Poxviruses, outbreaks, and Ebola: A Q&A with a retiring CDC expert on bad bugs

In the last week of August, one of the world’s foremost poxvirus experts retired from the Centers for Disease Control and Prevention.

To outside eyes, the timing of Inger Damon’s departure could be seen as odd or unfortunate, given that after years of relative obscurity, poxviruses are at the center of the world’s infectious diseases radar, thanks to the ongoing monkeypox outbreak. Though the growth of case numbers had slowed, there was no sign the crisis was under control. Many challenges remain ahead.

But Damon and her husband, also a CDC scientist, had announced their intentions to retire before the monkeypox outbreak was detected in the spring. The global spread of the virus — which Damon believes can be contained, but not anytime soon — didn’t alter their plans.

Damon headed the CDC’s Division of High-Consequence Pathogens and Pathology — think the baddest of bad bugs. Ebola and rabies, anthrax and smallpox, Rift Valley fever and monkeypox. She took the job in the spring of 2014, when Ebola was exploding in an unprecedented way across West Africa. In the intervening years, her group has rolled from crisis to crisis.

Retirement for some means adventure travel or long daily walks, reading for pleasure, or the exploration of new hobbies. In Damon’s case, there’s lots of work left on the horizon. She is a member of the World Health Organization’s committee tasked with investigating the origin of the Covid-19 pandemic, sits on the global health agency’s advisory committee on variola virus research, and is a member of the poxvirus study group of the International Committee on Taxonomy of Viruses.

She’s even offered to help out colleagues in her old group, if they need her.

“I said I would pitch in on a volunteer basis to help as needed, if I could pitch in,” Damon told STAT in an interview during her last week at the CDC. “We’ll see if they take me up on it.”

In the interview, she discussed the years of work that gave the world tools with which to respond to the monkeypox outbreak — a safer vaccine, an antiviral drug, diagnostic tests that were available from the jump.

This transcript of the conversation was edited for length and clarity.

It’s an unusual time for one of the world’s leading poxvirologists to be leaving a job like this.

I guess I’d say I’m at a point where I look back and I say: I’ve been able to contribute to this. I’ve been able to work with folks here at CDC and helped develop the diagnostics that are being used now, whether in public health labs or in the commercial labs. I’ve helped to train a generation of virologists and clinicians who are comfortable thinking through this disease and the complexities of it. I worked to help train and think through what we need to do to understand disease ecology. I’ve helped other people in countries where disease is thought to be endemic in terms of working with the Democratic Republic of Congo, or outbreaks in the Republic of Congo, or helping train the people who are supporting work in Nigeria now, whether it’s sequencing or diagnostics or doing fine-tuned epidemiologic studies to understand risks. So I feel like I’ve contributed to what we’re doing now, and I feel like we have a really great, trained cadre of people ready to go out and further spread knowledge.

There’s lots of smart people coming up. So they’ve got it covered.

Your division at CDC, high-consequence pathogens, covers a lot of bad actors.

It certainly does.

Over the course of your career, is there a pathogen that has given you more sleepless nights than others?

That’s a hard question! I’ve had lots of sleepless nights. I’ve had sleepless nights about working in the BSL-4 lab with variola virus [the eradicated virus that caused smallpox], and doing experiments there to grow virus for sequencing, or for doing studies looking at antiviral efficacy in non-human primates.

I’ve had sleepless nights thinking through Ebola response activities, and the Ebola response in the U.S. in 2014 to 2016. And internationally, it was just a tremendous lift of: How do we get done what initially seems impossible and make it possible?

Do you have a favorite pathogen?

[Laughs.] I would say a favorite pathogen would be to unlock the mysteries of what allowed variola virus to be such an efficient human pathogen. I don’t think that’s something we’ll ever understand. It’s a mystery that we will probably never solve.

Let’s go back to monkeypox. It really found a lane, didn’t it? A way to get out into the broader world by infiltrating networks of men who have sex with men.

Yes, and I think it was also at a time when people had been confined at home for a couple of years because of Covid, hadn’t had the usual freedoms or experiences. And so it seemed to be a time when Covid vaccine was there and we could take our masks off. It was a time when people could interact with each other in a more social way.

I was emailing recently with Anne Rimoin, [a monkeypox expert at the University of California, Los Angeles]. She has serious concerns about how well the monkeypox vaccine will work in the current context, where a lot of people being infected are contracting the virus across mucosal membranes. Her argument was these vaccines weren’t created to protect against this kind of intense exposure. Do you worry about that?

I do. I think this is something that we have to very carefully follow. And we need to really be very forthright in helping the community who is at risk understand what the limitation of our knowledge is, and why and what we do know about different manifestations of the virus through different routes of infections. That’s certainly something we learned more about in 2003 in the U.S. outbreak. There were different ways that illness rolled out, whether you’re infected through a bite or a scratch.

Here we’re seeing very severe pharyngitis [sore throat]. We’re seeing severe proctitis [inflammation of the lining of the rectum]. We’re seeing really severe lesions on the glans of the penis, which are incredibly painful, and in uncircumcised men are really creating challenges in many cases. And so I think, getting the message out about what we know, about what we’re seeing at this point in time is critical for people to make informed decisions.

Monkeypox activity in Nigeria from 2017 onward seemed to suggest something different was happening there. Did your group think the virus had gotten into men who have sex with men there?

If you look at the Lancet ID paper and the CID paper that came out from Nigerian co-authors [in 2019 and 2020] this is where you’re starting to see more evidence and descriptions of penile lesions. And we’re seeing death in those with HIV which is unmanaged. This had not been reported before. The male-to-female ratio is slightly higher than what was reported in other studies, where the belief is that the primary exposure was hunting or food preparation.

There was nothing that was like a smoking gun. But there were clues that there was disease in a different demographic.

Do you have a sense of whether this spread internationally is going to be contained? Do you think it’s possible?

If we look at the trends in case counts, we’re beginning to see a leveling off, and in some cases a decrease in case counts. And so that’s a good sign.

So I think what we need to know is what has led to that? What were the effective interventions? And then we need to multiply those. And we need to make sure we’re reaching all of the communities in a way that they understand the impact of those interventions and the benefit of those interventions. And I think we’re beginning to be at that place in the U.S. outbreak.

That doesn’t really answer my question. Do you think it is going to be contained, or can be contained?

[Long pause.]

I do. But I think it’s going to take some time. And I’m not going on the record about how much time it’s going to take.

People keep talking about it in the context of stopping the outbreak in their own country. If monkeypox is stopped in the United States but takes root in Romania or Israel or Portugal or some other country, it’s winning a battle but not the war.

Yes. It really has to be a global effort, otherwise it will simply be reintroduced again.

Is this teaching us that we may need to help endemic countries add monkeypox vaccine into their vaccination schedules?

The decision not to continue with routine smallpox vaccination [after smallpox eradication] was based on studies in the Democratic Republic of the Congo in the 1980s. What the studies eventually showed is that they felt that absent reintroduction from a reservoir host that monkeypox would not perpetuate in humans. There was a recommendation that routine smallpox vaccination [which also protects against monkeypox] was probably not going to be of benefit.

I think we’re at the crux of the corner of what do we now think about the role of vaccination here? As this outbreak evolves, will we need to go back and see if there are additional populations that we think are at continued risk? Or have we done an adequate job to control this and eliminate further disease spread?

So it could be that vaccine will become a tool that will be used in populations that are considered to be at risk — that the risk-benefit ratio is worth it. But we’re not quite there yet.

If I’m hearing you correctly, you’re at least open to the notion that the calculations that were done based on the studies in DRC decades ago don’t address the current context?

Correct. They’ve changed.

It’s only been a few months since the U.K. announced it had found monkeypox cases among men who hadn’t traveled outside the country but who had sex with other men. Has anyone done any research yet to show whether the mutations seen in the viruses in this outbreak have given monkeypox a better shot at human-to-human transmission?

I have not seen anything published yet, or anything in preprint yet about that. I do know that there are a number of investigators who are looking at that. I’ve heard early descriptions but I’ve seen no data.

The challenge is developing an animal model that is going to give you the information that recapitulates what we’re seeing in the human population.

How do you do that with this transmission scenario, where people are largely being infected during oral and anal sex?

Yup.

Do we do mucosal challenges? What is the right host whose immune system — innate, adaptive — is representative or can be studied to inform the human system? What we’ve been pushing on for a long time is that there really needs to be some good, well-done natural history studies of humans, where individuals who come in for care are followed closely. The evolution of rash is evaluated. A good history is taken about potential routes of infection. Contacts of that individual are enrolled. They’re monitored or assessed. You get information about potential risks. That may be the richest source of information to help us understand the baseline of what’s happening in this particular outbreak.

When you think about this outbreak — which is kind of a fascinating way to cap a career at CDC — are there things that you learned about monkeypox that really floored you?

I guess what I would say is, there are things that I’ve seen in this outbreak that make me ask more questions. More questions than I had before. There’s all sorts of really fascinating questions about the virus and the host and the virus-host interaction.

And then I think there are the preparedness and response questions. How do our vaccines work at this point in time? What can we tell people about their effectiveness and how they’re going to protect? What do we need to learn about the antiviral that’s being used? When is it best used? How does it affect disease? How does it affect illness?

What does retiring from the CDC mean? You’ve offered to help out if you can. And you’re going to continue to work on WHO committees, aren’t you? Will you end up at a university?

I’m going to take a couple months off and travel and go to a bunch of weddings and catch up on the talks that I haven’t written yet and the book chapter that’s overdue.

In other words, you’re not going to be in a hammock sipping piña coladas?

Some of the time. Just maybe with my laptop.

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