The state of global mpox in 2024: new variants, rising outbreaks in Africa, and vaccine trials just starting

Two clades—and a new variant

There are two main clades of the monkeypox virus. Clade I has long been associated with East and Central Africa—especially the DRC—whereas clade II was first identified in West Africa. The clade IIb outbreak in 2022 led to more than 97 000 laboratory confirmed cases of mpox and 186 deaths, WHO reported.4 These cases reached their peak in summer 2022 and have largely subsided, though not disappeared. In July 2024 South Africa has confirmed that it saw 20 new cases of mpox, including three deaths, in the two months from 8 May to 2 July this year, all caused by subclade IIb MPXV.5

Clade Ib can cause severe lesions, says Murhula. Sometimes these lesions appear small and concentrated around people’s genitals. In other patients, however, the wounds can grow quite large—“like someone who was burned in a fire,” he explains. The town of Kamituga, in the east of the DRC, is less than a day’s drive from the neighbouring countries of Uganda, Rwanda, Burundi, and Tanzania. Workers associated with the mines often travel along such routes. Murhula expresses his concern about onward transmission of clade Ib to these nations and beyond.

The case fatality rate among patients infected by clade Ib monkeypox virus seems to be relatively low, says Murhula. “But they suffer too much,” he explains, referring to the painful lesions, as well as the conflict that can arise within families and communities over a disease that’s become highly stigmatised in the DRC. It’s associated with sex work and spousal infidelity, he says.

It’s important to recognise that mpox is frequently transmitted through sexual contact, says Michael Marks, professor of medicine at the London School of Hygiene & Tropical Medicine, UK. “Once it gets into a sexual network, that may become the dominant transmission mechanism,” he says. “In the UK we still see cases of the 2022 virus among men who have sex with men—at a very low level, but it shows that transmission can be sustained.” And the UK is far from alone: in April, for example, a total of 27 countries reported laboratory confirmed cases of mpox to WHO.6

There are indications that the 2022 clade IIb outbreak was tied to the emergence of a new, highly transmissible form of the virus (hence the name IIb, to distinguish it from clade II more generally).7 Marks says that it’s still not clear whether the clade Ib outbreak in the DRC marks the evolution of a more harmful or transmissible form of mpox. But it may present new challenges either way. Murhula’s research suggests that existing polymerase chain reaction (PCR) tests may not reliably detect traces of the clade Ib virus.

The mpox virus has a notoriously large genome, notes Cheryl Walter, a senior lecturer in microbiology at Hull York Medical School, UK. “In quite a short period of time this big, clunky DNA virus has demonstrated that it can indeed mutate,” she says. “That is quite concerning.” She adds that mpox has likely become more of a threat in recent years because immunity to the closely related smallpox virus is waning globally. WHO’s global vaccination campaign against smallpox ended in the late 1970s.

The good news

The fact that we’re picking up evidence of diverse strains of the monkeypox virus is a sign that surveillance is improving, says Lao-Tzu Allan-Blitz, associate epidemiologist at Brigham and Women’s Hospital in Boston, Massachusetts. “[The virus] has been evolving for some time and probably going unnoticed for some time,” he says.

Technically, mpox can be transmitted through close contact that isn’t sexual, but Allan-Blitz says that we should still emphasise that the disease is sexually transmitted, partly to encourage people to take appropriate precautions when engaging in sexual activity. “No disease that we classify as sexually transmitted is exclusively transmitted by sex,” he explains, “but what we’re seeing is that sexual transmission is a really important component of mpox transmission.”

The DRC’s 2022 outbreak was tackled largely thanks to vaccination programmes in developed countries. Allan-Blitz says that this arguably took “too long” in some parts of the US, however. The vaccine now available in the US is the same as that in Europe: MVA-BN (also called Jynneos, Imvanex, or Imvamune). This is a smallpox vaccine made by Bavarian Nordic that has proved effective against mpox.

In May this year WHO published its Strategic Framework for Enhancing Prevention and Control of Mpox 2024-2027.8 The document highlights improved disease surveillance and vaccination among other key tactics, and it notes how an unpublished WHO meta-analysis found that the vaccine effectiveness of MVA-BN in people at risk of mpox was 74% with a single dose and 82% with two doses pre-exposure. A newly announced phase 2 trial of the vaccine against mpox, sponsored by Bavarian Nordic, is due to begin in “one or more African countries” later in 2024.

Another smallpox vaccine, LC16m8, is available in Japan. Mugen Ujiie, chief of the travel clinic at Japan’s National Center for Global Health and Medicine, and his colleagues recently published a study describing how they had administered this vaccine to 50 healthcare workers and found good safety and seroconversion results.9 However, they didn’t track participants’ exposure to the monkeypox virus.

The Japanese government has a stockpile of this vaccine, ostensibly in case of a terrorism incident involving smallpox. Ujiie says that the quantity of vaccine available is something of a “national secret,” but he adds, “I believe LC16m8 could be helpful as an intervention for the outbreak in the DRC.” But the DRC’s government would probably have to request vaccines from Japan before any trials in the country could take place, says Ujiie.

Separately, work is being carried out on new vaccines specific to mpox. The Smart trial has received $4.9m (£3.81m; €4.52m) from the Coalition for Epidemic Preparedness Innovations (CEPI) and the Canadian Institutes of Health Research to find out if post-exposure vaccination with Bavarian Nordic’s MVA-BN vaccine could reduce the risk of secondary mpox cases—or, if a person contracts mpox, whether it could reduce their severity of illness. The initial trial of 1500 participants will begin in the DRC in September, with plans to expand to Nigeria and Uganda.10

And tests of an mRNA mpox vaccine made by Moderna are getting under way in the UK.11 Walter expects more mpox specific mRNA vaccines to be trialled in the coming years. She emphasises the importance of heightened surveillance and vaccination, both to keep infections to a minimum and to reduce the risk of new variants emerging that could cause widespread outbreaks as in 2022.

Dearth of treatment

Treatment options for mpox, however, are limited. WHO’s strategic framework mentions them only in passing. But some smallpox antivirals are currently the subject of clinical trials,12 including tecovirimat. This drug was approved for use against smallpox in the US in 2018. The Stomp trial is assessing tecovirimat’s efficacy against mpox in a cohort of more than 500 adults and children in the US.

A separate trial of tecovirimat is being conducted in the DRC. Murhula says that, for the clade Ib cases in Kamituga and nearby, doctors don’t have access to antivirals but are using other drugs, including antibiotics (ceftriaxone, cloxacillin), painkillers (tramadol, ibuprofen), and antiseptics (povidone).

Given the relatively low case fatality rate of mpox, Allan-Blitz says that there may not be much enthusiasm for developing new treatments for the disease. “I certainly think it’s worth doing, but the level of commitment to do that with something like mpox would be really hard to muster,” he says.

Meanwhile, Murhula emphasises the importance of good surveillance and controlling the spread of the disease—including without vaccines, since they’re not universally available. He also highlights the stigma around mpox in many African countries—as with many sexually transmitted diseases and particularly those associated with men who have sex with men, for instance—which could hamper efforts to engage with communities and deliver healthcare to patients with mpox.

Marks, based in the UK, hopes that trials of mpox vaccines will take place in the DRC in the next six to 12 months. “We often really focus on the risk of it coming to us—I guess that’s the problem,” he says. “You often see people selling this as a health security issue, whereas really it’s a health access and human rights issue.”

Murhula adds that the possible zoonotic reservoirs of monkeypox virus in the DRC remain unknown. Bush meat from monkeys and wild pigs, which is often sold at markets in the country, is one potential route of transmission from animals to humans, he notes, but he says that research is needed to confirm this.

And he agrees about the importance of preventive measures. “If there is no virus vaccination, we cannot stop this outbreak,” he says. “It has already escaped us.”