Even as mpox vaccines reach Africa, questions remain about the virus

Congo is at the center of a surge in mpox (formerly known as monkeypox) cases that prompted a new public health emergency declaration by the WHO.SN: 14.8.24). The sometimes deadly disease has long been a problem in the region, causing symptoms including fever, muscle aches and a characteristic rash that looks like a pimple or blister.

Since the first mpox case in 1970, most cases have occurred sporadically in young children, usually after exposure to wild animals such as rodents or primates infected with the virus, and have sometimes caused small outbreaks (SN: 25/6/22). But Congo has seen a steady rise in cases over the past decade, driven by viruses belonging to a subgroup called clade I. Behind the latest health emergency are clade I versions that spread person-to-person in numbers in increasing countries, including through sexuality networks.

“As scientists, we are not surprised [that this is happening] because we’ve been ringing the bell for some time,” says Jean Nachega, an epidemiologist at the University of Pittsburgh. “But it seems not many people were listening.” Scientists are trying to catch up on lost decades of vaccine, drug and diagnostic research for a disease long neglected.

The first mpox-related public health emergency that hit the Americas and Europe hard in 2022—caused by viruses from another branch of the family tree called clade II—eventually faded and officially ended in May 2023 as global cases declined. But few resources reached Africa, and the spread of the virus there was not resolved. Now, a new group called clade Ib has emerged in the Congo that seems more capable of easily spreading among humans.

“Viruses thrive on opportunity,” says Boghuma Titanji, an infectious disease physician at Emory University School of Medicine in Atlanta. As viruses spread, they can pick up genetic changes that help them adapt in ways that endanger humans. “Do we really have to wait for a new variant to emerge before we, all of a sudden, play again with a public health emergency declaration to respond to [mpox]when we could have done this in [2022]?”

In the wake of the recent public health emergency declaration, countries including Japan, Spain and the United States are pledging vaccine donations to affected countries. Meanwhile, nearly 6,000 mpox cases have been confirmed in 15 African countries since September 13, with tens of thousands more suspected and 724 people dead. Here’s what we know so far about the latest mpox outbreaks and the viruses that cause them, and what researchers still hope to learn.

What are clade I and clade II? How are they different?

When talking about viruses, “clade” refers to groups of close relatives that cluster together in the viral family tree. The viruses that cause mpox can be classified into clades I and II; each circulating in different parts of Africa.

Historically, class II viruses jumped from animals to humans in parts of West Africa, including Sierra Leone and Nigeria. But around 2014, a clade II virus began to spread among humans, the researchers reported in a preprint posted June 19 on medRxiv.org that has not yet been peer-reviewed. Public health officials first detected human cases in 2017. Five years later, in 2022, the outbreak went global, spreading primarily through the sexual networks of men who have sex with men (SN: 22.7.22). Clade II viruses still circulate in Nigeria and cause sporadic cases elsewhere.

Two groups of clade I viruses, called clade Ia and clade Ib, both commonly found in the Congo, are the focus of the new public health emergency. Clade Ia mainly affects children. That’s partly because children like to play in the woods, where they can come into contact with infected animals, Nachega says, although there is occasional transmission between people. In 2023 and 2024, clade Ia cases also appeared in the Central African Republic and the Republic of Congo.

Then, in September 2023, there was an outbreak of mpox with human-to-human transmission in Kamituga, a mining area in eastern Congo. Like those caused by clade II viruses, the outbreak was linked to sexual contact, this time involving sex workers and their clients. The new viral club after the outbreak, which Nachega and colleagues named clade Ib, has mutations that indicate human-to-human transmission, the team reported June 13 in Nature Medicine. “It was the first scientific confirmation that something new happened with this virus,” says Nachega.

To date, clade Ib viruses have spread to four of Congo’s neighboring countries—Burundi, Kenya, Rwanda, and Uganda—and some travel-related cases have emerged in Sweden and Thailand. Spread also appears to have extended beyond sexual networks to move through families, likely through close contact. In Burundi, about 30 percent of confirmed cases since August 17 have been in children under 5.

According to the WHO, clade I viruses can be more severe and deadly than clade II versions. But the data is unclear. Because the clades affect different populations, it’s possible that factors such as age or the quality of health care blur the picture, making the disease appear deadlier in some countries than in others.

Why is mpox spreading so widely now compared to previous outbreaks?

After the WHO declared smallpox, a closely related virus, eradicated in 1980 and discontinued vaccinations, people have become more susceptible to mpox outbreaks over time. Now, with the immunity that once protected against both viruses declining in Africa and around the globe, mpox cases are on the rise.

But researchers have a host of questions about how specifically viruses Ia and Ib are spreading.

For example, more than half of the 5,000 confirmed mpox cases in Congo since Sept. 5 have been among children under the age of 15, according to the African Centers for Disease Control and Prevention. While clade Ib has hit adults hard, children in this age group have faced worse outcomes than adults after being infected with viruses from either class. It’s unclear how many cases are in infants, young children or teenagers, and it’s possible that different activities are behind the spread of the virus in each group, Titanji says. Caregivers can expose young children through close contact while holding babies. Older children can be exposed when they work in mines and are in contact with other adults.

Some transmission can occur through respiratory droplets that are released through speech or breathing. Although most transmission occurs through close contact, overcrowded households, where children come together with other family members, can provide multiple routes for the virus to spread among many people.

“If you don’t understand these transmission dynamics, it makes it harder to predict” what might happen when the virus jumps to another country or continent where lifestyles change, Titanji says. If there were an outbreak outside Central Africa, for example, “would we see a disproportionate impact on children?”

The virus is also spreading through sexual networks among adults, says Titanji. She would like to know if the virus hangs out in certain parts of the body, making some forms of contact more dangerous than others, or if people can transmit the virus to others even when they have no symptoms.

Are vaccines essential to control the spread of the virus?

Vaccines are among the best tools available. The Africa CDC has said the continent needs about 10 million doses of vaccine to bring mpox outbreaks under control. But given the previous difficulties in getting the shots in hand, and the obstacles to producing sufficient doses, this is a difficult hurdle to meet.

Also, “we still need hard data” to understand how effective existing smallpox vaccines are in protecting people from clade Ib viruses, Nachega says. Researchers are developing mpox-specific vaccines (although they are not yet ready to be tested in humans, so they are not useful in the current outbreak). A candidate outperformed the Jynneos smallpox vaccine in protecting rhesus macaques from mpox, researchers reported Sept. 4 in Cell. Vaccinated animals had fewer lesions and fewer days of symptoms than those given Jynneos or placebo.

“We cannot have another vaccine-based strategy,” said Ayoade Alakija, an infectious disease physician and chair of the African Union Vaccine Delivery Alliance, during an August 28 briefing on mpox at the Regional Committee Meeting of WHO for Africa. “We have to do primary health care. We have to do the basics. It’s not just about vaccines.”

There are a handful of drugs to treat smallpox, for example. But it is unclear how effective antivirals are against mpox. A recent test of the drug tecovirimat showed that the rashes of treated people infected with clade I viruses did not resolve any faster than those given a placebo.

Helping people understand how to change behavior in ways that help curb transmission is also important, Titanji says. During the 2022 outbreak, campaigners are pushing messages that the virus that causes mpox is spreading among men who have sex with men and that restricting sexual encounters can protect people from getting mpox. “And it worked,” says Titanji.

However, without enough shots to protect high-risk groups in affected countries, the outbreak will likely continue for some time, Nachega says. “No one is safe until Africa is safe.”