patients who have had the infection in the past or they are genetically engineered to be antibodies against vaccinia which will cross react and also go against the monkey pox virus however the cdc recommends even up to 14 days post exposure you can actually take the vaccine but generally that is for immunocompetent patients and as you can imagine because of the effectiveness of this monkey pox vaccine the united states which does not produce this vaccine is placing a 119 million dollar order for 13 million freeze-dried monkey pox vaccines and you can see here that it's made by the company bavarian nordic which is a biotech company and i just like to say that i have no financial interest whatsoever in this company or any other vaccine company and of course we'll put links in the description below to all of these articles that we cite in this video and at the time of this recording we are getting news reports of new monkey pox viral cases in new york city and also in israel at this point it's unclear exactly what we can do to prevent this other than avoiding people with monkey pox if we can identify who they are but it shouldn't be lost that obviously a good immune system is going to be helpful in preventing the worst types of monkey pox clinical symptoms and this paper here published back in 2008 titled monkey pox virus evades antiviral cd4 positive and cd8 positive t-cell responses by suppressing cognate t-cell activation is a reminder that most viral issues with the human body become issues because the viruses are able to suppress our immune system according to this abstract although monkey pox virus specific cd4 positive and cd8 positive t cells could recognize that vaccinia virus infected monocytes and produce inflammatory cytokines such as interferon gamma and tumor necrosis factor alpha they were largely incapable of responding to autologous monkey pox virus infected cells now i wanted to talk to you about the strain of the monkey pox that is growing out now compared to the outbreak that was seen in the united kingdom singapore and israel in 2018 and 2019 there's a article here that shows that there is a draft sequence of the virus and it's kind of a general draft sequence so they can look at it to see if there's anything that has looked like what they're currently seeing right now and the title of this article which  is first monkey pox genome from latest outbreak shows links to the 2018 strain and they say here that the draft sequence of the virus responsible for the rapidly growing monkey pox outbreak shows that it is most closely related to strains detected in the uk singapore and israel in 2018 and 2019 however it goes on and says what isn't clear yet however is whether or not the virus has any changes that make it more transmissible in humans which could explain why the current outbreak is so widespread and by far the largest scene outside of central and west africa where the virus spreads in monkeys this could take some time to establish given that monkey pox has a large and complex genome so i would recommend once again that this is a struggle to make sure that we have a strong immune system and we've talked before about how we do that we do that by having good nutrition plenty of exercise make sure we're drinking a decent amount of water perhaps even using hot cold therapy and hydrotherapy making sure that we're getting adequate sunshine avoiding things that suppress our immune system getting plenty of fresh air getting appropriate sleep and avoiding stress we'll be keeping our eyes on the monkey pox issue as this is a developing story thanks once again for listening to medcram and for more continuing medica education topics visit us at medcram.