Mpox is spreading rapidly. Here are the questions researchers are racing to answer – Nature.com

Monkeypox virus particles (shown in this coloured electron micrograph) can spread through close contact with people and animals.Credit: NIAID/Science Photo Library

When the World Health Organization (WHO) declared a public-health emergency over mpox earlier this month, it was because a concerning form of the virus that causes the disease had spread to multiple African countries where it had never been seen before. Since then, two people travelling to Africa one from Sweden and one from Thailand have become infected with that type of virus, called clade 1b, and brought it back to their countries.

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Although researchers have known about the current outbreak since late last year, the need for answers about it is now more pressing than ever. The Democratic Republic of the Congo (DRC) in Central Africa has spent decades grappling with clade I virus a lineage to which Ib belongs. But in the past, clade I infections usually arose when a person came into contact with wild animals, and outbreaks would fizzle.

Clade Ib seems different, and is spreading largely through human contact, including through sex. Nearly 18,000 cases of mpox, many of them among children, and at least 600 deaths have been reported this year in the DRC alone.

How does this emergency compare with one declared in 2022, when mpox cases spread across the globe? How is this virus behaving compared with the version that triggered that outbreak, a type called clade II? And will Africa be able to rein this one in? Nature talks with researchers about information they are rushing to gather.

Its hard to determine, says Jason Kindrachuk, a virologist at the University of Manitoba in Winnipeg, Canada. He says that the DRC is experiencing two outbreaks simultaneously. The clade I virus, which has been endemic in forested regions of the DRC for decades, circulates in rural regions where people get it from animals. That clade was renamed Ia after the discovery of clade Ib. Animal studies suggest that clade I is deadlier than clade II1 but Kindrachuk says its hard to speculate what that means for humans at this point.

Even when not fatal, mpox can trigger fevers, aches and painful fluid-filled skin lesions.

Growing mpox outbreak prompts WHO to declare global health emergency

Although many reports claim that 10% of clade I infections in humans are fatal, infectious disease specialist Laurens Liesenborghs at the Institute of Tropical Medicine in Antwerp, Belgium, doubts that this figure is accurate. Even the WHOs latest estimate of a 3.5% fatality rate for people with mpox in the DRC might be high.

There are many reasons fatality estimates might be unreliable, Liesenborghs says. For one, surveillance data captures only the most severe cases; many people who are less ill might not seek care at hospitals or through physicians, so their infections go unreported.

Another factor that can confound fatality rates is a secondary health condition. For example, people living with HIV who represent a significant proportion of the population in many African countries die from mpox at twice the rate of people who do not have compromised immune systems, especially if their HIV is untreated2. And the high death rate among children under age 5 could be partly due to malnutrition, which is common among kids in rural parts of the DRC, Liesenborghs says.

The clade 1b virus has garnered particular attention because epidemiological data suggest that it transmits more readily between people than previous strains, including through sexual activity, while clade Ia mostly comes from animals. An analysis published ahead of peer review last week to the preprint server medRxiv3 shows that clade Ibs genome contains genetic mutations that seem to have been induced by the human immune system, suggesting that it has been in humans for some time. Clade Ia genomes have fewer of these mutations.

But Liesenborghs says that the mutations and clades might not be the most important factor in understanding how the monkeypox virus spreads. Although distinguishing Ia from Ib is useful in tracking the disease, he says, severity and transmissibility of disease could be more affected by the region where the virus is circulating and the people there. Clade Ia, for instance, seems to be more common in sparsely populated rural regions where it is less likely to spread far. Clade Ib is cropping up in densely populated areas and spreading more readily.

Jean Nachega, an infectious disease physician at the University of Pittsburgh in Pennsylvania, says that scientists dont understand many aspects of mpox transmission they havent even determined which animal serves as a reservoir for the virus in the wild, although rodents are able to carry it. We have to be very humble, Nachega says.

Just as was the case during the COVID-19 pandemic, health experts are looking to vaccines to help curb this mpox outbreak. Although there are no vaccines designed specifically against the monkeypox virus, there are vaccines proven to ward off a related virus the one that causes smallpox. Two currently exist. Jynneos, made by Bavarian Nordic in Hellerup, Denmark, contains a type of poxvirus that cant replicate but can trigger an immune response. LC16m8, made by KM Biologics in Kumamoto, Japan, contains a live but weakened version of a different poxvirus strain.

Hopes dashed for drug aimed at monkeypox virus spreading in Africa

Still, its unclear how effective these smallpox vaccines are against mpox generally. Dimie Ogoina, an infectious disease specialist at Niger Delta University in Wilberforce Island, Nigeria, points out that vaccines have been tested only against clade II virus in European and American populations because these shots were distributed by wealthy nations during the global outbreak that started in 2022. And those recipients were primarily young, healthy men who have sex with men, the population that drove that outbreak. One study in the United States found that one dose of Jynneos was 80% effective at preventing the disease in people at risk while two doses was 82% effective4; the WHO recommends getting both jabs.

People in Africa infected with either the clade Ia or 1b virus especially children and those with compromised immune systems might respond differently, although one study in the DRC found that the Jynneos vaccine could generally raise antibodies against mpox in about 1,000 healthcare workers who received it5.

But researchers are trying to fill in some data gaps. A team in the DRC is about to launch a clinical trial of Jynneos in people who have come into close contact with the monkeypox virus but have not shown symptoms to see whether it can prevent future infection, or improve outcomes if an infection arises.

Mpox vaccines have so far been largely unavailable in Africa, but several wealthy countries have pledged to donate doses to the DRC and other affected African nations. The United States has offered 50,000 Jynneos doses from its national stockpile, and the European Union has ordered 175,000, with individual member countries pledging additional doses and Bavarian Nordic adding another 40,000. Japan has offered 3.5 million doses of LC16m8 (which requires only one jab instead of two).

Monkeypox in Africa: the science the world ignored

None of them has arrived yet, though, says Espoir Bwenge Malembaka, an epidemiologist at the Catholic University of Bukavu in the DRC. Low- and middle-income nations that rely on vaccine donations cannot receive them until the WHO has determined that the jabs are safe and effective. And so far, the WHO has not given its thumbs up. It is evaluating additional data that it received from vaccine manufacturers, delaying donors ability to send the vaccines.

Even when the vaccines arrive, Bwenge Malembaka says, its really a drop in the bucket. The African Centres for Disease Control and Prevention in Addis Ababa, Ethiopia, estimates that 10 million doses are needed to rein in the outbreak.

Bwenge Malembaka says that the uncertainty over vaccine arrival has made it difficult for the government to form a distribution plan. I don't know how one can go about this kind of challenge, he says. Bwenge Malembaka suspects children are likely to receive doses first, because they are highly vulnerable to clade I, but officials havent decided which regions to target. Its also unclear how the government would prioritize other vulnerable populations such as sex workers, who have been affected by clade Ib. Their profession is criminalized in the DRC, so they might not be able to come forwards for treatment.

Researchers lament that public-health organizations didnt provide vaccines and other resources as soon as the clade I outbreak was identified, especially given lessons learned from the 2022 global mpox outbreak. The opportunity was there a couple months ago to cut this transmission chain, but resources werent available, Liesenborghs says. Now it will be more challenging to tackle this outbreak, and the population at risk is much broader.

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Mpox is spreading rapidly. Here are the questions researchers are racing to answer - Nature.com