Clade I Mpox Response

Mati Hlatshwayo Davis: [00:00:13] Hello everyone, and welcome to this episode of Let's Talk ID my name is Dr. Mati Hlatshwayo Davis, and I am thrilled to bring to you an episode that I believe is a very high consequence, as we talk about the clade 1 M-pox response. I'm joined today by two wonderful guests, Dr. Jennifer McQuiston, the principal deputy of CDC's Division of High Consequence Pathogens and Pathology, and incident manager of the 2024 clade one M-pox response. Welcome, Doctor McQuiston.

Jennifer McQuiston: [00:00:46] Thanks for having me.

Mati Hlatshwayo Davis: [00:00:47] And I'm also joined by Doctor Agam Rao, medical officer in CDC's poxvirus and rabies branch and Chief Medical Officer of the clade one M-pox response. Thank you so much for joining us.

Agam Rao: [00:00:59] Thank you.

Mati Hlatshwayo Davis: [00:01:00] So in early December of last year, the CDC issued a Health Alert Network advisory for clinicians and public health officials regarding a concerning m-pox outbreak in the Democratic Republic of Congo. What do you believe clinicians need to know about the DRC outbreak? And I'll start with you first, Dr. McQuiston.

Jennifer McQuiston: [00:01:22] The M-pox outbreak in the DRC is concerning for a couple of reasons. First, the number of cases is a lot higher than we've ever seen before. And although clade one M-pox is endemic in DRC, that country usually only sees a couple thousand cases per year. And last year they saw over 14,000 cases, suspect cases, and already in 2024, there have been nearly 4000 cases. So I do think that the number we're seeing is unusual and a cause for concern. I'm going to actually turn it over to Agam to talk a little bit more about clinically why we're concerned about this outbreak.

Agam Rao: [00:01:59] Thank you, Jenny. So severity wise, we may see more severe cases among patients with clade one M-pox than we've seen with the global outbreak that has been associated with clade two M-pox. Although there are some similarities between clade one and clade two, there are some differences as well. And some of those differences that make it concerning. First off though, if I could say some of the things that are similar about clade one and clade two, the lesions for clade one M-pox are similar in appearance. They have similar characteristics. They're firm, deep seated, sometimes umbilicated lesions. The infections can be transmitted similarly. Hospital waste is still similarly category B and the IPC recommendations gowns, gloves, eye protection and N95 standard precautions, those are all similar. Patient management is dependent on the severity of illness or potential for severe illness, and the therapeutics and the vaccines are similarly effective. But because we could see more severe infections, it is something that we are concerned about and want to ensure that clinicians are aware about. There could be infections that are more easily spread, and so adherence to the recommended CDC infection control precautions is also an essential part of ensuring that it is contained.

Jennifer McQuiston: [00:03:17] And I'll just jump in and say because of those severity differences, that's really the reason we issue that Health Alert Network advisory, or the HAN, as we call it. I think our goal was to raise awareness of the outbreak in the DRC and get clinicians really thinking about the possibility of that here if they see a traveler from DRC presenting with symptoms of of M-pox. And we wanted to encourage doctors to seek out a clade specific test. So that's what the HAM recommended. And the goal is just to diagnose it as early as possible so that patient can get isolated, it's contained and there's not onward spread.

Mati Hlatshwayo Davis: [00:03:54] Much appreciated, and you kind of went into the question I had next around similarities and differences. But can you expand a little bit more on what clinicians should be aware of as far as risk factors transmissibility? And you already talked about disease severity. So we can sort of focus on that risk factors and transmissibility.

Agam Rao: [00:04:14] As Jenny mentioned, there's some aspects of the outbreak that's currently occurring in the DRC that are concerning. Although clade one is known to be endemic in DRC and this is decades really that it's occurred there. This is the first time this is the first outbreak wherein we're aware of spread by sexual transmission. So unlike the clade two outbreak that we all are familiar with because it's been occurring globally since 2022, this is the first time that the clade one has been associated with sexual transmissions, and the sexual transmission has been reported in both men who have sex with men and heterosexual networks. So it's not limited to just sex among men who have sex with men. There's also heterosexual networks involved. And there's still also the more classic zoonotic spillover and household transmission scenarios that are causing cases there. So that is how transmissions might be different from what we're used to seeing with the clade two M-pox outbreak. And then in terms of other ways that it's different, severity as we mentioned, is one of the features. I'll turn it over to Doctor McQuiston to perhaps talk a little bit about laboratory testing and how that might be different.

Jennifer McQuiston: [00:05:25] The main way Mpox is diagnosed in the US right now is through a non variola PCR test. We call that the invio test. And that test is available at most state public health labs and most large commercial labs. It can pick up Mpox no matter what the clade is, but it can't differentiate them. It can't tell you this is a clade one patient or this is a clade two patient. There are other laboratories that can conduct a more detailed test that will identify clade one Mpox cases. CDC can do it, there are two public health labs in California that are currently conducting clade one PCR testing, and there are a lot more labs working on bringing that testing on board. There are also about 20 labs across the country that run both that invio test and a clade two PCR. For those labs, if you have an invio positive and a clade two negative, that would be a really strong signal that what they're looking at could be a clade one Mpox case. And so it would need closer investigation. There are also a bunch of labs that can sequence their specimens and that can also differentiate clades. So there is a capacity for clinicians to find a lab pretty easily that can provide insight into what clade that they're dealing with. And in particular, the large commercial lab right now that I know is conducting an invio test and a clade two test is Quest. They can certainly signal if there's something unusual indicating it could be clade one.

Mati Hlatshwayo Davis: [00:06:45] In terms of what you both talked about, with disease severity being really the concern here, would you advise clinicians to sort of go straight to the CDC route to try to get a clade one specific test, and should they make that decision based on severity, or does the CDC have enough capacity right now to kind of take all comers? What's your recommendation as far as how clinicians should make a decision about which lab to go to in these cases?

Agam Rao: [00:07:11] It's really important to understand that it's the severity of illness that really helps guide clinicians on how to manage a patient. While clade specific testing is helpful, it's really the severity of the illness that should guide clinicians in their decision making, regardless of what the clade is. Mpox infections occur across a continuum. So there are clade two infections that have been really severe, and there could be more that are clade one that are more severe. But the clinical decision making, when to start therapeutics, how to manage the patient and the inpatient setting, that's really going to be dependent on how severe the actual infection is. Clade specific testing could be helpful in ensuring that there's no spread beyond a patient, but the clinical decisions really should be made based on the severity of the illness in front of them.

Mati Hlatshwayo Davis: [00:07:57] And given what you just said about that, what are the current treatments available, and are there treatments that are specific to clade one?

Agam Rao: [00:08:04] Clade one and clade two viruses are more than 90% similar to each other. And so for that reason, we expect that the vaccine and all other therapeutics, Tecovirimat, Brincidofovir, Cidofovir, Trifluridine, ophthalmic solution, to be similarly effective for both clades. There have been animal models that have suggested that the vaccine provides strong protection against clade one, and the JYNNEOS vaccine is even FDA licensed to prevent Mpox regardless of the clade. We have good real world effectiveness data from this ongoing clade two Mpox outbreak that shows that the vaccine has worked to protect against clade two. We don't have that same real-world effectiveness for clade one, but there is a CDC study in DRC that shows it produces a good immune response and appears to protect health care workers in an area highly endemic for clade one. So clinicians should be reassured that the vaccine should be effective. They should encourage vaccination of people who are recommended to currently receive the vaccine, and know that the therapeutics can be used for Mpox, regardless of the clade.

Mati Hlatshwayo Davis: [00:09:05] And how easily available are those treatments? What's the process for clinicians to get them?

Agam Rao: [00:09:10] Well, these are out there therapeutics that have been stockpiled by the US government for prevention of smallpox. They can be acquired through consultation with public health authorities. So as a first step, we recommend clinicians reach out to their state and local health departments. Oftentimes, state and local health departments have access to these therapeutics already. If they don't, then they'll facilitate contact with CDC's 24/7 clinical consultation service, and we can do a consultation. We have provided over 250 of these consultations for severe manifestations of Mpox during the clade two outbreak, and will continue to do so. And we can provide advice about how to manage the patient based on our experience involved as consultants. For these over 250 cases, the JYNNEOS vaccine is is very commonly and easily available. And again, public health authorities can facilitate clinicians access to. That. I will just mention that even though we're talking about clade one during this conversation, the clade two outbreak is still going on. There are still clade two cases occurring in the United States. There's even deaths still occurring. As recently as October of 2023, the Advisory Committee on Immunization Practices, or ACIP, voted unanimously in favor of recommending the JYNNEOS vaccine for certain people at risk for m-pox during the ongoing outbreak. And this recommendation is now on the routine immunization schedule, and it's something that clinicians can talk to their patients about during routine clinic appointments, HIV clinic appointments, STD appointments, other routine appointments that they have with patients.

Mati Hlatshwayo Davis: [00:10:49] Yeah that was a very selfish question for me as a director of health for a large city, it was wonderful for you to immediately say, in consultation with local and state health departments, because I think people really underestimate how difficult, how more difficult it makes it for our case investigations, disease tracking, but also just for standardization of care. So I really appreciate you making that plug for me for free. While we're here talking a little bit about public health, let's talk about prevention. You've been really clear about the benefit of vaccinations, how easily accessible they are and how impactful they are. Would you say that there are other things that we should be pushing? And now I'm talking about us in the public health space by way of prevention methods?

Agam Rao: [00:11:29] Well, first of all, for just about the JYNNEOS vaccine, again pushing against again for clade two preparedness in addition to clade one. And just want to point out that only 1 in 4 people who are eligible to be vaccinated, 1 in 4 people who are recommended to be vaccinated, have received both doses of the JYNNEOS vaccine. And we do have this vaccine effectiveness data that very clearly shows that two doses is better than one dose and that cases are continuing to occur. So a plug for JYNNEOS vaccine for prevention.

Mati Hlatshwayo Davis: [00:11:59] But Agam, why do you think that is? Why? What do you think is the issue with folks getting it to begin with and coming back for round two? I'll share a little bit of my observations from the public health perspective, but from the CDC perspective, what do you think the barrier is there?

Agam Rao: [00:12:12] They're perhaps not hearing about m-pox in the media anymore. You know, case counts are much lower than they were at the peak of this outbreak. Substantially lower and out of sight, out of mind, sort of. So if we're not hearing about in the news, we assume it's not an issue. But in reality, cases really are occurring. There's never been a time when there were zero cases occurring on a seven-day average time period within the country. We want people to be vaccinated. We want to encourage clinicians to talk about it during their clinic appointments, so that patients will know that, that this is still a concerning issue in the United States, even though the case counts are lower.

Mati Hlatshwayo Davis: [00:12:48] Couldn't agree with you more. I think that out of sight, out of mind is huge. I think there's a little bit of what we saw with Covid, where people just want to have it out of sight. But I'll be honest with you, public health officials really struggled with messaging, and that's why the health advisory that you provided us with was enormously helpful, because we were able to really use language that came directly from the CDC that was de-stigmatizing, but that made clear that there are groups of folks that should really be prioritizing this. Right? And now that it's more easily accessible. I remember when M-pox first rolled out, it was like The Hunger Games, trying to get people vaccinated. We were in a Pep plus plus state in Missouri for six weeks. It was a nightmare. So now that we're on this side of it, it's just really difficult to kind of bring people to that understanding that while we're not trying to scare folks into some sort of like emergent state, that it's still important that they see it through. So I appreciate you talking about that. Are there other things that you'd like to see us prioritize in messaging around prevention, or do you want us to focus primarily on vaccination?

Jennifer McQuiston: [00:13:50] So I'm going to jump in here and say that we're on the cusp of actually commercialization of JYNNEOS, which will be another big boost, I think, in accessibility in coming months. So that's good. The difficulty is that we don't know exactly which groups might be at highest risk for clade one Mpox in the US. It sort of depends on kind of which networks it starts to circulate in that early epidemiology and work by the state health departments to kind of define what's driving transmission is going to be really critical to drive then our education messages out. And the data is now coming out showing that while vaccination is highly effective, what really worked to bring the outbreak under control globally last year was behavioral change in the population.

Mati Hlatshwayo Davis: [00:14:34] There we go. Yeah.

Jennifer McQuiston: [00:14:35] And I think we could be starting to see as Mpox dies down, behaviors starting to shift back that might promote risk. Whichever populations end up being at risk, if clade one came to circulate here in the US, it would be education and then those groups changing behaviors for prevention.

Mati Hlatshwayo Davis: [00:14:51] And when you say behaviors, can you be specific. What kind of behavior should we be talking about here?

Jennifer McQuiston: [00:14:55] Well, with clade two I think some of it was very large sexual networks, frequent parties. And so people were making choices to to limit sexual partners, I think. And that really helped bring the outbreak to a much more rapid conclusion than it might have otherwise. Depending on what's happening, if this is primarily spreading in households, I think we would be really recommending, for example, isolation of a patient. And if you can't do it safely in a household, find another place to isolate them until they're no longer contagious. So it really depends on what I think the transmission drivers are.

Mati Hlatshwayo Davis: [00:15:28] And for folks who don't know, can you talk a little bit about how long isolation is?

Jennifer McQuiston: [00:15:32] It may vary by patient. It's usually a couple weeks at least, and it's because a patient is infectious until their scabs heal over and then separate off.

Mati Hlatshwayo Davis: [00:15:41] Right.

Jennifer McQuiston: [00:15:41] And so if somebody only has one lesion and they're able to keep it really covered, they might even be able to come out and have contact sooner than someone who has widespread lesions. So it really varies a bit based on patient presentation and time to healing.

Mati Hlatshwayo Davis: [00:15:53] And that was another challenge. I think with the low number of patients we see, health departments are very equipped to help with access issues and areas where there's disparities, because really needing to isolate in place for weeks at a time is a major challenge for minoritized and vulnerable populations. But given the sheer numbers, I just think that this is where clinicians need to be in close contact with public health departments and all of the networks that we have around available housing and our social networks, because it's critical and it's not as easy as, for example, a five day to seven-day isolation period for Covid.

Mati Hlatshwayo Davis: [00:16:28] I've loved the way that we've been able to lay out the conversation around prevention. We've had a really robust discussion around diagnosis as well and treatment. So what should clinicians know to help from an individual patient care and public health standpoint, outside of what we've really spoken about? I'm challenging us to think about we have someone in the room with us. Are there other things that we should be paying attention to as we deal with the individual patient?

Agam Rao: [00:16:54] Well, at this time, nearly all specimens confirmed to be an orthopoxvirus infection in the United States are being evaluated by clade specific testing, and there have been no clade one cases identified in the United States. In fact, there have been no clade one cases identified outside of any African country where it is endemic. But if a clinician sees a suspected case of Mpox in a traveler from the DRC, just because we know that there is that outbreak occurring there, we would want to expedite clade specific testing, and they can do that by contacting public health authorities so that clade specific testing can be expedited. And perhaps even though the clinical management of the patient won't change depending on the clade results, you know, the severity of the illness is still going to dictate how a patient is cared for, what sort of interventions, what sort of therapeutics are provided. It's still knowing the clade as soon as possible could still help with isolating, contact tracing, identifying the source of it, just preventing spread within the community in general, and keeping any clade one outbreak as limited as possible.

Mati Hlatshwayo Davis: [00:18:00] Thanks so much. Dr. McQuiston, anything to add to that?

Jennifer McQuiston: [00:18:01] The thing I would add is that we really buried the lead here and Agam just brought it out. We don't have any clade one cases, no evidence of clade one cases in the United States right now. So, you know, just because a clinician sees a patient with a severe presentation doesn't mean that it's clade one. But if they do see something that they feel is unusual, this isn't a traveler, for example, or they're seeing an unusual number of household members reporting similar symptoms. Definitely alert the state and local health authorities, and they can work with CDC or other local labs to expedite testing and really get answers and lock it down. I think that the thing we want to do with the first imported clade one cases, should they happen, is lock them down so that we don't get onward spread. We want to keep them as little as possible.

Mati Hlatshwayo Davis: [00:18:46] Well, that's the motto, folks. Lock them down, from Dr. McQuiston at the CDC, I love it. So before we close out, I would just really love us to talk about and for you to take us through what is the CDC doing to prepare for potential clade one outbreaks here in the US right now?

Jennifer McQuiston: [00:19:03] So CDC is working hand in hand with our other US government partners. I mean, we work really, really closely with ASPR for preparedness and for vaccine therapeutics. We work with NIH and FDA as well, and we work really closely with our state and local health department. So we're kind of all working hand in hand to make sure we're as prepared as possible. So right now the risk in the US is considered low. They've only got cases really in the DRC and maybe some other endemic countries, and very few travelers come here. But if cases start to be reported in other countries, especially if it started to circulate in Europe, those risks in the US are going to increase. And so we're monitoring what's happening and those surrounding countries and also in Europe, as closely as we can, to give us as much advance notice of a potential increased risk. Here we are expanding the availability of clade one PCR tests so that more labs have them. And there's, you know, maybe less hunting that a clinician or a state health department has to do to find somebody who can expedite the test. Then we're really fast tracking that. So we think in the next couple months a lot more labs will have clade specific testing on board. And then maybe most importantly, people may not realize this, but we're working in DRC because the best way to stop the outbreak from being a risk here is to help stop it there before it really spills over and becomes a global concern. So we do have staff on the ground helping DRC think about approaches. The US government is working, along with other governments around the world, to try to find vaccine that could go into DRC to help them begin to vaccinate and control spread. So there are a lot of things that are happening on that side as well.

Agam Rao: [00:20:45] If we were to see any clade one Mpox cases in the US, we would probably, at least for the first several cases, admit those patients for management and isolation so that we can have a really good understanding, as good an understanding as possible, about how clade one is presenting and impacting patients in the United States and develop guidance accordingly. So right now we have interim treatment clinical guidance considerations that have been published, that were published in March of 2023 by CDC, that talks a lot about the approach to severe manifestations of Mpox. We believe that the approach would be similar, but if clade one cases were identified in the US, we would just want to ensure that regardless of the severity of the illness, that we had eyes on those cases and could update that guidance accordingly.

Mati Hlatshwayo Davis: [00:21:28] Well, this has been an incredible podcast. I especially am biased because I don't think we do enough of getting our CDC leadership with us in a timely fashion at the beginning of outbreaks like this, when clinicians have most of their questions and we're, quite frankly, clinicians who don't see these types of infections are unaware. As a public health provider, it's also wonderful to really hear directly from all of you about how you're seeing this, as it helps us to better prepare the public and to really hone in on preventative messaging. So I'm very, very grateful. Thank you so much for joining us, Dr. Rao, Dr. McQuiston, this has been Dr. Mati Hlatshwayo Davis, director of health for the City of St. Louis, for Let's Talk ID. This episode was produced by the Infectious Diseases Society of America and edited and mixed by Bentley Brown.