Mpox the sequel: Will it come to the U.S.?

“The fact that mpox, a cousin of a virus (smallpox) that nearly eliminated us, is resurgent in Africa and once more threatens the high-income world calls for collective shame. It should not have happened.

“It’s stupidity to think that if you fail to tackle a new outbreak in one place, it won’t appear elsewhere.”

These words from Professor Chloe Orkin, a lead researcher on the interaction between mpox and HIV, exemplify the sense of exasperation epidemiologists feel that an outbreak of mpox in Africa threatens a repeat of the one that affected the (mostly) gay community worldwide in 2022.

Let’s be clear: unlike HIV, mpox can be stopped by a vaccine, and this time round the queer community and the world at large won’t be caught so unawares.

But restricting that vaccine to the developed world risks repeating the scenario in which an outbreak in Nigeria in 2017 – the first one seen there for 38 years –  was, to quote African researchers, ‘overlooked,’ despite the fact that the virus appeared to have changed its nature.

Formerly a sporadic infection largely caught from animals in remote areas and most often lethal to children, it was now spreading through sexual contact and affecting adults. In 2022, the same viral strain appeared in higher-income countries, initially in travelers from Africa but soon in people with no connection there.

Springing apparently out of nowhere, causing over 60,000 cases and 70 deaths in the U.S. and Europe, and over 100,000 cases and 225 deaths globally outside Africa. Ninety-seven per cent of those cases were in gay/bi men and trans women.

Now scientists are worried that a different and potentially more virulent strain of mpox has changed in the same way. Widespread and timely vaccination could stop that, but at the moment the world waits uneasily to find out where the virus will jump to next.

Mpox and its different strains

Let’s take a step back and review the facts on mpox.

It’s a member of the Orthopox group. This includes smallpox (Variola), which once killed millions but is one of the few diseases abolished by vaccination. The group also includes a variety of diseases with animal hosts that can infect people, often rarely, and cause much milder symptoms. (Varicella (chicken pox/shingles), is not related to mpox: it’s in the herpes family.)

Mpox symptoms are well known now: a rash that develops into painful leaking blisters, especially on face, extremities and genitals, often accompanied by fever. Crucially, for 9-14 days after infection, before the rash appears, people may lack symptoms but can infect others.

It sometimes takes a much milder or asymptomatic form, even in vaccinated people. It can also take a much more virulent form, especially in people with severely compromised immunity, including people with untreated HIV. In the 2022 epidemic in the U.S., 80% of people whose mpox was bad enough to require hospitalization had advanced HIV, and in the current epidemic 35% of South Africans diagnosed with mpox had HIV – twice as many as the general public there.

There are two main types of mpox, which historically have rarely left their host countries in Africa. Type 2 is the one that gave rise to the 2022 epidemic. It’s endemic to western Africa, from Togo westwards to Sierra Leone. Type 1 is concentrated in the Democratic Republic of Congo (DRC) and in neighboring countries such as Gabon, Congo-Brazzaville and Cameroon.

Historically, in its guise as an animal-to-human disease mainly caught by children, type 1, with a mortality rate of 4% to 8%, has appeared more lethal than type 2, where mortality is 1.5% to 4%.

But these deaths are largely of children of subsistence-level farmers in remote forest areas far from medical help. Already, the African CDC reports, the mortality level in the new outbreak in the eastern DRC has halved to about 2%, largely because it’s among adults, many of whom are treated in hospital. And note that in the 2022 global epidemic, the death rate was little more than 0.2%.

Nonetheless, what’s happened in the DRC so far is uncannily similar to what happened in Nigeria in 2017. A huge wave of type 1 mpox has swept through remote rain-forest regions in the west of the Democratic Republic of Congo (DRC), largely ignored by the richer world. There have been about 48,000 cases and 1512 deaths (3.7%). Case numbers in Africa, though, are hard to estimate with only 18% of suspected cases tested.

But in May this year local scientists published a paper saying that mpox had arrived in an eastern province, South Kivu. It had never been seen before in this cooler, mountainous region. Furthermore, it seemed to have changed its nature.

In the original clade 1 epidemic 69% of cases were among children, and the adults were almost all rural workers – farmers and market traders. In South Kivu, while 24% of cases were still in children, 60% were in adults living in urban regions, including shanty towns and refugee camps – the DRC/Rwanda border has been wracked by civil war for 20 years. Most worryingly, 29% of those infected were female sex workers.

They genotyped a handful of confirmed cases and found to their alarm that the virus had multiple genetic jumps to become, essentially, a new strain, which they called 1b – exactly as happened in 2022 when type 2 mutated into type 2b. It had started to mutate rapidly in September 2023.

How mpox changes its spots

How did this happen? Normally, mpox changes slowly as it shuttles between animal and human hosts. This kind of change– the slow acquisition of random mutations, some of which confer survival advantage – is called ‘canonical evolution’.

In certain circumstances – and the classic way for this to happen is for humans to live in tightly-packed urban squalor – more person-to-person infections start happening and this process then jump-starts a burst of ‘non-canonical’ evolution. This means that the virus is not mutating randomly, but in direct response to the defenses thrown at it by the immune system.

Here a fascinating link to HIV has been found. The virus was mutating in order to shrug off a natural immune defense called APOBEC3. This is a human antiviral protein produced as a first line of defense against viruses. But viruses can evolve to shrug off APOBEC3.

About a century ago, a chimp virus in the same part of central Africa discovered this trick. It developed its own gene called vif – viral infectivity factor – which neutralized APOBEC3. In the process it became HIV, and the rest is history.

Now, the DRC researchers found, mpox has made the same set of ‘non-canonical’ changes against APOBEC3, in the process becoming a highly contagious STI. And now it’s done this not once but twice.

Type 1b also shows more mobility than the old type 1. Cases of 1b have now been recorded in the neighboring countries of Burundi, Rwanda, Uganda and Kenya. Meanwhile, 2b continues to bubble up sporadically – most recently in South Africa.

Will type 1b come to the U.S.?

How worried should we be? We don’t yet know. So far, only two cases of type 1b have been detected outside Africa, in Sweden and Thailand, both in travelers from Africa.

Meanwhile, type 2b continues to appear in the U.S. and Europe, but at a much lower rate than in 2022, with about eight cases a week being reported in the U.S. and three a week in most EU countries apart from Spain, always a hot-spot, with 12 a week. This contrasts with over 100 cases a day during the 2022 peak.

The difference with 2022, as we said, is that we are better prepared. Not only are a higher proportion of people at risk in the U.S. now vaccinated, but since the World Health Organization declared the type 1 and 1b outbreaks in the DRC a ‘Public Health Emergency of International Concern’, countries and companies have at least started sending mpox vaccine to the DRC. There is no reason to think the vaccine won’t work just as well against types 1 and 1b as against types 2 and 2b.

A modest 10,000 doses of the smallpox vaccine known as Jynneos in the U.S., but Imvanex in most other countries, was the first to arrive in the DRC from the U.S. on August 30, but was soon followed by a donation of 215,000 doses, partly from the European Union and partly from Jynneos manufacturers Bavarian Nordic (BN). Another 50,000 doses from the U.S. and 15,000 from BN are pledged to arrive in October and 500,000 more doses from France, Spain, Germany and Canada are promised soon. The largest donation is 3,000,000 doses from Japan of a slightly different vaccine called LC16m8. This is promised before the end of the year.

Even nearly four million doses won’t be enough to vaccinate the 99 million-and-growing population of the DRC. So African medics plan to ‘ring-vaccinate’ – to rapidly vaccinate the contacts of every diagnosed case. It’s the strategy that ultimately contained Ebola.

Get your mpox jabs now – if you haven’t already

Surely, though, enough people at risk of mpox have now been vaccinated in the U.S. to make a second epidemic in the queer community unlikely?

Well, it depends where you are which also, of course, means who you are. Two rapid modelling studies carried out by the CDC in June to see what would happen if type 1b mpox suddenly appeared in the U.S.

One that modelled its spread in families and children found that the wave of infection would swiftly die away in the less crowded conditions of the U.S.

But the one modelling infections in the gay community found that vaccination rates made all the difference. In San Francisco 75% of members of the gay community are already vaccinated, meaning that there would be virtually no chance of a second sustained mpox epidemic in the community there. Even in Chicago a 50% vaccination rate would likely be enough to stop a repeat of 2022. (Because Jynneos was originally for smallpox, we don’t know how long it lasts against mpox, but it’s likely to be many years to a lifetime.)

But some places have lower rates. In Las Vegas, with 27% vaccinated, the chance of a sustained epidemic with more than 1000 cases by the end of the year is between 40% and 60%. And in the cities with the lowest vaccination rates – Detroit with 12% and Memphis with 11% – you’re getting to a 60-75% chance of one infection sparking a local epidemic of 2,000-4,000 cases within a year.

So get vaccinated, if you haven’t already been, and don’t forget your second jab four weeks after the first. SFAF’s senior director of clinical services, Jorge Roman, MSN, FNP-BC, AAHIVS says:

“Although rates of mpox in the Bay Area continue to be very low, we recommend that all people who may be at risk or mpox receive both doses of the Jynneos mpox vaccine. Vaccines are plentiful and easily available now, from San Francisco AIDS Foundation and other City and community partners. SFAF will be administering free first and second doses of the vaccine at the upcoming Castro Street Fair on October 6 (no appointment needed). Please look for our booth outside of SFAF’s health center, Strut, at 470 Castro St.

“We are aware of the mpox health emergency in Africa, and although mpox rates in the Bay Area are currently at low levels, we know that infections rates can change or increase–sometimes rapidly. We urge our community members to learn more about mpox, protect themselves, and seek vaccination services. People experiencing symptoms that may be mpox are urged to seek medical attention.”