Hello, and welcome to today's webcast, Monkeypox, Diagnosis, Management, and Prevention. My name is Charles Volk, MD, Deputy Medical Director, Adult ICU at the Naval Medical Center San Diego in San Diego, California. I will be moderating today's webcast. A recording of this webcast will be available within five to seven business days. It will be at mysccm.org. Navigate to the My Learning tab to access the recording. Thank you, everybody, for joining us. A few housekeeping items before we get started. There will be a Q&A at the end of the presentation. To submit questions throughout the presentation, just type in the question box located in your control panel. Full disclaimer, this presentation is for educational purposes only. The material presented is intended to represent an approach, view, statement, or opinion of the presenter that may be helpful to others. The views and opinions expressed herein are those of the presenters. They do not necessarily reflect the opinions or views of SCCM. SCCM does not recommend or endorse any specific test, position, product, procedure, opinion, or other information that may be mentioned. And our speakers for today, I'd like to introduce everybody. Ryan Maves, MD, FCCM, Professor of Medicine and Anesthesiology at the Wake Forest University School of Medicine in Winston-Salem, North Carolina. Bhaviti Gaglani, MD, Assistant Professor at the Wake Forest School of Medicine in Winston-Salem, North Carolina. And Leandra Mina, MD, MPH, FIDSA, Director, Division of HIV Prevention at the National Center for HIV, Viral Hepatitis, STD, and TB Prevention at the Centers for Disease Control and Prevention. Thank you, Dr. Walk, for this, for the introduction. It's definitely a great privilege to be here and sharing the platform with other experts in the same field. So I will be briefly discussing about the natural history of monkeypox and its clinical features, and what are the severe risk factors that can make a disease very severe. So what is monkeypox? Monkeypox is a viral zoonotic disease that's caused by the infection with monkeypox virus. It belongs to the same genus family of orthopoxvirus with poxviridae that's caused by, that also belongs, that also has variola, smallpox, vaccinia, and cowpox. It has known to be previously endemic in tropical rainforest areas of Central and West Africa, and occasionally they are exported to the other regions. And based on the geographical area, there are two clades, or two types of types that can be identified. There's Congo basin clade, which is recently named as clade 1. And then there's a Western African clade, which is named as clade 2, which has subclades, clade 2a and 2b. The current outbreak is considered or identified to be caused by Western African clade. And the distinguishing factors between those two clades is the clade 1, or the Congo basin clade, is more severe symptoms and contains high case fatality rates compared to the Western African clade. Where did it all come from, and what's the further outbreak histories of monkey pox? Though being prevalent in Central and Western Africa for decades, it was initially discovered in 1958, when there were two outbreaks of pox-like disease occurring in lab monkeys. And it wasn't until 1970 that there was the first human case identified in the Democratic Republic of Congo, which was around the same time or sometime after smallpox was eliminated in that region. And so one can consider that there definitely exists some cross-reactivity between monkey pox and the other pox viruses, which would have prohibited from us learning more about monkey pox until smallpox was eliminated. And then since 1970, the human cases continue to be reported in African countries. Compared to other pox, or actually similar to other pox viruses, monkey pox was historically identified to be caused by monkeys. But truly, the specific animal reservoir for monkey pox remains unknown. Based on prior epidemiology, humans served as intermediate hosts, and African and other primates, such as monkeys, have been considered as reserves in the past. The outbreak history of monkey pox actually outside Africa happened in 2003 in the US, where there were over 70 cases that were identified. And those cases were linked to contact with the infected pet-pairing dogs. Those pet-pairing dogs were housed with the Gambian mouses that were transported from Ghana. So again, international travels and animals that have been transported had remained majority of the risk for transmission. And there were isolated cases that have been identified before this outbreak in July and November of 2021, all linked with travels. So the international travels to those countries where the transmission risks. However, the current outbreak that we are seeing is very unique and very interesting, which is known to cause transmission now with close contact with the infected person or animal, any contaminated material within the virus, and of course, intimate contact. It can be direct contact with the monkey pox, rash and scabs or body fluids from a person with monkey pox, touching objects, fabrics like clothing, bedding, towels, any surfaces that have been used by someone with monkey pox. And monkey pox itself being a DNA virus, it prevails in the environment for weeks. And of course, there is contact with respiratory secretions. There's still science learning about how an asymptomatic person can transmit the disease and how the risk or how the droplet or how respiratory secretions itself can infect a person. There's risk for placental transmittal to fetus as well. And anytime a person is infectious from the beginning of their symptoms till the rash becomes completely scabbed off with fresh layer, the risk of transmission remains. So now we're going to talk briefly about the clinical presentation. Monkey pox will look similar to smallpox, but it's milder, it's less contagious. The incubation period is somewhere from 7 to 21 days. And the initial period will be, there will be symptoms such as fever, back pain, generalized aches, fatigue, and lymphadenopathies. And lymphadenopathies are actually very specific to monkey pox compared to smallpox, which lags it. Once the prodrome period starts, and then the rash develops, the rash can develop anywhere from two to four weeks. And there's different stages it can progress. Sometimes there won't be any prodrome period, and then the person can only have rash as the initial manifestation. The rash can appear anywhere in the body. It can be included in the palms and soles and endogenous regions. The rash is deep-seated, they're firm, well-circumcised, they're umbilicated. And one thing interesting about the rash of monkey pox is that all of the rash, the rash are particularly in the same stage of the eruption. And when you think about rash like this, we always have to think about the clinical mimics. And the higher inline or entity of the disease, which is very similar to monkey pox, is varicella. And so a clinician should always think about differentials with sexually transmitted infections while evaluating a person. Identifying their risk factors and appropriate testing is very crucial. Usually the disease is known to be limited, very self-limited, within two to four weeks. But there are cases of severe disease that can happen. And those happen in populations that are high risk. So the high-risk population includes those who are in severe immunocompromised states, children aged less than eight years old, pregnant women, breastfeeding, and HIV. Now there are very interesting stories about HIV and studies that have been identified. HIV itself does not necessarily cause the risk for monkey pox. However, those with poorly controlled HIV, with low CD4 counts, not on any treatment, definitely have severe risk of the disease. Monkey pox is a dermatophilic virus. And so with cutaneous spread, anyone with significant active exfoliation, dermatological condition itself can have severe presentation of monkey pox. And based on the location and size of the lesions, those who are at risk of strictures, fistula, especially when there are rash erupting in the rectal area, the anal area, that can have a high risk of severe disease. So severe cases can happen. And the severe disease now can present with sepsis, hospitalization. It also depends on the evidence of viremia and how much the risk exists. And we talked about the location and type of the lesion, any areas that have high risk of scaring or strictures, particularly eyes, mouth and sparing, and the endogenital areas. And this is how we're going to see admissions coming in the hospital, maybe in the ICU as well. And especially when we talk about protecting their areas, they are at risk of area obstruction if they have severe lymphadenopathy. This is all based on prior epidemiologies and cases that we have been seeing. Secondary bacterial infections definitely possess one of the factors that complications based on the cutaneous lesions, which can serve as a port of entry. Other side, if other complications that's been identified can be pneumonia, gastroenteritis, encephalitis. And rarely we have seen cases with myocarditis. The historic case fatality ratio is somewhere from three to 6%. With this current outbreak, we still need to identify cases. We still have studies to look for in terms of how the cases are prevailing and how much complications we are seeing. And so far in the United States, we have zero deaths that have been identified last week. So I'm going to end my presentation here and going to pass it on to Dr. Ryan Mabes for further presentation. Thank you very much for this opportunity and I hope to see everyone in the Q&A. All right. Thank you very much, Dr. Gaglani. My name is Ryan Mabes. I am a professor of medicine and anesthesiology in the sections of infectious diseases and critical care at Wake Forest University in Winston-Salem, North Carolina. So I'm going to follow on from where Dr. Gaglani was speaking and lead more into diagnosis management and then hopefully prevention as well. All right. So as Dr. Gaglani talked about, you know, the diagnosis, obviously the first step to diagnosis is finding a patient with compatible exposures and a compatible syndrome. So, you know, new rash and lymphadenopathy are going to be key features, but they're certainly not universal. And one thing that we have seen anecdotally here in North Carolina is that the lesions are often not on places where people are, where patients are necessarily going to be able to display their rash easily. So, you know, certainly patients who are going to have, you know, pain around the genitalia, pain around the anus and rectum or on their backside. Those are places we really need to make sure that we're looking at carefully. The lesions are typically painful once they arise. So that is at least a useful, useful guidance. And the presence of lymphadenopathy with them is helpful. Although bear in mind that things like acute herpes viruses, particularly new onset HSV infections can also present with lymphadenopathy. If you can get a compatible exposure history, that is helpful. The great majority of cases identified have had some degree of intimate contact with another patient who ultimately turned out to have, turned out to have monkeypox. And then again, a high clinical suspicion. So the cornerstone of diagnosis other than clinical presentation and compatible examination is going to be a PCR. And that PCR is a pan genus PCR for orthopoxviruses. So in the compatible, in a compatible setting, a compatible, excuse me, a positive orthopoxvirus PCR is effectively going to be a diagnosis of monkeypox. Of course, human smallpox hasn't happened for decades. Hopefully we keep it that way. Cowpox is a very unusual disease in humans. And then the vaccinia virus is associated with the older ACAM smallpox vaccine that in that case, you should have a history, a recent history of vaccination. You can get this, originally it was available primarily through the CDC or laboratories in the laboratory response network, which is organized by the CDC and includes state and regional public health laboratories. Now commercial laboratories are starting to offer the orthopoxvirus PCR. My hospital actually just got some results back from LabCorp the other day. So very handy. So ideally the way we get these is we take at least, we identify at least two lesions and test them both. And you really need to get two specimens per lesion, meaning two swabs per lesion. So in order to obtain these, and there's some very nice graphics showing how to do this step-by-step on both the CDC's website, also NETEC at N-E-T-E-C dot org, the National Emerging Special Pathogens Training and Education Center has very nice videos describing this. But essentially it takes synthetic swabs, meaning polyester or Dacron, not cotton, not anything with organic fibers, and then apply firm pressure to the lesion and swab vigorously. Have to get some cellular material on there. You don't need to specifically try to unroof vesicles, but if you're doing this right, they're going to get a little bit unroofed. Take these swabs and place them separately into viral transport media. Now if there aren't any active, say, vesicular or pustular lesions, you can get a crusted over lesion. It's a little bit different there in that you need to use sterile forceps or some sort of blunt device to try to remove all or at least a good size piece of crust, which I ideally be at least four by four millimeters in size, and place that in a dry sterile container. And laboratories should be able to run PCR off of that. Although if you're working with a commercial laboratory, it's worth checking to make sure that they accept that kind of specimen. So in the diagnosis, we do have to remember that there is a differential in play here. For example, at Wake Forest, when we have sent off muckypox or orthopoxvirus PCRs, we have generally sent HSV and VZV PCRs from the same lesion. As Dr. Gaglani pointed out, unlike varicella, the lesions of muckypox tend to be at generally the same stage of development. Whereas we'll say with varicella, the lesions occur at different stages of development. So you'll have crusted over lesions next to fresh lesions with varicella. That is a feature in general of orthopoxvirus infections. We see, we say we, we historically as a medical community saw the same thing with smallpox. Syphilis certainly can. There've been a number of cases of muckypox and syphilis co-infections. Disseminated gonococcal infections can overlap as well in that people tend to be reasonably sick, generally febrile, and will have pustular lesions more often around the joints. And then molluscum contagiosum, which is another poxvirus infection. So if you have someone with a suspected case and they're in the hospital, they do need to be in some level of appropriate precautions, pending test results. Those precautions are very similar to the precautions we use for patients admitted to the hospital with suspected or confirmed COVID-19. Patients should be in a single occupancy room. You don't need to have a negative pressure room for this. If you have it, it's fine, but generally just a single occupancy room is sufficient. However, for healthcare staff entering into that patient's room, it's gown, gloves, eye protection, and an N95 are equivalent, very much like with COVID-19. Now the big difference here is that muckypox appears to be considerably less contagious than COVID-19, but nonetheless, as we are learning about this new disease, the prudent thing to do is to use this higher level of respiratory precaution and contact precautions as well. All right, so therapy. Unlike the last great novel viral outbreak, we are coming into the muckypox epidemic in a stronger place therapeutically, because there are well-established drugs and there are well-established countermeasures that were already available. These were largely developed in response to concerns for the use of smallpox and bioterrorism or some other natural reemergence. But fortunately, there's enough similarity between smallpox and muckypox that these agents appear to be effective. So the first question is, who do you treat? As Dr. Gaglanti described, the mortality from muckypox in the older West and Central African outbreaks seem to be relatively high, somewhere in the 3% to 10%, depending on the series and the clade and the population under study. We've been very fortunate that there have been no truly confirmed deaths in the United States from muckypox out of 15,000 or so cases confirmed. There are a couple of potential cases. I read the paper today that there may be a muckypox death being reported out of Texas right now. But nonetheless, the question becomes, who do you treat? So certainly anyone with severe disease or major complications. If someone were to develop a sepsis-like syndrome, if someone were to develop an encephalitis or had severe nausea, vomiting, or diarrhea that was leading them to be hospitalized, the significantly immunocompromised host should almost certainly be treated. Now, immunocompromised is a sliding scale. So the recent bone marrow transplant recipient or the recent solid organ transplant recipient, a patient with advanced HIV infection and a CD4 count less than 200, those people should clearly be treated. On the other hand, if you're looking at someone who has a well-controlled HIV infection, a high CD4 count, and undetectable viral load, it's not clear that they're at any particularly greater risk than the general population. And those people will generally, it appears, based on the currently reported observational studies, that those individuals will recover spontaneously in the majority of cases. Young children are recommended to be treated. And a pregnant woman should probably be offered treatment. Women have been, at this point, a relatively small minority of the number of cases of muckypox. So we don't have as much data in pregnancy as we do for other populations. Someone who's got an infection in a highly anatomically sensitive site, I would say on or near the eyes, for example, would absolutely be someone you'd want to treat. Of course, now, it's worth noting that this is an SCCM presentation. And we're thinking about people who practice in a critical care setting. I would argue that most cases of muckypox that we encounter in a critical care setting, these patients will probably benefit from treatment in one way or another. It may be that the muckypox is incidental and not their presenting syndrome. But nonetheless, having a mechanism to treat them may have some infection prevention benefits. And our patients in the ICU who have incidental muckypox are likely at risk for more severe consequences of infection just due to the general immunosuppressed state that comes secondarily from critical illness of whatever cause. So the principal agent that we are using right now is tecovirumat. So tecovirumat is an inhibitor of the viral P37 protein. And this protein has multiple functions in the virus. But one of the principal ones is that it is key to the release of new virions from an infected human cell. So this drug was approved based on the FDA animal rule, meaning that it showed efficacy and safety in animal models because, obviously, it's a drug we were developing for smallpox. We had neither a way to do human studies, nor was there any ethical way to go and do muckypox human challenge models, for example. However, it turns out that this actually seems to be a very safe and well-tolerated drug. There have been a few small series coming out. Most recently in JAMA, just a series of 25 unselected male patients treated at the University of California in Davis, averaging about 40 years of age, a substantial number of them living with HIV, 40% of patients resolved after seven days, 92% after 21 days. And other than some principally GI side effects and headache, which can be difficult to separate from the effects of muckypox itself, patients did very well. There are no randomized controlled trials for muckypox and tecovirumat in the general risk population yet. Those are going to be coming relatively soon. So tecovirumat has another advantage that it's available both as an oral or intravenous formulation. Typical course is 14 days. A couple of patients in the UC Davis series in JAMA received 21-day courses. So this is available under an expanded access IND protocol, which is held by the CDC. So there are different mechanisms to get this. And the advantage of this is that you don't have to have a separate institutional IND to use tecovirumat. So how do you get access to it? It's a fairly complex process, but I will say CDC has made it increasingly easy for us over time. The most efficient way is to contact your state or county public health for guidance. They may have an existing pathway within your local public health authorities. You can call CDC directly for assistance. Their emergency operations center number is 770-488-7100. The forms and instructions are also available at this website, the CDC's website that you can check out. It explains how to obtain tecovirumat. All right, so tecovirumat is not the only agent available. There are some other therapies. So sodofavir is a long-acting IV nucleotide analog, a relatively older antiviral. Many hospitals will already have sodofavir in stock. It has broad activity against DNA viruses. Its actual approval is for CMB retinitis in patients with HIV infection. So sodofavir is only a parenteral drug. It's administered generally about once every two weeks. You have to co-administer it with probenicid, which is an oral agent. The main use of probenicid in sodofavir is that it is protective against the not-insubstantial nephrotoxicity of sodofavir. Sodofavir has in vitro activity against pox viruses. There are no RCTs guiding it. That being said, you know, one could hypothesize that in a seriously ill patient whom one needed to treat very quickly, sodofavir may be an option for something you could use while you were trying to get tecovirumat. And I should also be honest that there are no comparative studies of tecovirumat versus sodofavir for pox virus infections. So brin sodofavir, or sometimes you'll see it in the older literature as CMX001, this is an oral prodrug of sodofavir. It is considerably better tolerated. It does not appear to have the nephrotoxicity. It is not currently available for the treatment of monkeypox, but there is an EAIND in development, and I think eventually brin sodofavir will become available for this purpose. Once again, we don't know if brin sodofavir is better, worse, the same as tecovirumat, but that may become a second option. Lastly, there's anti-vaccinia immune globulin. So this is an FDA-approved agent for the treatment of vaccinia-related complications. Remember that the older smallpox vaccine is a live virus with vaccinia, which is a derivative of cowpox and which in turn is closely related to smallpox and monkeypox. Patients who receive the live vaccinia virus vaccine, the ACAM2000, are at risk for some degree of dissemination and more severe infections as a consequence of vaccine-derived infections. And this is a potential therapy for that. This might be effective as prophylaxis, especially for patients with severe T-cell deficiencies or dysfunction who may be expected to respond less well to vaccination. And then hypothetically, could it be used as treatment in severe cases? Short answer, maybe. So in terms of other aspects of prevention, it's very good that we have good therapies, but how do we just keep from getting sick in the first place? So after high-risk exposures, it's recommended that patients have 21 days of monitoring, not quarantine. They're free to move about in society, but they should monitor themselves for new onset of infections. Those can be respiratory infections. Those can be infections. Those can be signs and symptoms relating to rash, fever, lymphadenopathy, and the like. Suspected or confirmed cases in the hospital, like I said before, single occupancy room, airborne infection isolation rooms, such as a negative pressure room, these are optional for monkeypox, except unless you're doing an aerosol-generating procedure, such as intubation, delivery of nebulized medications, bronchoscopy, or the like. Gown gloves, eye protection, and N95 are equivalent, again, are also standard. Very much like COVID, we should all be very comfortable with this at this point. Now, how long do you continue precautions? So this isn't like COVID, where I can say, you know, 10 days or 5 days or 21 days, depending on the population and the severity of illness in question here. This is largely a clinical call, meaning that you need to continue precautions until all of the lesions have crusted, those crusts have separated from the skin, and you see a fresh layer of healthy skin is forming underneath. So once all the lesions have healed, and you have fresh skin overlying them, then you can take that person out of precautions. This is obviously not a thing that the average person in critical care is going to have a ton of experience with, at least in maybe marginal or borderline cases. This is very much one of those situations where getting your infectious disease consultants and your infection control staff involved in the decision to remove someone from isolation precautions. Right, how about vaccination? Again, we come into this outbreak in a pretty good place from a vaccine standpoint, in the sense that we have not one, but two highly active vaccines already available and already approved. And really, the challenge has just been getting us in a position where we can have enough vaccine available and have stable mechanisms for vaccine outreach and delivery. So the current leading vaccine that we have, this market is Ingenios. It's in the United States. Imvamune or Imvanex are its names in Europe, the UK, and Canada. It's the same vaccine. It's made by Bavaria Nordic. So this is a replication-incompetent vaccinia virus, meaning this is a virus that can infect a human cell, but it cannot replicate in a human cell. So you get a good humoral immune response. You get a good T-cell immune response, but you don't have the challenges of disseminated infection, auto-inoculation, transmission to high-risk hosts like you have with the older smallpox vaccines. So this is FDA-approved for smallpox and monkeypox prevention. It can be given as post-exposure prophylaxis within four days of exposure. It is safe to give in immune-compromised hosts, unlike the older smallpox vaccines. It's a two-dose series, generally four weeks apart. The usual dose is 0.5 mils given subcutaneously. There is some emerging data that you would use smaller amounts of vaccine, so only 0.1 mils given as an intradermal dose. That is an option during the public health emergency. Whether that will be the preferred mode of vaccination in the future is unknown. This is estimated as having at least an 85% efficacy against monkeypox. Again, remember, this is not a monkeypox vaccine per se. This is a smallpox vaccine. Availability has been increasing. We've actually started at Wake Forest a vaccine clinic in our ID clinic. It is safer and generally seems to be much better tolerated than older smallpox vaccines. The downside is it's a two-dose series and not a one-dose series. The other vaccine, just to include for purposes of completeness, there we go, so ACAM2000. This is a live attenuated vaccinia virus. It's the same vaccine strain as JYNNEOS. It's the Oncora strain of vaccinia. This is an older vaccine. This is the vaccine that I received when I was in the military. It is highly effective, but there are multiple contraindications. The big thing is that it is giving you an active pox virus infection at your vaccine site. That active pox virus vaccine, excuse me, infection can be transmitted. It can be auto-inoculated to yourself by touching the lesion, then touching the other part of your skin, touching your face, touching your eye, and it can be transmitted to others if you're not very careful about wound care. So even a compromised hosts are not eligible to receive this vaccine. Patients with eczema or other chronic skin diseases are at increased risk of complications of auto-inoculation. Pregnant women can't receive it. And then if you live in a house with people who meet those criteria, so for example, if you are an adult and you have a child with eczema in your home, you should not receive the ACAM2000 vaccine. There are some fairly, I wouldn't call them terribly complex wound care infections, but it does require attention to detail, regular changing of the dressing over it until it crusts over, and you're not considered to be immune until, if you see this graphic from the FDA, until the lesion has crusted over, the crust has fallen off, and you see healthy skin growing underneath, that's when you're considered to be immune from that. So it is effective. A number of people have received this in childhood or through military service or other pathways of having gone, and those people are generally considered to be protective, at least if it's in the last few years. But JYNNEOS is really the product that we are encouraging folks to use. Right now, there's not a general recommendation for clinical staff to receive it. That may change over time, but right now, really our emphasis is getting it to high-risk populations. And I believe Dr. Maynard will talk more about who those high-risk populations are and how we're targeting them for vaccination and other prevention efforts. So thank you very much. Thank you. Good afternoon, everybody. And thank you so much, Dr. Mabes. And thank you, Dr. Gaglani, for giving us such a comprehensive and thoughtful presentation on the clinical diagnosis, management, and prevention aspects of the monkeypox. So today, I'll give you an overview of monkeypox and the current situation. As CDC and its partners work to prevent the spread of the disease in the United States and around the world. So as you see here, monkeypox worldwide started early on in May 12th. And cases have increased progressively throughout the past three months or so. And it appears right now there's some leveraging in the number of cases that we are seeing worldwide. Countrywide, the United States represent the largest number of cases, followed by Spain, UK, and Brazil. As of May, between May and May 16, what started with three online confirmed cases of clade 2 monkeypox in the UK, one in one traveler, two in two household members, and four individuals reported being sex with men has really expanded to be a global outbreak. As of August 29th at 5 p.m., 48,844 total confirmed cases of monkeypox, of which 48,401 cases have been reported for 92 non-endemic homies. In the United States, as of August 29th, we have reported about 18,101 cases. And here you can see the top states have reported the highest number of cases in California, New York, Florida, Texas, Georgia, Illinois, and Pennsylvania reporting the highest numbers. Trends in new cases reported to CDC began to rise in July. In August, they broke the 1,000 cases in a day. For the most part, reported case numbers in the states haven't aligned very well with the size of the populations. In general, most populous states also have reported more cases. This chart is also on our website and is updated regularly. A recent case series of 528 individuals with monkeypox infection dropped from 43 sites in 16 countries provided important data regarding the populations most heavily affected at this point on the outbreak. The median age of 38, over 99% of cases were male, 98% reported sexual contact with other male, and 41% reported living with HIV, and almost a third were co-infected with another sexually transmitted infection at the time that the monkeypox was diagnosed. We see the global demographic characteristics as of August 29, again, with a median age of 36, predominantly male cases, male interacts with men, and sexual transmission continues to be the primary form of transmission. The epidemic in the US has similar characteristics to the international study just presented. While there are still a lot of data missing at this point, among men who have data available, over 90% reported male-to-male sexual contact. Similar to the international data, a significant proportion of individuals diagnosed with monkeypox in the US are living with HIV. And we can see here that most cases of monkeypox, although there are cases pretty much reported almost any age group, most cases are between the ages of 21 to 45 years old. Each week, jurisdictions report cases data to CDC. 47.5% of cases have sufficient data to analyze the race and ethnicity. This slide shows how the race and ethnicity distribution has changed. It shows that black and Latino people are bearing a disproportionate burden of cases. So it's important that we incorporate equity into every aspect of our work. In the most recent week of reporting, which was August 14, the three groups that accounted for most cases were black persons, Latino persons, and white persons with 33.2%, 31.8%, and 30.6% of cases, respectively. Here, we see data from our MMWR that basically reports on most common symptoms of cases reported in the US, with rash, malaise, fever, and chills being the most prominent symptoms reported. But it's important to know that a large proportion, almost 25%, a quarter of individuals reported some kind of rectal symptoms. Including rectal pain. That should be an important consideration, as mentioned before by Dr. Mapes and Dr. Deglani, for concurrent sexually transmitted infections like HSV, chlamydia infection, or gonorrhea in the rectal area. So the good news is that, again, by Sesha and other members of Maine, who are taking steps to protect themselves and their partners from occupants. From the beginning of the pandemic, the CDC has worked with communities, these communities affected, to message about how to protect themselves for monkey pokes. And what we have seen in this survey, in the data which was published in the MMWR, is that about 48% of MSA members should make a report on reducing, in this survey, a report on reducing the number of sex partners. About 50% of them reported reducing one-time sexual partners. And about 50% of them reported reducing sex partners met on dating apps or sex venues. And this is particularly important. Last Friday, we reported in MMWR, in some of our modeling work, of sexual infectious transmissions between men indicate that one-time partnerships, which account for 3% of daily sexual partnerships, and 60% of daily sexual acts, account for approximately 50% of any monkey pokes virus transmissions. So a 40% reduction in one-time partnerships might delay the spread of monkey pokes and reduce the percentage of persons infected by 20 to 31%, which somehow may explain why monkey pokes cases may be leveraging up for the time being, giving us some time to provide vaccination to those individuals who are at risk. And this concludes my presentation. Thank you very much for your attention. Looking forward to the questions and answers. One question, and I think we can, the three of us can lob this back and forth between each other is, can the virus live in inanimate objects? And I think the questioner from the audience is asking about fomite transmission and what do we know about fomite transmission? And I think then probably between the three of us say, what are the implications of that for an infection prevention standpoint? Dr. Gaglani? Yeah, absolutely. That's a good question. So like we mentioned, monkey pokes virus being a DNA virus and it's the capacity to live in the environment for weeks. And so anybody who has monkey pokes and who has touched any objects, including bedding, clothes, linens, any objects, and something we recently saw in a household back in Missouri or somewhere in Midwest is that those virus, when you have any part of your body fluids or the rash itself, or, you know, depending on the stage of that rash. Once that virus, once we come in contact with that object that's been touched by patient, person who has monkey pokes, the risk of transmission is there. How long the virus lives for, again, it's a really good question, but again, the transmission can happen anywhere from two to four weeks. It's where we see with incubation period being from seven to 21 days. And that's where, you know, the infection prevention measures comes even at home, you know, sterilizing those objects, isolating the person who has been identified to have monkey pokes and so forth. Dr. Mena, what is CDC saying about this? If I may impose on you. So if I can add, yeah, I totally agree with Dr. Garlani in terms of being a DNA virus, so very resistant to environment. We also know that monkey pokes are very susceptible to usual, you know, cleaning products, you know, at home. You know, and we published recently a case study in a home in Utah, you know, where two individuals were living with monkey pokes, you know, after 14 days living with monkey pokes, CDC team went in and took environmental samples. And what they did is that they found a significant, you know, monkey poke genetic material. They also found that porous surface, you know, are more likely to retain these genetic material. And that was 21 days out, you know, from when the symptoms started. But this is a house where individuals were basically washing their hands very frequently and disinfecting and cleaning. And although they found the genetic material, they couldn't find replicating, you know, virus that was able to replicate, in replicating a viable virus. So again, we know it's possible, and we know that infection control, you know, measures, you know, like cleaning and disinfection, washing their hands are important ways to decrease the transmissibility. Yeah, and we certainly do know from some darker corners of history that orthopoxviruses can persist in the environment for a long time. There's a fairly notorious cases of smallpox transmission to Native American groups being deliberately transmitted, I guess, via fomite infected blankets and the like back in the colonial period in North America. So yeah, whether that's actually possible in monkeypox, I think remains unclear. But while we're learning about this new disease, I think probably maximally, or at least appropriate precautions with a tendency to round up a little bit is reasonable, certainly for those of us involved in direct clinical care. Do we recommend that all healthcare workers become vaccinated? Z, what do you folks think? I gotta take that one. You know, I think the general risk, you know, so far for healthcare workers appears to be low. I think there has been one case, you know, of someone who was administering a monkeypox vaccine who after self-inoculated and develop a lesion in the finger, and that was in Europe. But the risk, you know, generally is low. For healthcare professional vaccinations, primarily for laboratory staff that are working with orthopoxviruses, and right now, because we don't have enough vaccines really to give to those individuals who are the highest risk, right now there has been no decision about vaccination of our healthcare professionals. Yeah, yeah. No, and I certainly agree. I mean, I was vaccinated about a decade ago with ACAM against smallpox, and I suspect that people, you know, like myself, probably have some degree of residual immunity from that. But in terms of how we prioritize people in direct clinical care, the risk seems extremely low. And while we're in a time of needing to prioritize groups at maximal risk, MSM in particular, I think we're probably not the top of the things to do list, except for those of us involved in direct laboratory work, or perhaps vaccination campaigns one could imagine there. Dr. Gaglani, any thoughts? No, I totally agree with you. And to a separate note, I would say that, you know, of course, in this outbreak, we haven't really seen any healthcare associated infections, but something, it can also be a risk of transmission if adequate infection control and prevention measures are not followed. So I believe beginning with that, when suspicion cases, isolating them, maintaining those precautions while in an inpatient settings with everything the healthcare workers hopefully should be able to avoid that infection within the healthcare workers. Yeah, absolutely, absolutely. Well, so one other question is, so sort of related to that or adjacent to that, is we are targeting specifically as a public health standpoint, men who have sex with men as the highest risk group. Are there any other groups that we need to be targeting specifically? I can think of a few ones, kind of in our ID clinic at Wake Forest, you know, a prep group, a clinic at Wake Forest, a, you know, a prep consult kind of automatically becomes, that's a pre-exposure prophylaxis for HIV prevention consult, kind of automatically becomes a, have you thought about getting a smallpox, monkeypox vaccine consult? But in terms of other groups, I'm thinking perhaps female partners, female sexual partners of MSM would be one example. Any other groups? You know, I can say, you know, the number of cases in women are relatively small, right? And initially many of them, at least in the U.S. were connected to other MSM, you know, but then we, although we have had a little bit over 200 cases of women, the number, and at the same time, we're seeing an increase in the number of cases from men who do not report sex with men in the past, you know, 21 days. It's really not clear what's going on there, right? Because it could be that men are less comfortable as this, you know, pandemic is expanding into other populations that are more stigmatized, right? Or are less comfortable in disclosing, you know, same-sex behavior. And the numbers in women have really not changed substantially or proportional to the changes that are happening in men who don't report sex with men. And these data are very incomplete, yet the risk factor for many of these women still appears to be sexual contact. Yeah. Yeah. Thank you, sir. Dr. Gaglani, are you still with us? Yes. Yeah. Oh, I'm sorry. Go ahead. No, I was gonna say, I totally agree with Dr. Minha in terms of the vaccination recommendations. Again, our MSM population still remains at high risk. And so I believe our target initially should be beginning with them. Yeah. Now, of course, it occurs to me, this is an SCCM webinar. We probably should think about some critical care aspects of this. As we've discussed earlier, we've been fortunate in the current outbreaks that this is, that the mortality has been very low and the impact on critical care, unlike COVID-19, has been fairly minimal. But it's worth us, I think, us thinking about what those impacts might be, right? What are the potential impacts of this? And Dr. Gaglani, what do you think? Like, what do we as intensivists need to know? Yeah, so very good question, Ryan. Definitely, you know, when you have a critically ill patient coming to the ICU with rash, the differential needs to be broader. We need to think out of the box. Certainly, sometimes, I mean, hopefully they're not that sick, but sometimes those patients might not be even in a condition to give us any history if they're critically ill. And so having monkeypox in the differential, along with other sexually transmitted infections that can present a similar rash. And then really thinking about their complications that can happen. And we briefly talked about how, with those lesions being, depending on the location and size of the lesion, for example, in the mouth, in the pharynx, the severity of lymphadenopathy if they can obstruct the airways. And so airway protection in that way, along with maintaining the precautions, then, you know, we still, the patient still remains and we haven't really confirmed it. And so those can become really challenging, especially when taking care of those population in our ICU. And other differentials in some of their, in encephalopathies, they can have encephalitis, a typical pneumonia presentation. Surely, you know, as I do wanna be a great antibiotic store from something we have learned from the COVID era, but those rashes and lesions have risk of secondary bacterial infections. Then a thorough physical exam. I mean, we cannot emphasize more on that. You know, when we see the generalized rise in the body, look into their genital areas, look into the anal areas. I mean, the rash can still be present with other infections spreading, like scleral cellulitis, proceeding to abscesses and so forth. Thank you very much. Dr. Mena, has CDC been gathering any data on hospitalizations, Rick, related to monkeypox, or are we still kind of early in that phase right now? You know, we have, and we know that hospitalizations have been relatively low, and not only in the U.S., but also in Europe. But they have happened, I mean, largely for pay control. Yeah. Thank you, sir. I appreciate that. All right, can everybody hear me now? Okay, excellent. All right. So, excellent, all right. So, a couple of questions that I had listed here. Thanks for commenting on the critical care aspects. Yeah, I saw from the New England Journal article last week that out of the 70 people who were hospitalized in there, in their series, two out of 70 had myocarditis, one had epiglottitis, and did get tekevirumat. So, thank you, Dr. Mavis, you kind of had commented on a lot of those aspects. So, I'm sure there'll be much more to be coming there. Any ideas as to how contagious this is respiratory-wise, or is there a period of time where it's most contagious from a respiratory perspective? Can I throw that out to the panel? So, I would say, again, that's still something that we're trying to really look into it. Like, you know, if it's a droplet, if it's a droplet nuclei, if it's gonna be like an airborne way of transmission, how big are the nuclei, how much is the risk remains? And that's why, if in a situation that it's doable, airborne isolation is recommended, especially while we are going to do any kind of procedures related to airways or respiratory secretions. But if not, then at least droplet isolation is recommended. Now, it can spread, the transmission can happen with kissing, any kind of face-to-face contact during intimacy and so forth. And so, again, the question still remains. I would love to hear what Dr. Mina and Dr. Mavis have to say further. I will just say, within the context of the current public health emergency, it doesn't seem as though respiratory transmission has been a major feature of transmission, that the transmission networks we see seem to align more with intimate contact. And I saw there was another question in the chat about whether this was a sexually transmitted infection. I don't think it meets that definition precisely, but certainly sexual contact is a route for transmission. One can say the same thing about a variety of infections. You can say the same thing about Shigella, for example. But in terms of the epidemiology of transmission, it does seem to stay more linked to intimate contact. So from that standpoint, if there's respiratory transmission, it is not the major factor in spread right now. Is that a fair statement, Dr. Mina? What do you think? Yeah, I totally agree. I think the epidemiology really supports the idea that at least the current outbreaks, in the current outbreak, the virus is primarily transmitted through close, intimate contact, skin-to-skin contact between people. Now, when it comes to the question to STI, I think it's an interesting question, one that is causing a lot of debate for a number of implications. In general, we consider a pathogen to be human STI, right? Very often, it depends on the sexual relations between human beings. And when sexual relations are the primary links for survival and proliferation. And we have in our textbooks, right, over 30 different microbial agents that can be transmitted sexually. And although just a minority, you know, sexual transmission is their sole and dominant way of transmission, like you have for gonorrhea or chlamydia. Yeah, but for most of them, you think if you see the current outbreak, it's really behaving, in many instances, as an STI, at least now. You know, I think it's important that we continue to be vigilant, you know, and follow, you know, and do comprehensive histories in cases to make sure that we can detect when this outbreak may expand to other populations. All right, thank you, everybody. We have a couple of questions here, which are both somewhat similar. So one, does resistance develop easily to tecovirumat, and then does this virus also have the ability to sort of easily mutate like COVID, which kind of are a little bit together, since resistance and mutation are together. So if I could throw out to the panel thoughts on the mutability of this virus and then resistance to our known antivirals. I would say for tecovirumat, who knows? There's not enough clinical experience to say I'm not aware of any in vitro generation of resistance being seen in the laboratory. And is the virus particularly mutable? I mean, all viruses are somewhat mutable, right? All organisms are, to the extent that a virus is a living thing, is capable of mutation. But, you know, over, certainly over, and there are clades, there are distinct clades of monkeypox that exist, but, you know, smallpox was a remarkably genetically stable virus over a very long period of time. I don't, and DNA viruses generally aren't quite as mutagenic as RNA viruses. So the answer is probably not, but maybe? All right, excellent, thank you so much. Question here, is there a comment on the best sanitizing solution to clean up these fomites, bleach, alcohol, other chemical? Any thoughts from everybody? My understanding is just, you know, general cleaning products work very well for orthopoxviruses. Okay, excellent, anything sounds good. All right, do we have any idea how long people who got the ACAM2000 vaccine would have some residual protection? I can start, you know, we don't know that, you know. I know from some of the early series from Spain, I remember at 12, you know, some of the very earlier series, I mean, about 20, 25% of individuals, you know, that they had, young men had received the smallpox vaccine because of the prior history of the military, yet it was not fully protected. We don't know how they may have some partial protection that may ameliorate, right, the symptoms that people may develop. Okay, yeah, so some other questions here, which is the same about how long do these vaccines last. Some questions about, do the rashes and lesions cause long-term pain syndromes? So to the best of our knowledge, no, this isn't post-traumatic neuralgia like you see with varicella and shingles infections. So not that I'm aware of, although it wouldn't surprise me if there are exceptions to that. Dr. Gaglani, what do you think? Yeah, I totally agree with you. I believe recently we had a case where a patient needed to be hospitalized, particularly for pain management, and that patient, we ended up giving a temporary med or T-box, and the pain improved, the lesions started getting better. So I agree, I do not anticipate or something that we have not seen yet of it being like giving post-traumatic neuralgia. And then any comments from the group about the acute infection pain? Is there any agents that are, seem to work better than any others? Any thoughts about topical, systemic opiates using Marantin NSAIDs, any thoughts? From my clinical experience of the two, three cases that I encountered, the patients did require opioids initially for pain. Neuron synthesis mechanism itself takes time to act on to it. But again, it wasn't something that it was a drastic amount of pain meds that required drips or so forth. And so, of course, those skin lesions with it being cutaneous spread, I mean, topical opioid ointment did help to our patients. So certainly it's gonna be individualized, but starting from topical, still any source of pain management in terms of non-opioids to begin with, and then opioids is needed help. Excellent, thank you. Do we know of any trials that are enrolling right now? Oh, go ahead, Dr. Mena. No, no, well, I know that there are a number of studies that are being done in San Francisco in different parts of the country. There's a clinical trial looking at tecovirumab. So yeah, there's several trials. I mean, trying to understand the natural history of monkeypox and the efficacy of tecovirumab and also the efficacy of the vaccine. Yeah, I mean, I think it would be a challenge to do a truly double-blind randomized trial in a high-risk individual, in someone with advanced HIV or progressive disease or someone who's in the intensive care unit. And I think probably the early RCTs are going to be focusing on what we call average risk individuals who are immunocompetent, generally otherwise in good health to assess whether or not they both have clinical and virologic resolution more rapidly with tecovirumab. Yeah, but those are just getting started. Okay, excellent, thank you so much. Looks like that's about all the questions that we have time for today. Thank you to all of our panelists. Thank you for having us here. Yeah, thank you so much, everyone. Thank you so much. Thank you. And thank you to SCCM for giving us this opportunity and thank you to Dr. Volk for moderating. Everyone have a great day. Thank you, everyone, goodbye. Bye.

Monkeypox

Viral zoonotic disease

Monkeypox virus

Transmission

Fomite transmission

Symptoms

Severe cases

Complications

Treatment

Prevention