With attention to mpox fading, health officials fear infections will go undetected and unreported

In the transmission heyday of the international mpox outbreak early last summer, it appeared that containment might not be possible. In recent months, though, the rate of growth of new cases has slowed considerably in a number of countries. In the United States, daily case reports have been in the single digits since mid-December; the U.K. hasn’t reported a new case since before Christmas.

As the trajectory of the outbreak has shifted, mpox has faded from the public discourse. But the dwindling case counts obscure an important reality: The global footprint of a disease that until a few years ago could only be contracted in remote parts of a few countries in West or Central Africa has expanded substantially.

The risk still remains very low for most people, but one can now catch mpox (formerly known as monkeypox) in Europe, in North, Central or South America, or elsewhere. In fact, in Paraguay, Panama and El Salvador, case reports are rising. Last August, a family of four — father, mother, two young daughters — contracted the virus in Southern France, French researchers reported recently.

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The explosive period of the outbreak is now over, but the outbreak itself is not, said Rosamund Lewis, the World Health Organization’s point person on poxviruses.

“The future is going to look different from the past. The poxviruses are here with us to stay. We will learn a lot more about them, and they still reserve many surprises for us,” Lewis told STAT.

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Mpox has been reported in 110 countries since the outbreak hit the world’s radar last May, accounting for 84,000 cases and 74 deaths.

Regions where mpox hadn’t been seen before last year “will continue detecting either importations where [surveillance] capacity has been greatly enhanced, or local cases where they weren’t previously considered,” she said. The WHO expects “case counts will remain low where they’re already low,” Lewis said, but there will be intermittent cases reported, including imported cases, “which can now come from anywhere.”

With concern about and attention on mpox fading, we may now be entering a period of under-detection and under-reporting of the infection, Lewis and others suggested.

Prior to the international outbreak, a doctor examining a patient with a mpox-like rash might have safely ruled out the disease after taking a travel history. No recent travel to West and Central Africa and no close contact with someone who had returned from those regions? Must be something else. Going forward, though, travel histories will not be as helpful as an exclusionary diagnostic tool.

Many physicians still have never seen a case and may not be able to recognize the disease if confronted with an infected patient, these experts fear. The family in France became symptomatic while camping; their symptoms were mild and doctors initially wondered if their lesions were the result of mosquito bites.

Boghuma Titanji, an assistant professor of infectious diseases at Emory University, has treated people with mpox and is often quoted in the media about the disease. She has seen first-hand how this unfamiliarity can impede detection.

On a Friday in late November, a stranger from Florida contacted her via LinkedIn. He told her he was certain he had mpox. He had lesions on his penis, he was in pain, he had trouble urinating and there was blood in his urine. He’d seen three doctors; none would prescribe Tecovirimat, the mpox antiviral drug. He’d been tested but had been told the results — and any prescription that might follow — wouldn’t come till Monday. He was desperate.

Titanji reached out to colleagues for advice. One suggested the man go to a teaching hospital in Gainesville, nearly two hours from where he lived. There he was eventually admitted and treated, though even in that setting getting the diagnosis and the drug wasn’t easy.

“It’s still quite challenging for clinicians who are not familiar with monkeypox to be able to make a clinical diagnosis or to not mistake it for something else,” Titanji said.

It doesn’t help, she noted, that mpox is a “phenomenal mimic” — resembling a number of other illnesses that involve rashes. In Nigeria, one of the countries where the virus is endemic, it’s been shown that a substantial portion — nearly half — of recent illnesses diagnosed as chickenpox are actually mpox, said Ifedayo Adetifa, director general of the Nigeria Center for Disease Control.

Titanji is relieved to see the numbers of new cases declining in Western Europe and North America. But she is worried the outbreak will continue to smolder — below the radar, evading detection.

“I worry that with the attention shifting so quickly from the current outbreak, and people being very keen to turn the page, that it would again fall into the background until the next big outbreak happens,” she said. “And we’ll go back to trying to find the notes of where we left things off to pick up on it again, and start all over.”

(If another big outbreak occurs, the notes from this one may not be as detailed as future doctors would wish. Far fewer studies have been published on the mpox outbreak than on other recent disease events like the Zika outbreak of 2016 or the Covid-19 pandemic, said Nicola Low, a professor of epidemiology and public health at the Institute of Social and Preventive Medicine in Bern, Switzerland.

“We did a sort of bibliometric thing when Zika came along and said, ‘Yeah, this is just unprecedented.’ Then of course, Covid blew everything out of the water. For monkeypox, you can keep up with the literature,” Low said. “It is not capturing people’s attention in the same way.”)

The WHO’s Lewis believes some people who contract the virus may not bring themselves to the attention of medical authorities if their cases aren’t severe, preferring to sidestep stigma and avoid orders to self-isolate while they are symptomatic. “Getting to zero would require a huge level of effort. And that conversation has yet to really, fully take place,” she said.

Michael Osterholm, director of the University of Minnesota’s Center for Infectious Disease Research and Policy, was one of the experts who told STAT last July that it might be too late to contain mpox. Osterholm’s thinking changed over the summer, as he saw the effect that infection-induced immunity was having on the trajectory of the outbreak. Between immunity generated by vaccination and infection, the pool of susceptible people started to shrink, slowing transmission.

He called the one-and-done aspect of mpox infection “a game changer.” But the problem of mpox hasn’t gone away entirely, Osterholm said. “I think this will be an ongoing chronic problem with sexual transmission, but it won’t be an explosive problem.”

In some countries, some of the high-risk men are fully vaccinated now. But some will have only had one dose of vaccine. Getting people to come back for their second dose has been a challenge, some public health officials have reported. As the sense of crisis eased, so too has the drive to get vaccinated.

“And that complacency, especially in the context where we don’t have a full understanding yet exactly on how much protection and the durability of the protection that these vaccines offer, really makes me a little bit nervous about what that would mean in terms of the ability of us to see surges, even in countries where containment has been achieved,” Titanji said. “So that’s a huge question mark. I don’t know the direction in which that is going to go.”

Another factor that contributed to the slowing spread of mpox was behavioral. The gruesome reports of the worst infections led some gay and bisexual men to take steps to avoid contracting the virus. But people who work in public health know they cannot assume that the behavioral changes will persist over time. In fact, a number are already expecting infections may flare in the spring and summer, coinciding with Pride activities and other events that draw large numbers of gay men.

“Among ourselves, we were saying: Okay, probably we’ll see the results next spring and summer here in the Northern Hemisphere, when we’ll start the large events. Plus, of course, we’ll keep an eye on the Southern Hemisphere,” said Agoritsa Baka, the principal expert for emergency preparedness and response at the European Centre for Disease Prevention and Control in Stockholm.

It’s true that some portion of the at-risk gay and bisexual men will have immunity now. But the pool of people in those networks gets replenished, Baka said, as youths who are gay become sexually active.

The WHO’s European regional office has committed itself to eliminating mpox — stopping transmission of the virus within Europe. “It would need a lot of work and a lot of commitment from all of the countries,” Baka said.

Low, whose field of study is sexually transmitted infections, said she’s hopeful that mpox can be eliminated as a public health problem in some parts of the world.

“[T]here still might be sporadic cases, and there might be small outbreaks, but … generally in most countries those are going to result from imported infections. And that’s what I would like to think would still be possible,” she said.

Low acknowledged, though, that it’s not clear that all countries that have been involved in the international outbreak will be able to stop transmission, raising particular concern about the possibility of continued spread in marginalized populations, even in rich countries “where we didn’t persist enough to make sure that it was eliminated.”

She and everyone else STAT interviewed for this piece also stressed that until the global community helps endemic countries address the problem of mpox in Africa, the decline in cases will be a respite, not a resolution of the threat this virus poses.

“We’re again back to somewhat of the same situation we were in before the international outbreak,” said Adetifa, the director of the Nigeria CDC. “Everybody feels that this is now contained in the Global North. There is sort of clarity about what to do if it happens again. But I think that people are quickly forgetting that the international outbreak did not just happen overnight. Really, the evidence suggests that mpox was circulating undetected before whatever circumstances aligned to facilitate the international outbreak, especially in men who have sex with men.”

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Adetifa said Nigerian scientists are working to get a better handle on how widespread the disease has been in the country by studying blood samples. Since 2017, case counts in the country have been far higher than they were previously. It has been clear that a disease that used to occur sporadically when the animal virus spilled over into a person in a rural setting has become something that has spread person to person in some of the country’s large cities, he said.

“We have plans to do quite a bit of work to better characterize mpox serology,” Adetifa said. “Obviously, this is occurring against a backdrop where the same members of the team have to do cholera, Lassa fever, Covid, measles, and everything else that is going… . So, we often don’t have the spare capacity to move as quickly as we would like on some of these things.”

He acknowledged that countries like Nigeria are responsible for their own health security, but noted that countries are only able to respond to the extent of their capacities and health priorities.

“In the context of global health security and recognizing that a problem anywhere may ultimately become a problem everywhere, you cannot leave countries to travel at their pace for epidemic-prone pathogens,” Adetifa said. “Because what happens is that ultimately you will get affected by that pathogen if the pace of efforts to bring it under control does not go quickly enough.”

It’s not clear what the best approach is for reducing mpox cases in countries where the virus is endemic. Widespread use of vaccines would not be warranted, he said, though targeted use of the tools wealthy countries have deployed — antiviral drugs and vaccines —  would be a help. Those tools have been out of reach to date for the mpox-endemic countries.

“I think if we had had treatments and vaccines, perhaps in the early days for the early cases … that would have probably helped to bring under control the outbreak in humans,” Adetifa said.

Going forward, sharing access to mpox vaccines and drugs with all countries where the virus is transmitting could forestall even worse events with this virus, he said, “because continued circulation of the virus perhaps will provide more opportunity for it to adapt in all sorts of other ways that we do not know about.”

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