Infectious disease specialist Dr. Monica Gandhi, MD, MPH, delivers the latest on monkeypox (or MPX), including what to understand about its origins, which patients are at risk, how cases are trending, how to optimize testing accuracy, when to provide “compassionate care” treatment and who should get the vaccine. Plus, hear her thoughts on reclassifying MPX as an STD.
So I'm going to talk about everything monkeypox but we're gonna start with the history of it. So you know the way to think about monkey pox is essentially and and and the W. H. O. Is debating this name. So I'm going to refer to as MPX which I think maybe it's new name. But it's essentially a member of the pox verde family of viruses called Ortho pox virus. And specifically it's a double stranded DNA virus and the subset. So if you think about these three viruses that we hear about a lot SARS cov two is an RNA virus. HIV is a retrovirus. So it goes from RNA into DNA. And then that D. N. A interval it's into your chromosome. And monkeypox specifically is a double stranded DNA virus. It's family only has a few cousins. The Ortho pox virus has three other members of in the fam One is smallpox which was now eradicated um declared eradicated by the World Health Organization as of 1980. The second is vaccine E. A. Which was used to make a smallpox vaccine. And the third was cowpox virus. So these are the three major um cousins in the family of monkeypox. Now, where where was this even described? How did it even get this name? Well, it was first described in 1958 where two outbreaks occurred in monkeys used for research and that's where it actually got its name in no way or monkeys major carriers of the disease which is why um that and that sort of strange stigmatizing aspect of the name is why there's a real attempt to change it. But right now it is called Monkey Pox. It's closely related to smallpox as we talked about. And where did we used to see it before this large outbreak that we're experiencing now? We did used to see it essentially over the last decade. Why over the last decade in Western Central Africa? Because probably the mass smallpox vaccination programs which had been stopped in the late 70s, most everywhere they had worn off. And so we have a generation that's grown up without any smallpox immunity and then started seeing these outbreaks mostly over the last decade in western Central Africa in what are called endemic regions. So this is an absolutely heard of virus we just had never had. It caused such a large outbreak as it did starting on May 4th. And those endemic outbreaks usually were connected to having some connection or touch or a bite of infected animals. So rodents like rat mice and squirrels um or touching animals. And in the us actually we never really saw it except in returning travelers. So in 2021 to returning travelers from Nigeria around a lot of people on the plane, You know did a lot of contact tracing but it's not very easy to pass in that way and there were no context but that's when we saw it in 2021. Just two returning travelers from Nigeria. There was a strange outbreak in the U. S. In 2003 but it was also related to rodents. So what had happened is infected animals and were brought over from Ghana. They got connected to the prairie dog population in the midwest. People bought these pet prairie dogs that were infected with M. P. X. And there was 71 cases of MPX in um in people in the midwest. It was a small outbreak, no human to human transmission. So always thought related to animal exposure prior to this. But in the context of a large outbreak that we're going to talk about next, Nigerian scientists and clinicians have come out and said, you know, we have seen sexual transmission of this virus. It's just that in places where homosexuality is criminalized, we're not going to be publishing or talking about that the Public Health Department but they're actually likely was sexual transmission even prior to this large outbreak, which is mainly being driven bisexual activity. So what about this outbreak? When did it start? And where are we with it? Well, it was called non endemic because it wasn't in western Central africa. It started in the UK Canada Australia. Us. But the first case was reported to the World Health Organization on May 12. So we now have more than 4.5 months worth of data. We really know how this was being spread. The earliest cases were in the UK than the rest of Europe. And then in um it was sort of linked to raves in Spain and Belgium And it went to many countries, 118 countries, but the places where it first started is where the cases have come down the most dramatically. So that would be UK. And Europe. And now here in the us and we'll talk about it as well. In terms of this epidemiology, it is overwhelmingly among gay and bisexual men, 98-99% of the cases are in men. And this top curve that shows you this this what age groups that's occurring in men really looks like a very typical curve for sexually transmitted disease. That's mostly being spread in gay men in the gay male community. It does seem to be from sexual contact. And I'll talk about that more. We used to say maybe skin to skin, close respiratory contact, but the majority of transmission I think is actually sexually transmission. And and again we'll talk about that the U. S. Is now leading the world in cases then brazil is next and then spain and France. But we are seeing decreases in most areas of the world, except there's still some increases. Unfortunately in some countries in latin America like Colombia, the cases have absolutely been slowing in where it first started Rarely. There can be transmission from close contact, even if the majority is actually spread. There is rare transmission from close contact. There are 31 cases in Children probably from parents having the lesions and then cuddling or hugging the Children. Um and there have been overall in this 65,000 person outbreak, 20 deaths total, it doesn't have a very high mortality. There are actually two clade in endemic in endemic regions and there's what's called played one which used to be called the Congo Basin clade. And now and those played too, which is what used to be called the West Africa played. And this is seems to be the West Africa played a lower mortality rate. But there have been 20 deaths, 11 of those have been in Africa and the remaining nine. Um I show you here and one of them was in a severely immuno compromised adult male in Los Angeles. So in terms of the US outbreak, 25,341 cases and New York used to be leading the country in cases, but the cases have come down very significantly in New York and now California is leading the country in cases, but more in southern California and Los Angeles. The cases have come down here in the bay area and in San Francisco significantly. And when we turn to and then we'll definitely will stop any time and ask questions because I'll talk a little bit about other infectious diseases as well. But in terms of the symptoms of this infection, it really does. This is one of the largest case series which was published in the new England journal in july of 528 cases in 16 countries, 98% gay bisexual men at that time, 75% white, 41% had HIV And skin lesions was really the most common symptom, most commonly. These skin lesions were in anatomical areas of sexual spread, anal or genital lesions, and they can be very painful, singular or multiple, ranging from flat all the way up to blisters. And I'll show you a picture in a minute. There were mouth lesions which are also very painful and 5% And and systemic symptoms occurred in about 60% of people. So that was um some fever, big lymph nodes, lethargy muscle aches. And there was no distinction in this smaller case series between symptoms with those living with HIV or not. And these are an example of some of the lesions. You can see that they're not always in the same stage of progression, but they can go from flat to the more blisters to the particular lesions and then crusting and once they've crusted, they are no longer infectious. So, in terms of the larger case series, because the CDC has now published a larger case series, this was published in the mmwr on august 12 and this was 2891 cases, um 99% men. Again, 94% of those who would be interviewed reported the same sex activity, 41% White. And there has been an absolute change in the demographics in this country for more of white gay men to now as the latest data. Much more burden in uh in Latino and black gay men. And so it's important to to in terms of vaccine equity um, to to ensure that we get out to those communities, the vaccine. Um, 41% of people also had HIV. That's it's it's very unusual for them both to have the exact same percentage of HIV. Um and it's also unusual in the sense that 41% of gay men obviously do not have HIV. So it's it seems that there's an interaction or an enrichment somehow in the monkey pox. In cases of monkeypox, of those who have HIV, this is the first time we've ever seen HIV and an Ortho pox virus temporally overlapped. Remember smallpox pretty much gone by 1979. 1st case reports of HIV 1981. So we don't really know the interaction between Ortho pox viruses and HIV before this. And maybe there is some propensity in the state of HIV to get Ortho pox viruses. 42% without pro drome and this in this case, 46% genital lesions. And then another follow up report in the mmwr looked a little bit more about well, in that same series. How many other stds were there. And this was an important study because of those in this. There was 1979 cases in this um in this evaluation was a subset of that 28 91 and there was higher rates of HIV. 38% but also high rates of other stds 41%. So syphilis herpes these are comedy a gonorrhea but herpes and syphilis can of course do present with ulcers often singular. So it's very important to screen for more than one STD. If you're screening for monkeypox and in this particular case series they were able to take a closer look to see well any difference in the symptoms between those who had HIV and those who didn't and actually those who had HIV there seemed to be more rectal symptoms more tin, isthmus, more bleeding. Um rectal bleeding more prevalent or bloody stools more practice. They didn't comment if there are more anal lesions but there seem to be more symptoms in that area. And so that so far seems to be the most distinguishing look. And I certainly think that anyone with HIV should be targeted for the vaccine. So I wrote a position piece with other kind of STD experts that I think at some point we have to just decide if we call this a sexually transmitted disease. We we we are position statement says that that we do think it should be called an S. T. D. And the reason to do that as it helps target your resources. But importantly remember that there are other stds that can rarely spread by other means her peace. For example we all learned in medical school about Herpetic Whitlow which is the legion that you can get on your finger. If you touch a herpes lesion that's not sexually spread. But you can get it from touching the lesion prior to universal gloving during general exams by health care workers. Health care workers would get syphilitic lesions on their hands when they examine general syphilitic lesions and moleskin contagious. Um Also could spread from contact and not sexual transmission. But if the majority of the spread is sexually transmitted like in herpes syphilis um then I think it should be called an S. T. D. And I think there's there's good reasons to do that. But it has not been labeled as such. Another sort of major piece of evidence of why it's really sexually spread mostly and again not all but mostly is that swab in this study in your surveillance swabbing urethral or anal swabs. Um You could see viable virus in those swabs. So um not only is it viable in the semen but just even in the anal canal which likely indicates that it's viable viruses is spread from person to person through anal sex. So our next turn to the vaccine because the vaccine you know was really the vaccine for smallpox because we hadn't had designated vaccine for monkeypox but they're close enough related. And how do we know that the smallpox vaccine A. K. M. 2000 or the genius vaccine which is the one we prefer because it has fewer side effects. How do we know that it works against monkeypox? Mainly because the temporal relationship that we only started seeing monkey pox pandemic outbreaks in western Central Africa once smallpox mass smallpox vaccination program ceased and had worn off and I think that's really important. And so um and so beyond that there was a small study from the DRC which I'll show you in the next slide that indicates that there's about 85% protective efficacy against MPX with a smallpox vaccine. You heard from the Biden administration on August 8 to give the vaccine because we have less doses fewer doses of vaccine than we needed by then. Um to give it into germ aly and the reason for that strategy is if you give it subcutaneous Lee you need a higher amount actually. Um and intradermal administration of vaccine which hasn't been studied Virginia. So I want to be clear with that. It's been studied for other vaccines, other um commonly used vaccines. Um But intradermal administration the reason you can use a lower dose if you put it right into the skin raising a blub like PPD is because um there's a lot of energy in presenting cells there in the in the in the in the surface of the skin. And so that is the current method that has been endorsed by the California DPH to give the vaccine while we're waiting for more vaccine supply. Um, and in one vial of 10.5 mills, you can get almost five doses of 50.1 mils with intradermal administration. Again, the main most convincing evidence that we know it works is we only saw this problem once smallpox vaccination programs ended. This is a P N. A. S paper that models that, but this is also a small paper from what was called at the time that is D. R. C. Uh Democratic Republic of Congo in 1988 88. That estimated about 85% effectiveness of the smallpox vaccine against MPX. And we've certainly seen success. And what does that mean? Well, we've seen decreases in cases worldwide from the MPX outbreaks starting around the third week of august um, these cases have been very steadily declining both worldwide and in the United States. And this is the map here on the left, the United States, the one on the right is the worldwide outbreak and essentially, dr Tedros from the, the director of the World Health Organization is postulating that will likely be able to eliminate this virus from US UK europe. Um, latin America places essentially where it's not in the animal Reservoir, which it does not seem to have gotten into. Um, and that's great news, but that also means that places where it's endemic, where it is in the animal reservoir where it is in rodents will need the vaccine to and as the vaccine has been rolling out unfortunately. And very maybe predictably if we looked at what happened with the history of HIV and HIV treatment access Western Central Africa have not been given an offer doses of the vaccine. So here in the us over 680,000 doses have been administered. You can see as of the latest that we have started administering the second dose which it is a two dose vaccine administration 28 days between doses or can go longer. And in terms of how many people need it, if we just look at the US I think everyone who qualifies for prep for pre exposure prophylaxis. I wouldn't just include men that would include anyone with multiple sexual partners. And that's about 1.2 million individuals. They probably all should get the MPX vaccine. And then if you had 1.2 million and you times that by two, That's the number of people who qualify for prep you needed. And then at least the 648,500 gay or bisexual men who are living with HIV should get the monkey pox vaccine. Um and that's an additional set of doses. So I think about 3.7 million doses should be given out in the us. And again we're at about 650,000. So we're making progress but we still have a large population to vaccinate. And I think the HHS has really made a lot of movement in getting more vaccinations to um uh the U. S. Population. They made a deal with the genius vaccine company which is called the Bavarian nordic company to deliver more vials of actually that we can make 2.5 million doses of genius here in the United States. Um which I think is going to make our vaccine supply up to 5.5 million by the end of the year. One thing I want to add on testing and then we'll go to treatment and then I'd love to hear your questions. Then we can talk about polio and measles if we want. Which is that very rarely. Just very rarely when the way you test is you should take two swabs if you can from one lesion rarely. Um it's a PcR test and there has been some cases in California where there's a deletion in the in the primer essentially used for the Pcr in the part of the virus that that is being amplified in the tumor necrosis factor receptor gene. And if that deletion occurs, the PcR will artificially look negative even if they have M. P. X. So if you really think they have MPX please report that to the California DPH and they will run a different ways so that we can see if it's these one of these rare false negatives. Again it's very rare. But I wanted to make you aware and then I will just end with treatment because I told you about the vaccines were getting out. The vaccine cases are going down all that's getting better. But but there is a treatment and and this really should be used for anyone who needs it on compassionate use. And what I mean by that is there are some people um, uh, that fundamentally um, in treatment who have so much pain or multiple lesions that we need to get them treatment. And what is this treatment it's called? Tech over matt, What is this? It's an antiviral. How do we know that it works in MPX? We don't actually, it's just that it was, it works in smallpox. And how do we know that? Well, it was approved under what's called the animal role in 2018. And what that means is that actually the military is still being vaccinated for smallpox even though it's been eradicated in the case of a bioterror event. And because of that, there are some rare cases from the vaccine, because both of these vaccines are live of eczema vaccine. Autumn where there can be essentially a um reaction that looks like smallpox. Um, and so there has been some treatment of eczema vaccine Autumn with um, take vera matt. And those cases have resolved and beyond that there's nonhuman primate data. Um, that looks like take over matt works against smallpox put putting that all together. Take over matt is actually approved for smallpox. And so as I told you case reports you know even since it's been eradicated in in in vaccine related um uh conversion that it does work for that. And how do we know that it anything about mps? Well there was a study published in Lancet I. D. This year in the setting of this large outbreak that there were seven people who were in the U. K. And they got take over man and they all got better. Sorry actually they all got something else but we're not using this. Three of them got something else but one of them got takeover matt. They got better. Kind of hard to tell right because they are natural history is you're going to get better um But shorter viral shedding than than those who didn't get take over matt. And then the largest case series of people that I told you about. One of the largest case series in the New England journal. Of those 528 individuals where we talked about the symptoms. Um 2% had gotten tech over matt. They didn't really say much about those individuals. They just said quote they got better again that's the natural history. So we don't really know. And then there is a case series published just two weeks ago in the C. D. C. 549 patients here in the US who got take over matt from May to august. And in this case um they did get take over matt and uh and they got better. Again we're not it's not a great comparison but there's a lot of hints a lot of anecdotal evidence that people do get better. We can't really compare it against people who didn't get taken care of at unless we did do a randomized control trial and that's what's going to happen. At least it showed it was safe. So what do I mean by a randomized controlled trial? Well there is one start that that just started actually by the way don't put them in the randomized controlled trial. If they have very sensitive lesions high risk sites severe fair and rectal pain, lots of lesions rapidly progressive lesions. You know something where they need to be hospitalized. Go ahead and ask for the compassionate use of tech over matt from the C. D. C. You have to fill out some paperwork but it's absolutely worth it. But there is a trial that just started and that's really because we have some degree of equipoise if it really works and doing a randomized control trials. The best way to tell against placebo. And so we do symptomatic treatment. If people get sick we give them take over matt if people get sick we do sits past we do gabapentin tin sometimes opiates. It's it was a very we had a high number of cases at ward 86 in July. But what about this clinical trial and why are we doing it? It really is to ensure that we don't get resistance to the drug to really compare against placebo. And essentially it will allow first in the U. A. And then marketing um or sort of a full stage approval. And so um and so what does this clinical trial look like? It's called the stomp study or the E. C. T. G. A. 5418 study. And it really is randomizing people to getting take over matt or not. Um uh It can involve Children. You can absolutely enroll Children, pregnant women. Um And again those who are not eligible for randomization or those with very severe disease. And um the schedule of evaluations is just watching people on their placebo are on the take over matt. So giving it um uh different arms, anyone can be rolled over into tech over matt and arm. See and why. One other reason that we want to do it and I'll just end with this is why we would even think about the concern of resistance. We don't think that there's any takeover amount resistance out there. But the way the takeover amount works is it binds to what's called the V. P. 37 protein which is used by orthopedics Ortho pox viruses to aggregate. And um importantly it looks like just and this is in cell culture but it looks like there would only need to be one mutation to get resistance to take over matt in the V. P. 37 coding pathway and that makes people nervous about using it in sort of a widespread way. And so we have the C. D. C. S. Said let's use it more judiciously and try to use it in the context of a clinical trial. And so we have a we are one of those sites at 1 86. If you have any one you'd like to randomize um or you'd like to enroll in this trial. Um So in conclusion this is not actually a new infection. It's been going on in Western Central Africa. They will need global vaccine and therapeutic equity um to totally contain this. I leave you with this intriguing questions we reclassified as an STD. I think we should, vaccines do seem to be working and we have a new trial going on for therapeutics.
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