對在中部非洲傳播的 Ia 分支病毒株的分析顯示，持續的人際傳播指示著基因的突變。

馬克斯‧科茲洛夫 / 2024 年 10 月 30 日 / 新聞 / 自然

M（猴）痘病毒（這張彩色電子顯微照片中顯示的顆粒）正在演化。圓片來源: CDC/SPL

根據對病原體基因組的分析，導致MPOX的另一種病毒株可能很容易在人與人之間傳播。這一事態發展可能會使阻止該疾病在中部非洲傳播的努力更加複雜化，該地區的感染人數在過去一年中激增。這讓研究人員對目前推動這場激增的原因感到摸不著頭緒。

Mpox 正在迅速傳播。以下是研究者急於回答的問題

研究結果顯示，在剛果民主共和國（DRC）首都金薩沙爆發的疫情中，這種名為 Ia 分支的病毒株正在人與人之間持續傳播（可能是透過性接觸）。此前，已知該病毒株主要從中非的動物傳播給人類。

美國國家生物醫學研究所流行病學和全球衛生部門負責人普拉西德·姆巴拉 (Placide Mbala) 表示：「我們知道病毒會進化，我們在伊波拉病毒中看到過這種情況，在新冠病毒中也看到過這種情況，預計在MPOX 中也會看到這種情況。」， 「我們不知道這些適應能走多遠，我們正在收集數據以了解這種進化是如何發生的。」

研究之初步結果尚未經過同行評審，但已於 10 月 22 日在病毒學基因組流行病學討論論壇上發表。

Mpox 多樣化

猴痘病毒有四種已知變種：分支 Ia、Ib、IIa 和 IIb（參見「猴痘病毒株快速指南」）。歷史上，I型病毒主要出現在中非，II型病毒則出現在西非。

這一切在 2010 年代中期發生了變化，當時一種分支 II 病毒株在奈及利亞爆發了疫情。當時，一些研究人員認為該病毒株可能能夠透過性接觸傳播。事實證明，他們的見解是有先見之明的：一種類似的 clade II 病毒株（稱為 IIb）在 2022 年引起了全球性 MPOX 疫情爆發，已感染超過 90,000 人，並持續至今。

猴痘病毒株快速指南

Ia 分支：自 1970 年首次發現該病毒感染人類以來，該病毒株一直在中非傳播。大多數感染發生在兒童中，直到最近才知道它主要從動物傳播給人類。

Ib 分支：自 2023 年底發現以來，該菌株已導致中非病例激增。已知可在人與人之間傳播，包括透過性接觸。

IIa分支：研究最少的mpox菌株。它主要在幾內亞、賴比瑞亞和象牙海岸傳播。傳播方式尚不完全清楚；沒有性傳播的記錄證據，但所有形式的密切接觸都可能導致其傳播。

IIb分支：導致 2022 年全球疫情持續發酵的病毒株。已知可在人與人之間傳播，包括透過性接觸。受影響最大的族群是男男性行為者。

與此同時，50 多年來，第I 型病毒一直在人群中造成零星感染——主要發生在中非農村地區。但在2023 年底，研究人員發現剛果民主共和國東部地區人口較稠密的城市地區爆發了一場迅速蔓延的疫情，對性工作者的影響尤其嚴重，這顯示這種病毒株可能像IIb 一樣，很容易在人與人之間傳播。

基因組定序證實，導致這次疫情爆發的病毒株與其他第 I 分支型病毒有幾個關鍵差異，因此研究人員將其命名為 Ib。該病毒株已在英國、瑞典、泰國、印度、德國和六個以前從未報告過MPOX感染的非洲國家中被發現。剛果民主共和國受到的打擊尤其嚴重：該國報告 2024 年有近 36,000 例疑似感染病例，1,000 多人因 MPOX 死亡。

但現在——大約在研究人員在剛果民主共和國東部發現 Ib 分支爆發一年後——Ia 分支也讓衛生官員感到擔憂。剛果民主共和國西部地區和金薩沙的疫情也加劇。特別是，考慮到金薩沙是一個旅遊樞紐，Ia 和 Ib 在首都的流通會威脅到居住在那裡的 1,700 萬人，並增加了第 I 型分支在國際上傳播的可能性。

演化的跡象

衛生官員一直在使用基因組定序工具來追蹤疫情。作為努力的一部分，姆巴拉和他的同事對金薩沙感染的病毒樣本進行了基因測序。在 Ia 和 Ib 病毒分支的樣本中，他們發現了單字母基因突變的特定模式，顯示該病毒正在發生人類免疫系統和病毒之間的鬥爭－－除非人與人之間持續的傳播，否則這種模式不太可能出現。

Mpox 疫苗在非洲開始推廣：怎樣才能成功？

然而，該模式並未出現在 8 月 1 日發佈到預印本伺服器的報告中。在這項研究中，一個團隊對 2018 年至 2024 年間收集的 Ia 分支病毒樣本進行了測序。位於加拿大溫尼伯的曼尼托巴大學的病毒學家賈森·金德拉丘克 (Jason Kindrachuk) 與姆巴拉合作並共同撰寫了8 月份的病毒學預印本研究報告，他說，在剛果民主共和國更農村和地方性流行的地區，「我們沒有發現強烈的演化跡象。」，「但在金薩沙，似乎發生了一些獨特的事情。」

進化枝 Ia 也可能具有透過性接觸傳播的能力：研究人員去年報告了首例可能透過性行為傳播的分枝 I 型mpox 病例，另一篇此類研究發表即將出版，Kindrachuk 說。

由於自1970 年以來，分支I型一直在剛果民主共和國的動物和人類之間傳播，Kindrachuk 補充說道，去調查為什麼分支型Ib 會在2023 年突然出現，以及為什麼Ia 導致在過去兩年間檢測到的感染數量激增，這一點非常重要。 「是因為我們更擅長於監視，還是因為我們對社區層面的MPOX更加地了解？是因為 [COVID-19]大流行之後人們的活動量增加了，還是因為人們更加依賴於與野生動物的接觸？」，他問道。

位於亞的斯亞貝巴的非洲疾病管制與預防中心的病毒學家 Nicaise Ndembi 表示，鑑於這些發現，目前推出非洲第一劑mpox疫苗的計畫不太可能改變。他說，衛生官員已經將劑量分配給感染人數較多的地區，無論該地區發現的特定的病毒株為何。

自然 635, 13-14 (2024)

doi：https://doi.org/10.1038/d41586-024-03531-x

參考文獻：

1. Kinganda-Lusamaki,E. et al.。預印本發表於 medRxiv，https://doi.org/10.1101/2024.08.13.24311951 (2024)。

2. Kibungu, E. M. et al. 《新興感染症》30, 172–176 (2024)。

Monkeypox virus keeps getting better at spreading among humans

Analysis of a clade Ia strain of the virus circulating in Central Africa shows genetic mutations indicative of sustained human-to-human spread.

Max Kozlov / 30 October 2024 /  NEWS / Nature

The monkeypox virus (particles shown in this coloured electron micrograph) is evolving.

Credit: CDC/SPL

Yet another strain of the virus that causes mpox might be readily spreading from person to person, according to an analysis of the pathogen’s genome. This development could further complicate efforts to halt the spread of the disease in Central Africa, which has seen a surge in infections over the past year. And it has left researchers scratching their heads over what is currently driving this surge.

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

The findings hint that the strain, called clade Ia, is spreading in a sustained fashion between people — possibly through sexual contact — in an outbreak in Kinshasa, the capital of the Democratic Republic of the Congo (DRC). Previously, the viral variant was known to transmit predominantly from animals to humans in Central Africa.

“We know that viruses evolve — we have seen it with Ebola, we have seen it with COVID and we expected to see it with mpox as well,” says Placide Mbala, head of epidemiology and global health at the National Institute of Biomedical Research in Kinshasa, who co-led the analysis. “We don’t know how far these adaptations can go, and we are gathering data to understand how this evolution is occurring.”

The preliminary results, which have not yet been peer-reviewed, were posted on 22 October to the genomic-epidemiology discussion forum Virological.

Mpox diversifies

There are four known variants of the monkeypox virus: clades Ia, Ib, IIa and IIb (see ‘Quick guide to the strains of monkeypox virus’). Historically, clade I viruses have appeared mostly in Central Africa, and clade II viruses have cropped up in West Africa.

This all changed in the mid-2010s, when a clade II strain sparked an outbreak in Nigeria. At the time, some researchers suggested that the variant might be capable of transmission through sexual contact. Their insights proved prescient: a similar clade II strain, called IIb, sparked a global outbreak of mpox in 2022 that has infected more than 90,000 people and continues today.

Quick guide to the strains of monkeypox virus

Clade Ia: a strain that has been spreading in Central Africa since the virus was first discovered to infect humans in 1970. Most infections have been in children, and it was known to mainly transmit from animal to human — until recently.

Clade Ib: the strain that has caused a surge of cases in Central Africa since its discovery in late 2023. Known to spread from person to person, including through sexual contact.

Clade IIa: the least-studied mpox strain. It has mainly spread in Guinea, Liberia and Côte d’Ivoire. Modes 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 strain responsible for the still-simmering 2022 global outbreak. Known to spread from person to person, including through sexual contact. Most affected population has been men who have sex with men.

Meanwhile, clade I viruses have caused sporadic infections in people for more than 50 years — largely in rural regions of Central Africa. But in late 2023, researchers identified a rapidly growing outbreak in more densely populated, urban areas in eastern regions of the DRC that disproportionately affected sex workers, suggesting that this strain of the virus could, like IIb, spread readily between people.

Genomic sequencing confirmed that the variant causing this outbreak contained several key differences from other clade I viruses, leading researchers to name it Ib. This strain has been detected in the United Kingdom, Sweden, Thailand, India, Germany and six African countries that had never reported mpox infections before. The DRC has been hit particularly hard: the country has reported nearly 36,000 suspected infections and more than 1,000 deaths from mpox in 2024.

But now — about one year after researchers detected an outbreak of clade Ib in eastern DRC — clade Ia is worrying health officials, too. The strain has also been on the rise in western regions of the DRC and in Kinshasa. In particular, having both Ia and Ib circulating in the capital city threatens the 17 million people living there and raises the possibility of clade I spreading internationally, given that Kinshasa is a travel hub.

Signs of evolution

Health officials have been using genomic-sequencing tools to track the outbreak. As part of the effort, Mbala and his colleagues sequenced virus samples from infections in Kinshasa. In samples of both the clade Ia and Ib virus, they found a specific pattern of single-letter genetic mutations indicative of the ongoing battle between the human immune system and the virus — a pattern that would be unlikely to appear unless there was sustained human-to-human spread.

Mpox vaccine roll-out begins in Africa: what will success look like?

However, the pattern did not show up in a report posted to a preprint server in August. In that study, a team sequenced clade Ia virus samples collected between 2018 and 2024. That the researchers didn’t spot the pattern suggests that it might be a recent development. “We didn’t pick up on strong signs of evolution” in the more rural and endemic regions of the DRC, says Jason Kindrachuk, a virologist at the University of Manitoba in Winnipeg, Canada, who collaborates with Mbala and co-authored the August preprint as well as the Virological one. “But in Kinshasa, it seems that there is something unique going on.”

Clade Ia might 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 such publication is forthcoming, Kindrachuk says.

Given that clade I has been circulating between animals and people in the DRC since 1970, Kindrachuk adds that it will be important to investigate why clade Ib suddenly emerged in 2023, and why Ia has caused a surge in the number of detected infections in the past two years. “Is it because we’re better at surveillance, or because we’re more conscious of mpox at the community level? Is it because people have been moving around more after the [COVID-19] pandemic, or because there’s been a greater reliance on contact with wildlife?” he asks.

For now, plans to roll out the continent’s first doses of mpox vaccines are unlikely to change in light of these findings, says Nicaise Ndembi, a virologist at the Africa Centres for Disease Control and Prevention in Addis Ababa. Health officials have already been allocating doses to regions that have a higher number of infections, regardless of the specific strain found in the area, he says.

Nature 635, 13-14 (2024)

doi: https://doi.org/10.1038/d41586-024-03531-x

References

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).