Lessons From the Mpox Response


During the summer of 2022, mpox (then known as monkeypox) was spreading rapidly across the US, largely affecting gay and bisexual men who have sex with men (GBMSM).1 Fifteen months later, the outbreak looks very different. Cases are down to an average of approximately 1 to 2 per day (from a peak of 600 per day),2 the summer 2023 wave that was widely predicted did not materialize, and the clusters that occur now are quickly controlled (Figure). How did we get here? And what did the lessons of the mpox response teach us about managing future outbreaks? Even though the biomedical tools (tests, vaccines, and therapeutics) were available at the start of the outbreak, how they were deployed provides important lessons. There are 3 key lessons from the response that can help better manage infectious disease outbreaks in the future.

Mpox Epidemic by Week for 2022-2023

Based on data from the US Centers for Disease Control and Prevention.

The primary strategy for mpox containment was to take an approach that deeply engaged the community most affected. Rather than the community as the object of a public health intervention, they became the vehicle. The views (often criticisms) of those most affected by the virus were used to inform policy and create shared accountability. One example was creating the equity mpox workshop composed of GBMSM and transgender racial and ethnic minority individuals. This monthly workshop, suggested by a prominent member of the GBMSM community, provided feedback to the White House that helped calibrate the community-driven response. The White House Mpox Response Team (WHMRT) built trust among the community by engaging, listening, and acting on their suggestions. In return, the community became the trusted messengers.

A variety of strategies were used to distribute information from accessible webinars to infographics circulated on social media. These communications allowed local and state public health leaders to transparently answer questions on the minds of community members. One key lesson from the COVID-19 response was that outbreaks create information needs and filling those needs with high-quality, easily comprehensible information is critical to prevent misinformation from propagating. Letting the community identify the information needs and then transparently filling those needs, including acknowledging scientific uncertainty, was critical to managing the mpox outbreak.

A second lesson from the mpox response was that public health responses must be flexible and responsive. Even though vaccines were available in traditional places for administration (such as physician offices and retail pharmacies), the community partners emphasized the importance of also making vaccinations available where those who would most benefit were likely to be present and comfortable. Applying lessons learned in HIV-related outreach, vaccines were offered in safe spaces outside night clubs, pop-up events, social venues, sex parties, and other community-focused events such as Atlanta Black Pride and Southern Decadence.35 This level of community engagement enhanced equity in mpox vaccination and better aligned vaccine providers with the community they served, both of which were essential to curbing the outbreak.

Risk assessment is another example of a key change made due to feedback from community partners. After initially using the traditional public health approach of conducting risk assessments before administering vaccines, we quickly heard from community partners that risk assessments are often stigmatizing and could dissuade many of the highest-risk individuals from even engaging. Therefore, the need for extensive risk assessment was removed and trusted partners were leveraged to help identify the people most likely to benefit from vaccines, education, and prevention messaging. We also heard clear concerns that the temporary mark left at the mpox injection site might disclose information on sexuality or gender identity. More flexible clinical guidance was adopted that allowed the vaccine to be administered on less visible parts of the body, and encouraged people to express a preference for the injection site. This seemingly small change may have had a large effect on both creating greater vaccine acceptance and generally building community trust.

The third lesson was the importance of flexible resources and investments in public health infrastructure for preparedness and rapid response during public health emergencies. When the Secretary of the US Department of Health and Human Services determined that mpox had the potential to become an infectious disease emergency, public health officials were able to use the US Centers for Disease Control and Prevention infectious diseases rapid response reserve fund to deploy resources quickly. Public health officials working on HIV and sexually transmitted infections prevention activities were able to conduct mpox prevention work in conjunction with these ongoing activities. Given that the communities most vulnerable to mpox overlap significantly with those most affected by HIV (between 35%-47% of those diagnosed with mpox also had HIV),6 drawing on the capabilities and infrastructure that already existed for HIV proved extremely useful in containing the mpox outbreak. The WHMRT also coordinated activities across the US Department of Health and Human Services and the US Department of Housing and Urban Development to provide additional resources for the response.

Beyond those 3 key elements of the response, there is one more critical issue to consider. As the number of new cases declined during the fall of 2022, there was intense pressure to bring the mpox response to an end and fold it into ongoing public health work around sexually transmitted infections. It is tempting to see declining case numbers as an invitation to declare the effort a success.

Despite what is often a short attention span of policymakers, the White House recognized that declining case numbers or even an end to the declared public health emergency should not end the mpox response. The WHMRT was concerned with the disproportionate effect mpox had on Black and Latino communities and people living with HIV and recognized that mpox required ongoing attention and critical work to prevent resurgence.7 Instead of pulling back, the WHMRT redoubled its efforts in the spring of 2023 to build trust and vaccinate those who were vulnerable. As we neared the summer and seasonal festivities that could increase opportunities for the virus to spread, the team made additional efforts to partner with event organizers and the communities they serve to provide people with a holistic toolkit to inform their decisions about how to keep their summer healthy.8,9 The lack of a second wave of mpox this past summer was due in large part to the ongoing work with the communities most affected and the decision to continue driving awareness. Persistence is the key lesson. Even after the infection numbers decline, it is paramount to prevent outbreak resurgence.

The last few years have been remarkable in how infectious diseases have taken a toll. The lesson from the mpox response is clear: community engagement and flexibility of response are necessary as well as the existing public health infrastructure that can be deployed to manage outbreaks. Medical countermeasures are key, but so are community partnerships, flexibility, and persistence. That is how infectious disease outbreaks should be managed now and in the future.

Early Tecovirimat Treatment for Mpox Disease Among People With HIV


Key Points

Question  Is use of tecovirimat within 7 days of mpox symptom onset associated with lower rates of mpox disease progression among people with HIV (PWH)?

Findings  In this cohort study including 112 PWH after propensity matching, those treated with tecovirimat within 7 days of mpox symptom onset compared with those who were treated after 7 days or who did not receive tecovirimat were 13 times less likely to progress to severe mpox disease.

Meaning  The findings of this study support the use of tecovirimat in all PWH as soon as mpox is suspected.

Abstract

Importance  Despite a lack of effectiveness data in humans, tecovirimat was widely prescribed to people with HIV (PWH) with mpox during the 2022 mpox epidemic, particularly PWH with low CD4+ T-cell counts or severe mpox clinical manifestations.

Objective  To evaluate if PWH with mpox who were treated with tecovirimat within 7 days of symptom onset were less likely to have mpox disease progression.

Design, Setting, and Participants  This cohort study included PWH diagnosed with mpox at 4 hospitals in Atlanta, Georgia, between June 1 and October 7, 2022. Patients were grouped according to whether they were treated with tecovirimat within 7 days of mpox symptom onset (early tecovirimat cohort) or they did not receive tecovirimat or received the drug 7 or more days after symptom onset (late or no tecovirimat cohort). Multivariable logistic regression models were used to identify factors associated with progression of mpox disease. The 2 cohorts were then matched 1:1 using propensity scores based on the identified factors, and mpox disease progression was compared.

Exposures  Treatment with tecovirimat within 7 days of mpox symptom onset.

Main Outcome and Measures  Progression of mpox disease, defined as the development of at least 1 severe mpox criterion established by the US Centers for Disease Control and Prevention, after symptom day 7.

Results  After propensity score matching, a total of 112 PWH were included in the analysis; 56 received tecovirimat within 7 days of mpox symptom onset (early tecovirimat group) and 56 were either treated later or did not receive tecovirimat (late or no tecovirimat group). In the early tecovirimat group, the median (IQR) age was 35 (30-42) years; 54 individuals (96.4%) were cisgender men, 46 (82.1%) were Black individuals, and 10 (17.9%) were individuals of other races (American Indian or Alaska Native, Asian, Native Hawaiian or Other Pacific Islander, or White) or unknown race. In the late or no tecovirimat group, the median (IQR) age was 36 (32-43) years; 54 (96.4%) were cisgender men, 49 (87.5%) were Black individuals, and 7 (12.5%) were individuals of other races or unknown race. Mpox disease progression occurred in 3 PWH (5.4%) in the early tecovirimat group and in 15 PWH (26.8%) in the late or no tecovirimat group (paired odds ratio, 13.00 [95% CI, 1.71-99.40]; P = .002).

Conclusion and Relevance  Results of this cohort study support starting tecovirimat in all PWH as soon as an mpox diagnosis is suspected. Additional research is warranted to confirm these findings.

Introduction

The 2022 global mpox outbreak disproportionately affected people with HIV (PWH).1,2 This population may develop more severe mpox disease manifestations and worse clinical outcomes,3,4 especially individuals with lower CD4+ T-cell counts5 and nonsuppressed HIV viremia,6 highlighting the urgent need for effective therapeutic agents for this population.

Tecovirimat (ST-246), an antiviral agent developed to treat smallpox, has antiviral activity against other orthopoxviruses, including mpox virus. In animal models, tecovirimat was shown to prevent morbidity and mortality associated with mpox, especially when started within 5 days of mpox inoculation.79

Based on these data, the US Food and Drug Administration approved tecovirimat for mpox treatment using expanded access for an investigational new drug. Data showing the effectiveness of tecovirimat for treating mpox disease in humans are lacking.10,11 Meeting enrollment goals for a randomized controlled trial assessing the efficacy of tecovirimat for mpox infection (the STOMP [Study of Tecovirimat for Human Monkeypox Virus] trial12) has been challenging due to declining number of mpox cases. We aimed to perform a matched cohort analysis to examine the association between early tecovirimat treatment (started within 7 days of mpox symptom onset) and progression of mpox disease among PWH.

Discussion

In this prospective matched cohort analysis, PWH with mpox disease who were prescribed tecovirimat within 7 days of symptom onset were significantly less likely to have progression of mpox disease compared with PWH who were not prescribed tecovirimat within 7 days of symptom onset. Results of the present study suggest that tecovirimat treatment should be started early at the time of suspected mpox diagnosis in all PWH, especially in those with nonsuppressed HIV viremia or mucosal site involvement.

Limitations

This study has limitations. First, it is possible that unmatched confounding variables could have contributed to fewer cases of severe mpox disease being observed in the early tecovirimat cohort. Second, this study has a small sample size and is inadequately powered to examine specific mpox complications or mortality. Third, most of our population (84.8%) were Black individuals, which reflected the population affected by the 2022 mpox outbreak in Atlanta but may limit generalizability to populations with different races and ethnicities. Fourth, the timing of tecovirimat initiation was determined based only on the time that the tecovirimat prescription was written, and we could not confirm if individuals took the medication or for how long. Fifth, we did not evaluate adverse events associated with tecovirimat. A large cohort study previously reported that tecovirimat is well tolerated.11

Conclusions

To our knowledge, this cohort study represents the first controlled analysis of tecovirimat for the treatment of mpox disease in PWH. The findings support starting tecovirimat in all PWH as soon as an mpox diagnosis is suspected. Additional research is needed to confirm these findings.

Where Did All the Monkeypox Go?


Mpox questions answered by Demetre “Doctor D” Daskalakis

Photo of Dr. D over a background of the monkey pox virus.

Within months of first hearing about monkeypox spreading outside of endemic areas, Demetre Daskalakis, MD, MPH, was appointed deputy coordinator of the White House Monkeypox Response Team.

MedPage Today sat down with Daskalakis to discuss the transformation the epidemic has been through, from a rocky start with fear and few answers to now just a trickle of cases of what was recently renamed “mpox” in order to reduce stigma and racism.

Testing, vaccination (Jynneos), treatment (tecovirimat, Tpoxx), community cooperation, and a mass targeted communications campaign that was particularly aimed towards LGBTQ+ communities slowed the virus such that the mpox epidemiology (epi) curve has returned to where it was in June. The Biden administration announced last week that mpox will no longer have health emergency status after January.

That progress was not without many bumps in the road.

Stigma, conspiracy theories, and politics were great enemies of the virus from day one. Mpox Clade IIb is most transmissible during human skin-to-skin contact and thus highly transmissible during sex. The community of men who have sex with men (MSM) accounted for more than 95% of cases; and particularly severe cases were found in people co-infected with HIV.

Daskalakis had both pandemic experience as former senior lead on equity in COVID-19 data and engagement for the New York City Department of Health and Mental Hygiene and an “in” with the LGBTQ+ community from his work in HIV prevention and his transparency about being a gay man.

Daskalakis is a self-described “queer health warrior.” As the founder of the Men’s Sexual Health Project, he went to sex clubs and bathhouses to test men for HIV and other sexually transmitted diseases (STDs) to help direct them to treatment. For mpox, that meant getting vaccine to gay events, testing and treating in STD clinics, and meeting people “where they were.” He also tackled equity challenges, particularly in reaching Black and Hispanic communities, and challenges educating health professionals about potential stigma.

Not shying away from a fight with stigma, Daskalakis playfully took part in a campaign endorsing NYC’s promotion of open conversation about sex and drugs between patients and their doctors, posing shirtless for the “Bare it all” campaign, baring his muscles, tattoos, and a big smile.

His bold strokes as a doctor and as a communicator have been both applauded and criticized.

“Don’t be jealous because he also looks better than you with his shirt off,” David Holland, MD, an infectious disease specialist at Emory University in Atlanta, tweeted in response to negative comments about images of Daskalakis clad in a leather harness. “He’s a brilliant scientist, tireless public servant, and has always worked right on the front lines, including this amazing ad campaign.”

The conversation with Daskalakis that follows has been lightly edited, mainly for length. It occurred before the virus was renamed mpox.

What did you carry forward from the HIV and COVID-19 outbreaks into the monkeypox outbreak?

Daskalakis: From the monkeypox perspective, I think that the lessons we learned from the COVID-19 pandemic are that complications are expected; they’re not surprising. You learn that in HIV, and you learn that in COVID. So really, it’s critical to take a proactive intentional path when doing public engagement and addressing the issues right from the start.

With that said, it still didn’t work perfectly for monkeypox.

We still have inequities, and we still have challenges. Some of that is just based on logistics. When you don’t have enough vaccine at the beginning of the outbreak, it’s really a challenge. But I feel like the strategy of trying to increase vaccine [supply] is one of those important equity interventions, along with moving to do testing quicker — that’s a lesson from COVID-19.

I definitely think the messaging is less about the details of what you say and more about the fact that you [as the government-appointed person leading this] need to have humility in terms of what you know and what you don’t know. And so, I feel like that is my mantra from COVID-19 actually, and also for monkeypox: Risk messaging is of critical importance; and being able to sort of say “I know this” and “I don’t know this” and “what I know today is going to be different tomorrow,” that changes everything.

The data show that people are still getting infected after they get the vaccine. Does that reflect the vaccine or behavior?

Daskalakis: None of that is surprising. No vaccine is 100%. We are going to learn more about the vaccine efficacy as we go forward, but I think definitely that post-vaccination infections are to be expected.

It’s not good harm-reduction to expect or to tell people to change their behaviors for life for a virus that is like this.

I always go back to thinking about early HIV and having the desire for people to change their behavior for HIV. It worked for a while. But you would have to get people to change their behaviors for a couple of generations to get rid of HIV. This one [monkeypox], you don’t have to change behaviors for generations; it’s for a few months. Once you build your force field of immunity with vaccines, people can make their own informed decisions about their risk. If I’m still willing to accept any risk, I may cool some of the things I would normally do, but if I’m willing to accept more risk I may not. But I will have some confidence that I have some level of protection. That’s harm reduction. That’s the way to do this.

The second dose of vaccine brings you to a higher level of protection based on lab data. I’m not a vaccine efficacy expert, but we tend to see the epi curve going down. It shows you whatever we have done so far with behavior, and people who have had infections are immune, all those things come together to really get us to a place where we’re controlling this outbreak.

Will we see this virus eradicated?

Daskalakis: I think a long tail is what we can expect. This outbreak went straight up, and it’s going down. Do I think we’re going to get to zero next week? No. Will we have weeks when we get to zero? I think yeah. Not quite yet.

This is where we have to ante up and move faster with the vaccine, because it’s working. We’ve seen some softening in vaccine demand, and so we just need to sort of get the word out and keep magnifying it. This is not the time to back off. The more protection we can get during this peaceful lull, the better we are in long-term infections.

What are the long-term effects of monkeypox infection?

Daskalakis: Definitely there is some concern about long-term scarring, like skin scarring. There’s the potential for scarring in places you don’t want to scar, that can cause urethral and rectum stricture.

But we know this virus is not going to recur. Once it’s gone, it’s gone. We have to watch carefully — there are so many post-viral syndromes people have. It’s super important for us to see longitudinally what happens to folks.

What has been your biggest challenge working in the White House?

Daskalakis: When Bob [Robert Fenton, White House national monkeypox response coordinator] and I started the job, President Biden said, “I really want you to make sure we’re improving the health of men that have sex with men, and especially those of color.”

I was like, “Yes, sir!” I can’t believe I signed up for this. It wasn’t in my bingo cards to be in the White House, so if this is what the boss says, well this is great. This is what I want to do. Let’s do it!

So the biggest challenge has been the normal outbreak stuff — trying to be as transparent as I can with what we know and what we don’t know. Sometimes it’s fraught with complications. What do we know enough about to say? And what don’t we know enough about to say?

In terms of signing up to get what the community needs, I can say with confidence that the Biden administration strategy worked, as demonstrated by our epi curve. But I feel like the fact that the foundation of the response was engagement with the community just tells you that that’s where it all starts.

Do you know of any other country that has approached the epidemic the way the U.S. did, by reaching out to vaccinate the MSM community at gay pride events?

Daskalakis: One of the biggest successes is San Francisco, where they made the magic happen [getting the number of cases down to zero quickly]. The bottom line is getting vaccines out. One of the most important events in my opinion was Black Pride in Atlanta, where we gave 5,000 vaccines and 4,200 injections were administered.

We really try to take strategies to improve equity programmatically but also by addressing some of the important barriers that are experienced, like people saying “I don’t want this mark on my forearm” [out of concern for stigma]. So we worked with the FDA and the CDC and we were able to move to other sites that people can receive vaccine, like the upper back.

I feel like we are kind of unicorns in this. It shows that this is the way to do it.

Did it take too long to decide monkeypox was “like” an STD?

Daskalakis: I feel like we can say with great certainty that monkeypox has been transmitted with close physical contact associated with sex.

From the programmatic perspective, we’re treating it with a syndemic strategy, and the way we’re doing it using sexually-transmitted infection and HIV resources signals so much about the right way to control the outbreak.

It’s really more the “how” than the semantics of it. Every state is able to decide if they want to move it into an STD category. So, for example, New York did that; for some 90-day period, they are calling this an STD, so that there is access to resources already there.

Our signal is to use the HIV infrastructure to address this, and people responded really well to that.

Is there ongoing funding for monkeypox?

Daskalakis: There’s no specific funding that’s been allocated for monkeypox. We sent a supplemental request that wasn’t funded. We need a longitudinal plan.

You’ve advocated home testing. How would home testing affect the ongoing surveillance and statistics on monkeypox?

Daskalakis: I come from that HIV space, where sometimes you have to give up something to be able to make movement in other things. People that are going to order home tests are going to be motivated to action in other ways. And so thinking about HIV home testing, which was the grandparent of COVID-19 home testing, this really shows us how you reach people you’re not going to reach when you have lab-based, provider-only testing.

When you look at the HIV home testing data from the CDC, 26% of the people that ordered a home test had never been tested before. That is way higher than what you would expect.

It’s a “power to the person on the street” issue for me. That’s so important, that if you’re not going to build a testing center where people will come, then if you can get the test to them — even if it causes a little bit of a pause in data or difficulty understanding the data — that home-based testing ends up becoming really important. I feel pretty strongly that you can’t hold the operational and programmatic things that you know can improve your outcomes hostage for perfect data.

The reality is that a multiplex test in the lab is really important for monkeypox, like a point-of-care test. As seen with secondary syphilis, for example, people tend to come to point of care because they’ve got something going on.

For people that may be symptomatic but don’t need to go get clinical care for monkeypox, who don’t want to go into an environment where “Oh! I have to disclose my sexuality, or this disease potentially discloses in some people’s minds my gender identity,” I think there’s high utility in that.