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Lessons – and mysteries – from fast-disappearing mpox

The US public health emergency declaration for mpox ended last week in America as the outbreak, which once seemed to be spiralling out of control, quietly wound down.

While not completely gone, for more than a month, the average number of daily new cases reported to the US Centres for Disease Control and Prevention (CDC) has hovered in the single digits, plummeting from an August peak of about 450 cases a day.

Still, the US led the world in cases during the 2022-23 outbreak, with more than 30 000 people being diagnosed with mpox, including 23 who died, reports CNN.

Cases are also down across Europe, the Western Pacific and Asia but are still rising in some South American countries, according to the latest data from the World Health Organisation.

When mpox went global in 2022, doctors had too few doses of a new and unproven vaccine, an untested treatment, a dearth of diagnostic testing and a difficult line to walk in their messaging, which needed to be geared to an at-risk population that has been stigmatised and ignored in public health crises before.

Experts say the outbreak has taught the world a lot about this infection, which had only occasionally been seen outside Africa.

But even with so much learned, there are lingering mysteries too – like where this virus comes from and why it suddenly began to spread from the Central and West African countries, where it’s usually found, to more than 100 other nations.

How long has it been spreading?

Before May 2022, when clusters of people with unusual rashes began appearing in clinics in the UK and Europe, the country reporting the most cases of mpox was the Democratic Republic of Congo, or DRC.

There, cases have been steadily building since the 1970s, according to a study in the CDC’s Morbidity and Mortality Weekly Report.

In the DRC, people in rural villages depend on wild animals for meat. Many mpox infections there are thought to be the result of contact with an animal to which the virus has adapted; this animal host is not known but is assumed to be a rodent.

For years, experts who studied African outbreaks observed a phenomenon known as stuttering chains of transmission: “Infections that managed to transmit themselves or be transmitted from person to person to a limited degree, a certain number of links in that chain of transmission, and then suddenly just aren’t able to sustain themselves in humans,” said Stephen Morse, an epidemiologist at Columbia University’s Mailman School of Public Health.

Informally, scientists kept track, and Morse says that for years, the record for links in a mpox chain was about four. “Traditionally, it always burned itself out,” he said.

Then the chains started getting longer. In 2017, Nigeria – which hadn’t had a confirmed case of mpox in more than four decades – suddenly saw a resurgence of the virus, with more than 200 cases reported that year.

“People have speculated maybe it was a change in the virus that allowed it to be made better-adapted to humans,” Morse said.

From 2018 through 2021, eight cases of mpox were reported outside Africa. All were in men aged 30 to 50, all had travelled from Nigeria. Three said the rashes had started in their groin area. One went on to infect a healthcare provider. Another infected two relatives.

This Nigerian outbreak helped experts realise that mpox could efficiently spread between people.

It also hinted that the infection could be sexually transmitted, but investigators couldn’t confirm this, possibly because of the stigma involved in sharing information about sexual contact.

In May 2022, UK health officials began reporting confirmed cases of mpox. One of the people had recently travelled to Nigeria, but others had not, indicating it was spreading in the community.

Later, other countries would report cases that had started even earlier, in April.
Investigators concluded mpox had been silently spreading before they caught up to it.

Declaring an emergency

In early summer, as US case numbers began to grow, the public health response bore some uncomfortable similarities to the early days of Covid-19.

Because the virus had so rarely appeared outside Africa, most doctors weren’t sure how to identify or test for it and didn’t understand all of its routes of spread.

A new vaccine was available, and the government had placed orders for it, but most doses weren’t in the United States. Beyond that, its efficacy against mpox had been studied only in animals, so no one knew whether it would work in humans.

There was an experimental treatment, Tpoxx, but it too was unproven, and doctors could get it only after filling out reams of paperwork required by the government for compassionate use.

Some just gave up. “Tpoxx was hard to get,” said Dr Jeffrey Klausner, a clinical professor of public health at the University of Southern California’s Keck School of Medicine.

“I was scrambling to find places that could prescribe it because my own institution just became a bureaucratic nightmare. So I would refer people for treatment outside my own institution so they could get treatment.”

Finally, in August, the government declared a public health emergency, allowing agencies to access money set aside for emergencies. It also allows the government to shift funds from one purpose to another to help cover costs of the response – and helped raise awareness among doctors that mpox was something to watch for.

A task force was also set up, led by Robert Fenton, from the Federal Emergency Management Agency, and Dr Demetre Daskalakis, director of the CDC’s Division of HIV and Aids Research.

Daskalakis is openly gay and sex-positive, right down to his Instagram account, which mixes suit-and-tie shots from White House briefings with photos revealing his many tattoos.

“Dr Daskalakis … really walks on water in most of the gay community, and then [Fenton is] a logistics expert… that combination of leadership was the right answer,” Klausner said.

Mpox as a sexually transmitted infection

Early on, after the CDC identified men having sex with men as being at highest risk of infection, officials warned of close physical contact. They also said people could be infected through contact with contaminated surfaces like sheets or towels.

But they stopped short of calling it a sexually transmitted infection, a move that some saw as calculated.

“This outbreak, in this time and context to Europe, United States and Australia, was definitely sexually transmitted,” said Klausner, who says many men got rashes on their genitals and that the infectious virus was cultured in semen.

Klausner believes vague descriptions about how the virus spread were intentional, to garner resources needed for the response.

“People felt that if they called it an STD, it would create stigma, and because of the stigma of the type of sex that was occurring – oral sex, anal sex, anal sex between same-sex male partners – there may not have been the same kind of federal response. So it was actually a political calculation – to garner the resources necessary for a substantial response – to be vague about how it spread.”

But this created room for misinformation and confusion, said Tony Hoang, executive director of Equality California, a nonprofit advocacy group for LGBTQ civil rights.

“I think there was a balancing dance of not wanting to create stigma, in terms of who is actually among the highest rates of transmission, without being forthright,” he said.

Hoang’s group launched its own public information campaign, combining information from the CDC on HIV and mpox. The messaging stressed that sex was the risky behaviour and explained that light brushes or touches weren’t likely to pass the infection, he said.

Klausner thinks the CDC could have done better on messaging.

“By giving vague, nonspecific information and making comments like ‘everyone’s potentially at risk’ or ‘there’s possible spread through sharing a bed, clothing or close dancing’ … that dilutes the message,” he said.

Cases came down, but why?

In July and August, when the US was reporting hundreds of new mpox cases daily, health officials were worried the virus might be here to stay.

“There were concerns of ongoing transmission which would become endemic in the US like other STIs: gonorrhoea, chlamydia, syphilis. We have not seen that occur,” said Dr Jonathan Mermin, director of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention.

“We are now seeing three to four cases a day in America, and it continues to decline. We see the possibility of getting to zero as real.”

At the peak of the outbreak, officials scrambled to vaccinate the population at highest risk – men who have sex with men – in the hopes of limiting both severity of infections and transmission. But no one was sure whether this strategy would work.

The Jynneos vaccine was approved by the US Food and Drug Administration (FDA) in 2019 to prevent mpox and smallpox in people at high risk of those infections.

Then, the plan was to bank it in the Strategic National Stockpile as a countermeasure in case smallpox was weaponised. The approval for mpox, a virus closely related to smallpox, was tacked on because the US had seen a limited outbreak of infections in 2003, tied to the importation of exotic rodents as pets.

Jynneos had passed safety tests in humans. In lab studies, it protected primates and mice from mpox infections. But researchers only learn how effective vaccines are during infectious disease outbreaks, and Jynneos has never been put through its paces during an outbreak.

“We were left with that great unknown: does this vaccine work? Is it safe in large numbers?” Mermin said.

Beyond those uncertainties, there wasn’t enough to go around, and infectious disease experts feared  a vaccine shortage might thwart any effort to stop the outbreak.

So public health officials announced a change in strategy. Instead of injecting a full dose under the skin, or subcutaneously, they would inject just one-fifth of that dose between the skin’s upper layers, or intradermally.

An early study in the trials had suggested intradermal dosing could be effective, but it was a risk. No one was sure this dose-sparing strategy would work.

Ultimately, all of these gambles appear to have paid off.

Early studies of vaccine effectiveness show that the Jynneos vaccine protected men from mpox infections. According to CDC data, people who were unvaccinated were almost 10 times as likely to be diagnosed with the infection as those who got the recommended two doses.

Men who had two doses were about 69% less likely, and men with a single dose were about 37% less likely to have an mpox infection that needed medical attention. compared with those who were unvaccinated.

Mermin says studies have since showed that the vaccine worked well no matter if were given into the skin or under the skin – another win.

Still, the vaccine is almost certainly not the entire reason cases have plunged, simply because not enough people have contracted it.

The CDC estimates that 2m people in the US are eligible for mpox vaccination. Mermin says about 700 000 have had a first dose – around 36% of the eligible population.

So it’s unlikely vaccination was the only reason for the steep decline in cases. CDC modelling suggests that behaviour change may have played a substantial role, too.

In an online survey of men who have sex with men conducted in August, half of participants said they had reduced their number of partners and one-time sexual encounters, which could cut the growth of new infections by 20% to 30%.

If that’s the case, some experts worry the US could see mpox flare up again as the weather warms.

“The party season was during the summer, during the height of the outbreak, and we’re in the dead of winter. So there’s a possibility behaviour change may not be sustained,” said Gregg Gonsalves, an epidemiologist at the Yale School of Public Health.

He added that public health officials shouldn’t make this a “mission accomplished” moment.

Work isn’t over

Mermin says it hasn’t finished with the response but intends to switch to “a ground game”. “Much of our work in the next few months will be setting up structures to make getting vaccinated easy,” he said.

Nearly 40% of mpox cases in the US were diagnosed in people who also had HIV. So the CDC will ensure Jynneos vaccines are available as a routine part of care at HIV clinics and STI clinics that offer pre-exposure prophylaxis, or PrEP, for HIV.

Mermin said officials are also going to continue to go to LGBTQ festivals and events to offer on-site vaccinations.Additionally, they’re going to study people who’ve been vaccinated and infected to see whether they remain immune – which is still
a big unknown.

Experts say that’s just one of many questions needing a closer look. Another is just how long the virus had been spreading outside Africa before the world noticed.

“We’re starting to see some data that suggests that asymptomatic infection and transmission is possible, and that will change how we how we think about this virus and and risk,” said Anne Rimoin, an epidemiologist at the Fielding School of Public Health at UCLA.

Hoang says Equality California is pushing the CDC to address continuing racial disparities in mpox vaccination and treatment, particularly in rural areas.

He’s not worried that gay men will drop their guard now that the emergency has expired.

“We’ve learned that we have to take health into our own hands, and I think we will remain vigilant as a community for this outbreak and future outbreaks.”


CDC report – Epidemiology of Human Mpox — Worldwide, 2018–2021(Open access)


CDC Data (Open access)


CNN article – Mpox is almost gone in the US, leaving lessons and mysteries in its wake


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WHO announces new name for monkeypox, first vaccines sent to Africa


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French study suggests monkeypox can spread asymptomatically


WHO declares monkeypox a global health emergency


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