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Amid a new surge of mpox in Africa, the spread of the more deadly clade I subtype, and a rising number of mpox cases in children, clinicians are struggling to understand this complex and evolving global situation.

In this latest major wave originating in the Democratic Republic of the Congo (DRC), more than have occurred in the DRC, for a case fatality rate of approximately 5%.

This Outbreak Is Different

"What we are witnessing in Africa now is different from the global outbreak in 2022," Dimie Ogoina, MBBS, chair of the World Health Organization's (WHO) mpox emergency committee, said in a .

While the 2022 outbreak occurred overwhelmingly among gay and bisexual men, mpox in Africa is now being spread not only by sexual contact, but also by close person-to-person contact in certain parts of the DRC -- most notably to children.

Also, the current outbreak in the DRC is more widespread than previous outbreaks. The clade I variant has now spread to Burundi, Central African Republic, Republic of the Congo, Rwanda, and Uganda, among others.

In August, the WHO declared its second global mpox emergency in response to this spread.

The agency declared the first global mpox emergency in July 2022, as a multi-country outbreak originating from Nigeria rapidly spread to other countries where the virus had never been seen before, including the U.S.

The WHO withdrew that emergency in May 2023, but by that time there had been more than .

Mpox is in the Orthopoxvirus genus in the Poxviridae family of viruses that includes variola, cowpox, and vaccinia viruses, among others. There are two distinct clades of the virus: clade I, with genetically different subclades Ia and Ib; and clade II, with subclades IIa and IIb. Clade I and its subvariants causes more severe disease than clade II.

"The situation is complicated by the detection of a new variant -- clade Ib -- in the DRC," Jay Varma, MD, an expert in global health and chief medical officer of SIGA Technologies in New York City, told MedPage Today.

"This variant was first identified in men visiting female sex workers, and researchers are concerned it may spread more easily through heterosexual sex, although this has not yet been confirmed," he explained.

Of particular concern, two cases of the clade Ib variant have recently been reported in and , both occurring in people who had traveled to Africa.

Is Clade Ib More Deadly?

"We do not believe that clade Ib causes more severe illness or death than clade I," Varma said. "However, there have not been enough patients studied to draw firm conclusions."

Prior to 2022, mpox outbreaks in Central and West Africa, primarily caused by the clade II variant, appeared to result in relatively mild disease, but more severe disease associated with the clade I subtype, was known to occur in parts of the DRC.

The overall case fatality rate of the current clade I outbreak is about 4.6% to 5%, but some regions have reported . In comparison, the case fatality rate during the mpox outbreak of 2022, driven predominantly by clade II, was just 0.18%.

Is clade Ib more transmissible than clade II? So far, there is no definitive answer to that question. other than clade subtype, such as the region where the virus is circulating or population density.

DRC Cases Among Children

Notably, in the DRC in this current surge have occurred in children ages 15 years and younger. Young children -- ages 12 to 59 months -- have accounted for 28% of all suspected cases.

"Public health agencies have not yet fully explained why so many children have been infected in the DRC," Varma commented.

"The most likely explanation is that children are being infected by coming into contact with the skin of infected people and/or surfaces contaminated by mpox in homes and schools, where there is crowding, minimal clothing coverage, and poor hygiene, particularly surface cleaning," he explained.

What About Mpox in the U.S.?

Since the global outbreak began in 2022, over 32,000 cases of clade II mpox have been reported in the U.S., resulting in 58 deaths. At the height of the outbreak, about were being reported.

To date, there have been no reported cases of clade I in the U.S.

But mpox is still circulating. According to CDC data, there have been a total of in 2024 alone versus 791 in 2023, with an average of about 59 cases per week.

In the U.S., most new cases of mpox occur among gay or bisexual men. The majority of infected individuals of the modified vaccinia Ankara-Bavarian Nordic (Jynneos) mpox vaccine.

The CDC still states that the , due to the fact that there are a limited number of travelers coming from affected areas. However, that risk could change if more cases emerge outside of Africa.

According to the agency, the U.S. has robust mpox testing capacities in state and commercial laboratories that can accurately identify different clades. Also, some communities, as well as airports, are to detect the early presence of mpox.

The CDC has developed and clinical guidance for the .

There are now two FDA-approved vaccines against mpox -- and ACAM2000. A found that infection after receipt of two doses occurred in fewer than 1% of fully vaccinated persons.

"We are likely to learn more about mpox in the coming months," Varma emphasized, and he recommended staying informed of any CDC and health agency updates. "It is crucial to be prepared to adapt to new information."

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