Monkeypox: Old Foe, New Movements

Monkeypox: Old Foe, New Movements
Aired October 12, 2022

Ashley Peery:
So hello again, my name is Ashley Peery and I'm an educator at Smithsonian's Natural History Museum. I'm a blonde-haired woman wearing a cream-colored sweater and a red scarf. I'm sitting in front of a background with a wall showing some framed schematic drawings, and on your screen is an image from an electron microscope of cells infected with monkeypox, as well as the date, time, and title of today's program, Monkeypox: Old Foe, New Movements.

This is the first program in our Shared Planet, Shared Health series, which is a monthly webinar series exploring the connections between the health of humans, the health of animals, and the environment, also known as One Health. So the series is a continuation of programming connected to the exhibit Outbreak: Epidemics in a Connected World. That exhibit is currently closed to the public, but I'm very excited to share that it will reopen in a new form in early November, and we're going to keep the One Health conversations going with this new series.

So whether it's your first time joining us, or you've attended a Natural History webinar before, we're so glad that you're here. And before we get started, I have a few housekeeping notes. So first, this discussion offers closed captioning. You can turn the captions on or off, and you're going to do that using the CC button, which should be located at the bottom of the Zoom interface. You might need to click More in order to see that CC button. As you have questions, even if you think of them during the presentation, go ahead and throw them into the Q&A box. That Q&A box is going to be at the top or the bottom of your screen, and we want to get through as many of your questions as we can. And the Q&A goes really fast, so get your questions in as they come to you. The Q&A box is also where we're going to share links with you during the program, so keep your eye out there.

And we're going to start today's program with a presentation from our speaker, Dr. Agam Rao. And then I'm going to join her back on screen when it's time to take your questions. So let's introduce today's speaker.

Today's speaker, Dr. Agam Rao, is a medical officer with the Poxvirus and Rabies Branch of the U.S. Centers for Disease Control and Prevention. She was a CDC Epidemic Intelligence Service officer in 2009, and since then her focus has been on the clinical presentation of rare and life-threatening pathogens. She also leads outbreak investigations and develops national vaccine guidelines, including recommendations of the Advisory Committee on Immunization Practices. Dr. Rao has served in several roles of CDC's multinational monkeypox response. She leads the Epidemiology Task Force, serves as a Subject Matter Expert for the Clinical and Vaccine Task Forces, and leads the Advisory Committee on Immunization Practices' Monkeypox Vaccine Work Group. Dr. Rao is a captain in the Commissioned Corps of the U.S. Public Health Service, and a fellow of the Infectious Disease Society of America. So welcome, Agam.

Dr. Agam Rao:
Thank you very much. Okay, I'll go ahead and get started here. So first off, I have no conflicts of interest. The learning objectives for this presentation are to characterize the zoonotic origin of monkeypox and how the infection has changed over time. Also to compare key features of classic monkeypox, which is the monkeypox that occurs, continues to occur, and occurred before this outbreak in parts of Africa, to that occurring during the ongoing outbreak. Outline key questions that remain about monkeypox and explain what listeners should know about monkeypox. I know there's a lot of newspaper articles and other reports about monkeypox, and it might be difficult to wade through all of that, so I hope to simplify all of that a little bit in this presentation.

So, for background information, monkeypox virus is the virus that causes monkeypox. It belongs to the same virus family as Variola virus, which is the virus that caused smallpox before smallpox was eradicated. It's the presumed animal reservoir of monkeypox virus, which, and by reservoir I mean the host in which the virus lives, is small rodents that live in forested regions of Africa. So that's where it constantly lives and survives, despite individual people recovering from illness. The infection itself spreads from animal reservoirs to other animals and to humans, and can spread from humans to humans. The infection was first described in wild caught laboratory monkeys, and the name monkeypox is a misnomer stemming from the fact that it was first identified in monkeys, but monkeys are not the animal reservoir. They are, like humans, beings that can become infected by the reservoir species but are not themselves the reservoir.

The first confirmed human disease was in 1970 in the Democratic Republic of Congo, which at that time was called Zaire. And there are two clades of monkeypox. One is Clade I, which was previously referred to as the Congo Basin clade, and Clade II, which was previously referred to as the West African clade. And going forward, I'm just going to refer to them as Clade I and Clade II. Clade I was historically reported as more severe compared to Clade II.
So I want to provide some information about cases in Africa. I know there's a lot of questions about what is monkeypox? And what did we know about it before the current outbreak? And so hopefully these slides will provide that background information. So monkeypox, infected animals was the main problem, and transmission from infected animals to humans occurs and had occurred before this outbreak, but also person-to-person, to a smaller extent though. What we knew about monkeypox is that respiratory secretions like saliva and skin-to-skin contact with infected bodily fluid, so that includes fluid from the vesicles and pustules that are associated with the rash, but also items that were used by a patient with monkeypox, like shared towels and bedding, could all spread illness. The person-to-person spread, though, was thought to be rare for Clade II in particular. And Clade II is the clade that is associated with the ongoing 2022 multinational monkeypox outbreak.

But in Africa, that classic presentation is easily confused with chickenpox. It can sometimes occur with chickenpox and monkeypox in the same patient. And laboratory testing capacity can be variable in many countries where more monkeypox commonly occurred before this current outbreak. And so we think there was probably some underreporting and misdiagnoses, just because it can be confused with other illnesses, and there isn't necessarily the laboratory testing capacity that there is in the United States at this time.

So, some select work that CDC has performed in Africa before the 2022 outbreak, that might give you a sense for where the focus was and what we knew about monkeypox before this outbreak. So the CDC assisted with enhanced surveillance for human disease, introduction of laboratory diagnostics, whole genome sequencing of virus isolates to try to understand where there might be clustering occurring, and just to try to understand the epidemiology of monkeypox better. Community education, support for outbreak investigations, there were outbreaks before this outbreak that's occurring right now globally, and epidemiology research studies to investigate transmission to humans just to understand the illness, the virus, the infection better.

Clinical studies, including an ongoing vaccine study that involves the JYNNEOS vaccine, which is the the more commonly-used vaccine in the current outbreak response, and assistance to World Health Organization, or WHO, with the development of a monkeypox toolkit that hopefully has facilitated the care and management of patients with monkeypox preceding this outbreak. And finally, the ecology of potential animal reservoir species. So hopefully from this information you can see that we were very involved and continue to be very involved in understanding monkeypox as it occurs in parts of Africa where the reservoir species reside. And the focus was on clinical care, the use of vaccines, understanding what the reservoir is, trying to understand outbreaks, and support countries when they were meeting outbreaks, that sort of thing.

So speaking about the reservoir piece. So the definitive animal reservoir is actually unknown, despite a lot of work that's gone into trying to trap animals and test them and understand this. But multiple studies do suggest a few species of squirrels that I list here, rodents, and shrews as possibly being the reservoir species, perhaps one or all of them. And these photographs just depict some of the animals that CDC ecologists have tested for monkeypox virus, and some of them include potential reservoirs for monkeypox, because monkeypox virus was detected in some, but not all, of these.

So the clinical presentation, or the classic presentation, and again, just a reminder, that is the presentation that had been occurring in parts of Africa for many decades and continues to occur. So despite this current outbreak that is slightly different, those cases continue to occur, and I'll explain that a little bit more in subsequent slides. But that classic presentation involves a distinctive rash that can be painful. Patients often have a really high fever, they have swollen lymph nodes, and sometimes they have complications. The patients can have complications from the extensive rash like dehydration, if they have the rash lesions in their eye, they can have eye infections, they can also have scarring of their skin, but rarely was Clade II associated with death. There have been some cases of deaths, but it has been rare. And these photographs show that classic presentation. And again, this is different from what we are seeing with the current outbreak, but there are some features that are similar, and so you'll see that a lot of the same sentiments that are on this slide, I'll repeat when we explain the current ongoing 2022 monkeypox outbreak.

So more background information, cases and outbreaks in Africa have been occurring for decades, really. There have been select outbreaks in animals. Cameroon expected outbreaks in captive chimpanzees in 2016 and 2014, for example. Cote d'Ivoire had monkeypox virus isolation from a sooty mangabey animal in 2012. And there's been documented increase in incidents of human disease in areas of the Democratic Republic of Congo. And in addition to that increase in the number of human cases in the Democratic Republic of Congo, there's also been some sort of change in the epidemiology of monkeypox, and there's been a reemergence of human disease in several countries in Africa that had not seen cases for 30 to 40 years. So Nigeria, Sierra Leone, Liberia, Cameroon, Nigeria, these are all countries where we've seen that reemergence. So there's clearly something that is changing about monkeypox, even before this outbreak occurred. I have here Nigeria circled, because I'm going to talk a little bit more about Nigeria in later slides.

So there was an outbreak in Nigeria that occurred in 2017, but confirmed cases date back to 1971, when there were two cases, 1978, when there was one case. And then there were no cases in humans until an outbreak in September 2017. And that outbreak involved 132 confirmed cases from 17 states in Nigeria. There were seven deaths, even though it was Clade II of the monkeypox virus. Some of those occurred in very severely immunocompromised patients, including people living with HIV, and the information about the reason for the other deaths is not available. And the mean age of people was 29 years, so somewhat mirroring what we're seeing with the current Europe/US outbreak in some ways, in that the population affected were in their twenties and thirties for the most part.

This is the largest outbreak of monkeypox with Clade II that we were aware of before this current 2022 outbreak, and sporadic cases have continued to occur of this classic monkeypox presentation since the 2017 outbreak was recognized. So possible reasons for the increased cases in Nigeria, but also in all those other countries in Africa that I mentioned have seen what appears to be a reemergence, these are proposed reasons. Absence of vaccine-derived immunity, so the smallpox vaccine, since smallpox is an orthopoxvirus similar to monkeypox virus, is believed to provide some protection. But since the smallpox was eradicated in 1980, that vaccine is not being routinely given anymore, and that might explain why we're seeing some of these infections. There's perhaps some environmental changes, including climate change, change in reservoir distribution and dynamics, perhaps. And again, these are all hypotheses that have been proposed by scientists. Increased population sizes and density, movement of people due to unrest or migration, and improvements in disease detection, perhaps resulting in better identification of cases.

So there's a lot of things being proposed about why more cases are being reported, and those span everything from perhaps people are more susceptible, perhaps there's something about our interaction with animals, or changes in settings like deforestation and population sizes and migration of people that perhaps are facilitating infections. And then also just infections in general, just improvement in identifying them, so improvements in laboratory testing, or improvements in surveillance and public health in general. There's a lot of different things that could be contributing to this, we're just not sure about what these are.

And so before this 2022 outbreak, CDC and other international partners like the World Health Organization were really focused on trying to understand monkeypox well, and the increase in cases that were occurring, it was already on our radar. And actually I think it was in 2017 or 2018 that The Washington Post actually followed a CDC team, some of those members are seen in the photograph to the left, along with colleagues from the Republic of Congo, and they were trying to figure out what the reservoir species was. And there's a really nice health science report that you can access to try to understand a little bit more about that work that was being done and that The Washington Post covered.

So cases outside of Africa though, even though certain regions of Africa is where the reservoir is believed to reside, there have been cases outside of Africa. So in 2003, there was a US outbreak. It was the first outbreak, or the first cases, really, that had been reported outside of those forested areas of Africa where we believe the reservoir species resides. The 2003 outbreak was linked to small mammals imported from Ghana. There were 47 cases, they were at multiple states involving the Upper Midwest of the United States. The cause was traced to the spread of monkeypox virus from imported African rodents to pet prairie dogs that were housed with them, and then the people who had contact with those pets.

The infections were often from bites and scratches, involved children and adults, and the infections occurred in people even if they had received that smallpox vaccination as children decades earlier. So perhaps there was waning immunity and the fact that they were developing infection, even though they had been vaccinated, shows that. There were, however, thankfully, very few severe cases and even those cases that seemed severe, that involved people being hospitalized, resolved and those patients ended up doing well.

So I show these photographs here on this slide just to show you that some aspects of the rash are different from the photographs I showed a few slides ago about the classic presentation. But there are still some features that are common. They are firm lesions, they are deep-seated lesions, they are round lesions, perhaps not as disseminated as the lesions that we see with classic monkeypox, but there are some common features. And the middle picture in particular I just wanted to show you because these are very small lesions, very different from what we see with classic monkeypox in Africa, but similar to what we are seeing with the current outbreak. And so these are all, perhaps, along the same continuum, there are features that are similar to each other, and so we really should not be thinking of the current outbreak as something that is just completely out of nowhere, unprecedented, completely unrelated to what we've seen previously. There are many features that are similar, it's just that it's not entirely similar to what we've seen in the past, whether it's the classic monkeypox presentation or the 2003 U.S. outbreak.

So after 2003, the next cases that occurred outside of Africa were imported cases from travelers from Nigeria to various countries. And so you'll remember from a few slides ago that Nigeria experienced a reemergence of cases in 2017, and since then has continued to have cases after that outbreak. There have been travelers from Nigeria who have been diagnosed with monkeypox once they've reached another country. And so there had been four cases in the United Kingdom, one in Singapore, one in Israel, and one in the United States. But very few secondary cases, and by that I meet infections that occur in people who have been exposed to those travelers who are diagnosed with monkeypox. There have been very few secondary cases, meaning very few spread. The spread has been to one healthcare personnel who, perhaps, came into contact with a patient's secretions while caring for a patient and not necessarily wearing the necessary personal protective equipment, and there have been family members who have been exposed to a patient upon returning. But beyond that, there has not been spread, despite these eight imported cases.

Now in early May 2022, all of that changed. So the United Kingdom reported a traveler from Nigeria, then they, later that month, reported an unexplained family cluster involving three cases. And alarm bells went off when that family cluster occurred because that was unusual. We had been hearing about a few imported cases or travelers from Nigeria, but then to hear about this unexplained family cluster, and soon after that to hear about cases among gay, bisexual, and other men who have sex with men, or MSM, four of them, that is when the international community really became alarmed.

And within days, sure enough, cases were identified from many countries worldwide. And you can see here that since then there's just been a lot of questions, a lot of concerns. On this slide you can see, "A dog caught monkeypox. What does it mean for our pets and other species?", "Is monkeypox going to spread in children?", "Monkeypox: What's Going On?", "Will monkeypox be the syphilis of the 21st century?" Just a lot of questions about this infection now that we were seeing another outbreak, and particularly because it was affecting countries that had not previously seen much monkeypox.

So just to outline this timeline a little bit better. So May 16th, the four UK cases among MSM. The very next day, the first U.S. case was identified. Since then, between May 17th and July 23rd, there have been a large increase in global cases, including in many countries where monkeypox does not typically occur. And on July 23rd, the World Health Organization declared the escalating global outbreak as a public health concern of international consequence. A few weeks later, the US declared public health emergency, and on August 9th is when US cases peaked. Since then, up until the present moment, cases have decreased but are still occurring. But the good news is that they are decreasing quite significantly, they are decreasing, which is good news.

This is a snapshot of where we are right now. These are the U.S. and global case count numbers as of yesterday, October 11th, 2022. So the map on the left side of your screen shows the number of cases by states, by grades of blue, I guess. And you can see from the key below that the darkest color blue is where we are seeing the most number of cases. And the map to the right shows the countries that have been affected. So confirmed and probable US cases as of yesterday, 26,778; confirmed worldwide cases, 71,408. And locations that have not historically reported monkeypox are 70,679.

So clinical presentation-wise, that distinctive rash is still there, it just has some unusual features. It is still painful, it is still firm and deep-seated, but these lesions or rash are really small, and in some cases just scattered over someone's body, or perhaps only one of these little lesions are present on somebody's body... And that's still happening. But because it's presenting a little bit more subtly in many of the patients, it's being confused with other illnesses too, like sexually transmitted infections, for example, but also hand, foot and mouth disease, bug bites, other things that can easily be confused with something that looks this way. But I do want to emphasize that it's not completely inconceivable that it would be related to what we've seen with the 2003 US outbreak, with cases in Africa. If you look closely, if you are a subject matter expert in this area, you see that this is similar to those, it's just a little bit more subtle. And we do have serious complications sometimes occurring in this outbreak as they do occur in Africa and as they occurred in 2003 as well. So there are some similar things still happening.

The spread is still person-to-person spread, most commonly skin-to-skin contact with infected bodily fluids. That skin-to-skin contact includes, but it is not limited to, close contact that occurs during sex. I know many of our cases are occurring among men who have sex with men, but it is important to point out that that contact may be related to certain social behaviors, perhaps dancing closely without skin, or perhaps just being affectionate with another partner, and kisses and cuddling. So respiratory secretions like saliva during kissing, touching items that were used by a patient with monkeypox, like perhaps shared towels and bedding or clothing, behaviors in general. So I just want to caution people into thinking that it's due to sex alone. Perhaps there is a component of that, but there is just close, close intimate contact in general that is associated with spread.

More good news though is that there's been no sustained spread in daycare centers, in schools, in jails, in hospitals, all of these places where there was worry that there would be spread. And this is similar to what we know about monkeypox before this outbreak. There wasn't a whole lot of spread beyond people who had very close contact, beyond household contacts. It just so happens that it's a much, much larger number of people right now. But we do need to understand that better. We need to understand why is it exploding across the country, the world, really, the way it has been? But good news, at least, is that it is not spreading the way COVID does to daycare centers, schools, occupations, jails, hospitals.

The diagnosis is through clinical evaluation and testing of swabs from the rash, and there's widespread testing availability in the United States, so some of the challenges associated with diagnosis in Africa are not there at this time.

So why is monkeypox occurring mostly among MSM? And this is a really complicated question, I would point you towards this publication that is referenced on the bottom of the screen if you want to see what some experts think about this. But overall, I'll just say that infectious diseases occur at different rates because of social, economic, and environmental factors. Pathogens do not intentionally discriminate based on identity such as race, gender, or sexual orientation. Outbreaks enter social networks and propagate based on the characteristics of the pathogen, the host, and the way people in the initial affected network live, work, travel, or play. So more needs to be done to understand this, but I suppose it's not entirely a surprise that certain networks would be affected by certain infections at certain times in history. That doesn't rule out the fact that other networks may become infected in the future, and that is why we're so focused on trying to understand this infection better and treat people, vaccinate people who might be at risk for acquiring infection.

So as far as genomic surveillance, I know there's a lot of information on the screen, I just want to point out that there have been, and this has been reported publicly by CDC quite a lot a few months ago, US monkeypox virus sequences during this outbreak fall into two lineages that are outlined in red and in blue in this slide. And most of the cases in the United States and globally belong to the lineage B.1, which is in red here, but there is another lineage. And all of this suggests that perhaps there were multiple virus introductions into the world. So perhaps there were travelers from Nigeria, or other people that were infected, that were not necessarily identified or diagnosed because the illness can be so subtle, and for many patients only lasts for a short period of time. And at some point it, perhaps, entered communities, and perhaps that is what we're seeing right now. I can't say that definitively, all I can say is that there are what appears to be two clusters, two lineages, and that suggests that there were multiple introductions.

So as far as prevention and treatment goes, there's a lot of information on the CDC website about this, and so I would highly recommend any listeners who are interested in learning more to access that website. There's information being updated on a regular basis. Prevention strategies include general best practices like hand washing, vaccine is available for persons at risk for developing monkeypox and those who have been exposed to someone with monkeypox. And for many patients, pain control is absolutely essential. There is some information on the CDC website about pain control, but if a patient has infection beyond that, for example, really weakened immune systems and really concerning illness complications, they're hospitalized, they're in the intensive care unit, for example, because they have really weakened immune systems, there are other treatments that exist for those severe infections, and CDC can be consulted by clinicians and by health departments, we are trying to get the word out about what those situations would be, and what we consider severe infections.

And so, similar to where we left off with outbreaks, with just monkeypox in general before the 2022 cases, we're still searching for answers. We're still trying to understand how or why monkeypox went from a disease primarily acquired from animals to one primarily spread human-to-human, why it suddenly spread so explosively across the globe, whether cases can be eliminated entirely. It is great news that we are seeing a drop in case counts, a significant drop, which is really fantastic, but we're still searching for answers on whether cases can be eliminated entirely, and also what mitigation strategies might be most effective. And so we are investigating all of this, we're working really hard to try to get answers to these questions as well as we can.

Now, I know this is a whole lot of information, and so I wanted to whittle down to what I hope listeners will take away from all of this. So increased awareness is key. It's really great to see that there are people interested in this topic and attending this meeting, increased awareness is really important. We are one world, in the end, so infections in one part of the world can spread to another, and that is not something that is new. I know people know from the COVID experience that that can happen, from Ebola experience, from a lot of other infections that have occurred, that occur in one part of the world but can easily spread to another part of the world.

Monkeypox, though, does not spread to people as easily as COVID. I fully recognize, yes, it's affecting some networks very severely right now and we're trying to get a handle on it, we're trying to decrease those case counts, trying to get the word out about prevention, treatment, vaccines. But I guess I don't want people to be so crazy alarmed that they're living in fear. It's just really important to wash your hands in general, not just because of this virus, but in general, because of so many viruses and infections that circulate. This is not COVID though, so just want to ensure that that is contextualized, that people understand the risk.

Contact your healthcare provider, that's really important, if you were exposed to someone with monkeypox or believe you might have monkeypox, you should contact your healthcare provider. Consider getting vaccinated if you have risk factors for monkeypox, we recommend that. And as I mentioned earlier, there is a lot of information on the CDC website, it's about self care, about monitoring, about reporting an illness to others, contact tracing, just all of that is really important to trying to get a handle on this infection, minimizing people's illnesses, minimizing spread. And we need that partnership, I guess. Public health authorities need that partnership with the effected communities and the public in general to ensure that we get a good handle on this infection in general.

So with that, I will end this presentation and just remind you again that there is a lot of information on the CDC website, and many of your questions might actually be answered by content that is already there at www.cdc.gov/monkeypox. And I'll turn it over back to Ashley.

Ashley Peery:
Wow, thanks Agam. We do have some burning questions coming in from the audience, so if it's all right with you, I vote we dig into those. So our first question is coming from Noa, and this question is asking about monkeypox in animals. Noa would like to know in the situation with the pet prairie dogs, were all of those animals infected at the same time, or I think their question is, was there some retention of the virus and perhaps reactivation? Maybe like a latency reactivation situation, and could that virus stay in the body forever? So that's kind of a complex one to unpack, but what do you got?

Dr. Agam Rao:
I think I understand the question. If I'm understanding correctly, the question might be whether, similar to chickenpox reactivation resulting in zoster years and years down the road after someone has already had chickenpox, can something like that happen with monkeypox? And the answer is no, we are not aware of that happening. If it happens, it's going to be a new phenomenon, but we don't believe that that happens with monkeypox. In the case of these prairie dogs, they were housed in the same space as some rodents that had been in Ghana, and we think that that's how those prairie dogs became infected and then they became pets. Now there is a time period, like a lot of infections, what we call an incubation period, from when someone gets exposed, or when an animal or a person gets exposed, to when they actually develop illness. And so there is that incubation period for monkeypox that can be as long as 21 days. And that is what happened in this situation, where these prairie dogs became visibly ill a certain period of time after they had been exposed.

Ashley Peery:
Thanks for unpacking that one for us, and a very interesting question, Noa. The next question is from Alexander, and it is also related to animals. Alexander is curious if there have been any U.S. monkeypox infections identified in animals so far this year?

Dr. Agam Rao:
Yeah, I think we're investigating this. There's nothing to report from the U.S. right now. There was a report internationally, a report or two internationally, and some questions raised about some of the testing associated with that, and whether those were false positives or not, or whether one of them [inaudible 00:34:36] two out of... There's still some uncertainty there. The reassuring thing I want to convey is that there have been a lot of cases in the United States, and despite some CDC teams trying to evaluate whether some pets have had monkeypox, we're really not seeing a signal there. So it's possible we might see a case or two or three here and there, but we are not seeing any sort of signal. And yeah, that's good news, we're not seeing our pets, our lovely little pets, I have my own pet that I'd be very concerned about as well, we're not seeing them infected on any large scale.

Ashley Peery:
That is good news. So, the next question is actually a combination of two similar questions from Alexander and from Paul. So Paul says, "What are the possible reasons for the initial rapid spread?" And Alexander asks, "You did note that overall cases are going down, which is fabulous news, but are there any states or regions that are still seeing accelerating monkeypox cases currently?"

Dr. Agam Rao:
We do have information on our CDC website about specific states. I believe that, overall, we are decreasing, but I don't think that I can say whether there are any states that might be increasing. I think not? But perhaps looking at the website, we have information on a state-by-state basis of the number of cases that are occurring, and you can take a look at that. I think our general sense is that case counts are decreasing, that prevention strategies are working, vaccinations are working, and this is something that we're seeing worldwide, so it's not just in the United States where this is being observed, the drop in cases.

I do want to caution though that yeah, it's wonderful that we're seeing cases drop, but we are seeing severe infections in some people. So if someone has a really weakened immune system, just like any other infection, including COVID, you can have a more severe infection with monkeypox. And we are seeing people who have really weakened immune systems, for example, advanced HIV for example, but before this outbreak we also saw it in people with really severe cancer, they can get very, very, very sick with monkeypox. And so despite the fact that the case counts are dropping, I just want to say that we are seeing severe infections and people with weakened immune systems are the ones most affected by those severe infections, and we do need to stay alert.

Ashley Peery:
And to kind of circle back to Paul's part of the question, are there any possible reasons that explain that initial really rapid spread? Was that just detection bias? We were looking for it and so we found it?

Dr. Agam Rao:
I think we're still investigating this, but what I can say is that a lot of people around the world, not just at CDC but at other parts of the world, are looking into whether or not monkeypox was circulating for months and perhaps was undetected. We're not seeing evidence of that. We were trying to evaluate stored samples from patients. I know the United Kingdom has looked into it and felt that perhaps their earliest case was sometime in April based on that. It's possible that it was circulating for a couple months before the rest of the world recognized it? Sometime in middle of May or late May is when a lot of the countries first started seeing cases and only after the United Kingdom raised the alarm. But I don't think that this has been going on for too terribly long before that.

Our initial cases in the United States seem to trace back to some large events in other countries. The Cayman Islands for example, and various other large Pride events, for example, where people were in close quarters and interacting very closely with each other, that's where our initial cases in the United States trace back to. And so we don't think that cases were occurring, certainly not for months and months before that. But still, we are still continuing to investigate. We want to make sure that when we say something about this, that it's truly well informed by as much of a investigation, as thorough of an investigation, as possible.

Ashley Peery:
Wonderful. Let's switch now to a couple of questions related to the vaccines. Alice is curious, what do we know about the real-world effectiveness of those vaccines? You kind of alluded that they might be part of the reason why we're seeing this slowing in our case counts. Do we have any of the data that you can share about how effective the vaccines are at preventing infection or severe illness?

Dr. Agam Rao:
Yeah, so there was a publication in CDC's MMWR. So that is a publication that comes out weekly by the CDC. MMWR stands for Morbidity and Mortality Weekly Report, and you can Google it to find it. There was a report, I think it was the very beginning of this month or perhaps it was the end of September, but it was a report about the vaccine effectiveness, the real-world vaccine effectiveness that we're seeing so far. And the reports suggest that even a single dose of the two-dose JYNNEOS vaccine series might be having an impact on preventing infections. And you can look at that paper to see some of the details. There are a lot more vaccine effectiveness studies underway, and we're hoping to be able to come out with those results in the next few months. But that first report seemed pretty reassuring, I guess, that the vaccine is effective.

Ashley Peery:
So more good news. And Alice is also... She's hoping you can reiterate who are folks that should consider getting this vaccine?

Dr. Agam Rao:
That too is something that is being discussed more. But at this time the US government recommends that a vaccine be given to those who may have had contact or definitely had contact, very close, intimate contact, as we're referring to, or household contact, to someone who may have had monkeypox or was confirmed to have had monkeypox. But in addition to that, when we're talking about people who might be at risk for developing monkeypox, the US government has also provided some recommendations that were widely, I guess, reported out, I believe it was either last week or the week before. It included people, predominantly men who have sex with men, who have been diagnosed with, for example, a sexually transmitted infection within the last six months, who have more than one sexual partner. There's a couple different things related to men who have sex with men in particular that have come out.
As far as people beyond that, the Advisory Committee on Immunization Practices, or ACIP, is the group that provides federal guidelines about vaccine use, and you all may have heard of the ACIP and their role in COVID vaccine guidance. They are assembling, actually, to consider who the monkeypox vaccine should be expanded to. So within the next few months, perhaps... By the end of this calendar year we're hoping to have more information about who the vaccine should go out to beyond what is already stated, and beyond what is on state health department websites, beyond what is on the CDC website.

Ashley Peery:
So more to come on that, Alice. Our next question is from Laura. Laura asks, "Have we found any genetic mutations in these strains that have been spreading currently versus the older strains?"

Dr. Agam Rao:
No, actually we have not seen anything terribly concerning. We have seen little things like deletions and small mutations that are expected, but not anything that would suggest that these viruses are actually completely different from what has been reported in Africa, for example, during the classic presentation of monkeypox. So that's another point that I should mention. In the picture that I showed of the clusters of monkeypox, in the at least two introductions that have occurred, there's clustering of the virus that is being isolated worldwide as part of this outbreak with previous strains. And so we aren't seeing resistance, for example, to tecovirimat, which is one of the treatments for monkeypox. We are not yet seeing those concerning things, but we are on the alert for them because we have concern that there could be a low threshold for resistance developing for mutations occurring. Those have not yet been observed, and we are routinely performing genome sequencing to ensure that if there is any such mutation, that it is identified.

Ashley Peery:
So another question, it's again related to variants, Frederick is curious if the different variants of the virus, perhaps those two clades, have different presentations?

Dr. Agam Rao:
Yes.

Ashley Peery:
Do they look different in the clinic?

Dr. Agam Rao:
Yeah, so Clade I and Clade II, there are two clades. Clade II is the one that is, the only one, that is implicated in these cases that we are seeing as part of this global outbreak. But Clade I... I'm sorry, I hope I said this right, Clade II is what we're seeing with the current outbreak. Clade I and Clade II occur in Africa, after exposure to certain animals and person-to-person spread. Clade I, historically, has been the one involving the more severe presentation. Not to say that what we're seeing in a lot of patients is not severe, and pain is absolutely severe. So what I mean is more like extensive lesions, large lesions, dehydration, more likelihood to have complications. Yeah, that's what I mean when I say more severe infection. I'm not referring to the pain, I know that the pain is severe, regardless of whether it's Clade I or Clade II.

So the clinical presentation can be a little different between Clade I and Clade II in terms of that severity I just explained. As far as other differences, I think that's also something that really is a research gap, or a gap in our understanding, that needs to be understood better. Clade II is the only clade involved in the current outbreak, outside of Africa.

Ashley Peery:
Great question, Frederick. So our next question is from George. George is curious if the ongoing sporadic cases that were occurring in Nigeria, maybe they could have served as an early warning for the world. So he has a big question. He says, "What would it take to get to an early warning system for infectious diseases?"

Dr. Agam Rao:
Yeah, I think that's a really great question. And I think all of us at at CDC and the World Health Organization are always focused on what's going on internationally, because we are an interconnected world, and anything that's happening on one part of the world, it affects us all. We are one community and one health. Animals, animals being a source of infections, this is something that we all feel very strongly about and that's the reason that we work in these areas, of so-called rare pathogens, that end up becoming all these large problems.

And a part of the problem is funding. And I know people hate to hear that, that funding is a problem, but it's true. It's that we could do more if we all had more funding, if there was more of a focus on things that were happening in other parts of the world, if we could establish things like an early surveillance system. We all were aware of the cases in Nigeria, and there was a CDC team that went out to help with those cases and try to support the Nigerian government as they were leading the investigations. But even before Nigeria, if you'll remember from my slides, we've noticed a reemergence in various parts of Africa. It's a question mark; why this is happening? Global warming? More interaction with animals? Or urban deforestation? All of these might be contributing, and it's just a reminder that it's a domino effect. It's not necessarily one thing that results in these outbreaks, it's a lot of things happening over a long period of time. And an early warning system sounds great to us if we could establish something.

Ashley Peery:
So your answer was actually a perfect segue for a question from Alice. She says, "As human populations increase and climate change continues, can we expect more viruses to cross from animals to humans?"

Dr. Agam Rao:
I'm an expert in poxviruses, so I guess I should not be commenting on what I think, personally, about other infections. I think yes, for poxviruses, yes, that is our concern and that may have been what happened here. So it's something to think about, it's something that requires a lot more experts in different fields to think about as well. And I know they are thinking about it, too.

Ashley Peery:
Thanks for that. So our next question is coming from Sam. And Sam, we're going to kick back to animal reservoirs. So Sam says, "The rodent reservoirs, they play a role in maintaining the virus in Africa. Could we see this virus move into rodents or other animals in countries outside of Africa? And what does that mean for our ability to stop this outbreak?"

Dr. Agam Rao:
Yeah, that's a very good question, and that is part of the reason that we have CDC folks who are going out to try to swab animals, pets to understand whether or not infection is spreading to our pets, to our animals. So, could it? Yes, it could. The animals that we think are the reservoir in Africa are small rodents, like squirrels, that could perhaps get infected in the United States. The exact animals probably don't exist in the United States, but related ones probably do, and so could it? Yes, it could. Have we seen it so far? No, but that is indeed a concern. Whenever you have a virus that involves an animal reservoir, it becomes harder to eradicate, much harder.

One of the reasons smallpox could be eradicated is that it was spread within people. We didn't have this reservoir of animals to worry about. And so eradication, although extremely, extremely difficult, and I know there's been many papers, many books, many things written about how amazing that entire eradication campaign was, and it really was amazing. Something like that, even something like that, would perhaps not eradicate monkeypox from the world, because of the animal reservoirs in Africa and the potential for that to spread to other countries. But I want to say that has not happened yet. So, could it? Yes. Has not yet.

Ashley Peery:
Thanks for that reiteration. And actually what you said, contextualizing monkeypox versus smallpox, you have animal reservoirs for monkeypox; for smallpox, you didn't, actually shook a question loose from me, if I can ask a question. Was smallpox, once upon a time, zoonotic and it became more specialized for human hosts? Is that something we know?

Dr. Agam Rao:
No, variola virus, which causes smallpox, was in people. It was spreading via people. It's not in water, it's not in food, it's not in soil, it's not in... So it was spread through people, and ring vaccinations, which is the type of vaccinations ... Managing the infection in people was the focus, and the reason it was eradicated.

Ashley Peery:
So one question. There's a question that came in asking about the lingering effects of smallpox ... Or, sorry, not smallpox, monkeypox virus. These patients who recover, do they have any lingering effects or health issues that they might still be dealing with?

Dr. Agam Rao:
Yeah, it's a good question, especially coming off of all of the concerns related to COVID and long COVID. We're looking into this, we're not aware of this being anything like COVID, for example. But it is something, as we move into a different phase of this response, that we want to understand better, just like, "What have been the long-term sequelae, if any, in patients?" And that information is going to come with time, just as more time elapses from when someone had an infection. Yeah, as more time elapses, we'll have a better understanding of that.

At this time, other than perhaps scarring, unless someone had really severe infection, which of course, like I said, is happening, and they had severe infection and resulted in the need to have a surgical intervention, for example, because they had an infection of their skin rash, unless they had those sorts of complications... And rash in their eye, for example, through touching their eyes or something and resulting in some eye problems, visual problems, we're not aware of any other concerns that someone who had a milder illness is having. But we certainly want to investigate that, evaluate that. It's going to take some time before we have a good picture of that.

Ashley Peery:
Thank you. And as a reminder to the audience, we do have a few minutes left, so if you've got a question that you've been thinking about putting into the chat, go ahead and put it in. I've enjoyed this conversation so far, thanks, Dr. Rao. I do have a question coming in from Tom. And Tom is curious if you want to comment on any parallels or differences in the HIV/AIDS epidemic response, which also affects men who have sex with men, and this response. Are there any lessons learned, perhaps, from HIV/AIDS that have perhaps helped in this response?

Dr. Agam Rao:
Well, I think CDC has a lot of experts in HIV, in HIV science, in messaging, in surveys of affected communities to understand the acceptability of various prevention strategies. So that all has been incredibly helpful. And some of the things that we've used in this response, so we've had focus groups, for example, trying to elicit information from affected communities to understand what barriers there might be to, for example, vaccination, so that we can work on, perhaps, messaging to clarify or to reassure people, or... Working with the affected community is critical to the success of any public health work. And so I think the work that has been done by public health experts in HIV has been leveraged very much so during this response. But it is not just people with HIV that are affected by this monkeypox outbreak, and so it's not just the work of HIV experts, it's also a lot of other public health work that has facilitated this response.

Ashley Peery:
All right. We have a question from Sabrina. Sabrina is curious if the CDC is working on an over-the-counter rapid test for monkeypox to increase testing capacity?

Dr. Agam Rao:
Yeah, I'm not a laboratory expert, so I don't feel like I'm in a position to answer that correctly. I'll just say that what I've learned, from my laboratory colleagues, is that the laboratory test is pretty complicated. It's a very sensitive test, which is partly why we were seeing false positives at various times in this outbreak response, and it led to a lot of stress by people who had no exposure, children, pregnant women, other people who had no reason to have monkeypox, had an unusual appearing rash, it was tested, it ended up being positive, it turned out to be a false positive because the test is just so sensitive that it picked up a little bit of contaminant from the laboratory well next to it.

So I am not an expert in any of this laboratory work, and so I'd have to defer to my laboratory colleagues. What I've understood from it is that it's complicated. And there is currently, I hope, just through introduction to commercial laboratories and the increased capacity at the state laboratories, that anyone who needs to get a test is getting a test. And that is my hope. I think that's the reason that the introduction to commercial venues happened. [inaudible 00:56:35].

Ashley Peery:
So thanks for that. We actually have a comment here from Dakira. She says, "Thank you for sharing your knowledge. Your presentation was clear, concise, and super easy to understand. So thank you for sharing." We'll take one last question actually. We're going to take a question from Frederick, who says, "Women and monkeypox, will they be included in vaccine plans soon?"

Dr. Agam Rao:
The Advisory Committee on Immunization Practices is coming together to discuss all the data, including the epidemiology and who is being affected the most, what sorts of behaviors are associated with the people who are affected the most, who has the most severe infections. All of this is going into their thinking, their discussions, and I think we'll hear soon enough, before the end of this calendar year, who the vaccine should be expanded to. Women comprise a small percentage of the cases that are occurring in the United States and actually worldwide, we do have that information on the CDC website, but that is not to say that they should not be vaccinated. I just want to say that the community is not as affected as certain men who have sex with men. And it'll be up to the ACIP to discuss further.

Ashley Peery:
So more to come on that as well. And that's actually all the time we have, so please join me in thanking our guest, Dr. Agam Rao. I'd also like to give a special thanks to those who made today's program possible. Those are our donors, our volunteers, and viewers like you, and all of our partners who help us reach, educate, and empower millions of people around the world today and every day. So thank you.

Our next "Shared Planet, Shared Health" webinar is going to feature Dr. Amanda Beaudoin. She's going to talk about antimicrobial resistance, and how AMR spreads between people, pets, livestock, and the environment. You can look for the link to register for that webinar in the Q&A. You're also going to see a link for a survey. I hope you'll take a moment to respond, your responses, we do look at them, and they help us improve our webinars so that each time we get better and better, and we know that we're giving you guys the kind of content that you want. So thanks again, and I hope to see you next time.