Monkeypox virus is increasingly improving in human transmission

Monkeypox virus is increasingly improving in human transmission

Another variant of the virus that causes Mpox could easily spread from person to person, an analysis of the pathogen's genome shows. This development could Efforts to contain the disease in Central Africa, where infections have increased sharply in the past year. Researchers are challenged to understand what is currently driving this increase.

The results suggest that the variant, known as clade Ia, can be transmitted sustainably between people - possibly through sexual contact - during an outbreak in Kinshasa, the capital of the Democratic Republic of Congo (DRC). It was previously known that the viral variant was transmitted predominantly from animals to people in Central Africa.

“We know that viruses evolve – we saw it with Ebola, we saw it with COVID-19 and we expected it to be the same with Mpox,” says Placide Mbala, head of epidemiology and global health at the National Institute for Biomedical Research in Kinshasa, who co-led the analysis. “We don’t know how far these adaptations can go, and we are collecting data to understand how this evolution occurs.”

The preliminary results, which have not yet been peer-reviewed, have been released on October 22nd in the genomic epidemiology virological discussion forum.

Mpox diversified

There are four known variants of monkeypox virus: clade Ia, Ib, IIa, and IIb (see “Quick overview of monkeypox virus variants”). Historically, Clade I viruses occurred primarily in Central Africa, while Clade II viruses occurred in West Africa.

Everything changed in the mid-2010s, when a clade II variant caused an outbreak in Nigeria. At that time, some researchers suggested before that the variant could be transmitted through sexual contact. Their insights turned out to be prescient: a similar Clade II variant, called IIb, triggered a global outbreak of Mpox in 2022, which infected more than 90,000 people and continues to this day.

Brief overview of the variants of the monkeypox virus

Clade Ia:A variant that has been spreading the virus in people in central Africa since it was first discovered in 1970. Most infections affected children, and it was known to spread from animals to humans – until recently.

Clade Ib:The variant that has caused a surge in cases in Central Africa since it was discovered in late 2023. It is known for transmission from person to person, including through sexual contact.

Clade IIa:The least studied Mpox variant. It has spread mainly in Guinea, Liberia and Côte d'Ivoire. The routes of transmission are not fully understood; There is no documented evidence of sexual transmission, but it is likely that all forms of close contact contribute to its spread.

Clade IIb:The variant responsible for the still-smoldering global outbreak of 2022. Known for human-to-human transmission, including through sexual contact. The most affected population is men who have sex with men.

Meanwhile, clade I viruses have sporadically caused infections in humans over the past 50 years - predominantly in rural regions of central Africa. But at the end of 2023 Researchers identified a rapidly growing outbreak in more densely populated urban areas in the eastern regions of the DRC, which disproportionately affected prostitutes, suggesting that this virus variant, similar to IIb, could spread easily between people.

Through genomic sequencing, it was confirmed that the variant that caused this outbreak had several key differences from other Clade I viruses, leading researchers to name it Ib. This variant has been detected in the United Kingdom, Sweden, Thailand, India, Germany and six African countries where Mpox infections have not previously been reported. The DRC was hit particularly hard: the country reported almost 36,000 suspected cases and more than 1,000 deaths from Mpox in 2024.

But now – about a year after researchers identified an outbreak of Clade Ib in eastern DRC – Clade Ia is also worrying health authorities. This variant has also increased in the western regions of the DRC and in Kinshasa. In particular, the circulation of both Ia and Ib in the capital threatens the 17 million people living there and raises the possibility of international spread of Clade I, as Kinshasa is a hub for travel.

Signs of evolution

Health authorities are using genomic sequencing tools to track the outbreak. As part of this effort, Mbala and his colleagues sequenced virus samples from infections in Kinshasa. In samples of both clade Ia and clade Ib viruses, they found a specific pattern of genetic mutations that suggests the ongoing battle between the human immune system and the virus - a pattern that would only occur with sustained human-to-human transmission.

However, this pattern did not appear in a report posted to a preprint server in August. In this study, researchers sequenced Clade Ia virus samples collected between 2018 and 2024. The researchers' failure to detect the pattern suggests it may be a recent development. “We didn't see strong signs of evolution in the rural and endemic regions of the DRC,” says Jason Kindrachuk, a virologist at the University of Manitoba in Winnipeg, Canada, who works with Mbala and contributed to both the August preprint and Virological's. “But in Kinshasa it seems like something unique is happening there.”

Clade Ia may also have the ability to spread through sexual contact: Researchers reported the first probable case of sexually transmitted Clade I Mpox last year, and another publication on the topic is forthcoming, Kindrachuk said.

Given that clade I has been circulating between animals and humans in the DRC since 1970, Kindrachuk adds that it will be important to investigate why clade Ib suddenly emerged in 2023 and why Ia led to an increase in detected infections over the past two years. "Is it because we are better at surveillance, or because we are more aware of Mpox at the community level? Is it because people are moving around more after the [COVID-19] pandemic, or because there is a greater reliance on contact with wildlife?" he asks.

For now, there will likely be no changes to plans to roll out the first doses of Mpox vaccines on the continent because of these findings, says Nicaise Ndembi, a virologist at the African Centers for Disease Control and Prevention in Addis Ababa. Health authorities are already allocating doses to regions with higher numbers of infections, regardless of the specific variant found in the region, he explains.

1. Kinganda-Lusamaki, E. et al. Preprint at medRxiv, https://doi.org/10.1101/2024.08.13.24311951 (2024).

2. Kibungu, E.M. et al. Emerg. Infect. Dis. 30, 172–176 (2024).

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