猴痘爆發：研究人員提出的 4 個關鍵問題
研究人員正在競相了解最新的猴痘爆發——從起源到能否得到控制。
資料來源：Nature / NEWS EXPLAINER / 2022 年 5 月 27 日
猴痘病毒是一種雙鏈 DNA 病毒，它會感染細胞，然後在細胞質內復制。
圖片來源：UK Health Security Agency/Science Photo Library
自公共衛生當局在英國確認一例猴痘病例以來已經過去了三週。從那時起，至少 20 個非屬非洲國家出現了 400 多例確診或疑似病例，包括加拿大、葡萄牙、西班牙和英國——這是非洲以外有史以來最大規模的疫情。這種情況讓科學家們保持警惕，因為猴痘病毒已經在多個國家的不同人群中出現，並且許多群集之間並沒有明顯的聯繫，這增加了病毒未被發現之本地傳播的可能性。
「我們需要迅速果斷地採取行動，但仍有很多東西需要學習」，加州大學洛杉磯分校的流行病學家 Anne Rimoin 說，她在剛果民主共和國研究猴痘已有超過十年。
《自然》期刊概述了研究人員正在競相回答的有關最近爆發的一些關鍵問題。
當前的疫情是如何開始的？
自最近一次疫情爆發以來，研究人員對從比利時、法國、德國、葡萄牙和美國等國家的猴痘患者身上收集的病毒基因組進行了測序。到目前為止，他們獲得的最重要的見解是，每個序列都非常類似於在西非發現的猴痘病毒株。與在中非發現的死亡率高達 10% 的毒株相比，這種毒株的致死率較低——在貧困的農村人口中，它的死亡率低於 1%。
猴痘走向全球：科學家為何保持警惕
關於疫情可能是如何開始的線索也出現了。儘管研究人員需要更多數據來證實他們的懷疑，但他們迄今為止評估的序列幾乎相同，這顯示最近在非洲以外的疫情可能都與經過徹底流行病學調查的單一病例有關。
目前的序列與 2018 年和 2019 年在非洲以外出現的少數猴痘病例的序列最相似，這些病例與西非旅行有關。最簡單的解釋是，今年出現首例非屬非洲病例的人（尚未確定身份）是透過在訪問非洲類似地區時與攜帶病毒的動物或人類接觸而感染的，馬里蘭州貝塞斯達國家過敏和傳染病研究所的病毒學家伯尼·莫斯 (Bernie Moss) 說。
但不能排除其他解釋，紐約市西奈山伊坎醫學院的病毒學家 Gustavo Palacios 說。該病毒有可能已經在非洲以外的人類或動物中傳播，但未被發現，是在早期爆發期間引入的。然而，這種假設不太可能，因為猴痘病毒通常會在人體上引起明顯的損傷——這可能會引起醫生的注意。
病毒的基因變化可以解釋最近的爆發嗎？
阿拉巴馬大學伯明翰分校研究痘病毒進化的計算病毒學家 Elliot Lefkowitz 說，要了解這種病毒在非洲以外前所未有的傳播是否有遺傳基礎將是非常困難的。與西非菌株相比，在他們發現兩者之間存在差異 17 年多之後，研究人員仍在努力準確地確定哪些基因導致中非菌株的毒力和傳播性更高。
天花和其他病毒比懷疑更早地困擾著人類
Lefkowitz 說，其中一個原因是痘病毒基因組包含許多謎團。與許多其他病毒相比，猴痘基因組是巨大的——它是 SARS-CoV-2 冠狀病毒基因組的六倍多。這意味著它們至少「難以分析六倍」，北卡羅來納州格林維爾東卡羅來納大學的病毒學家雷切爾·羅珀 (Rachel Roper) 說。
Palacios 說，另一個原因是很少有資源專門用於非洲的基因組監測工作，多年來猴痘一直是公共衛生問題。他說，所以病毒學家現在有點盲目，因為他們幾乎沒有原存之序列可以比較新的猴痘序列。他補充說，資助機構沒有注意到科學家們十多年來一直警告可能會進一步爆發猴痘。
奈及利亞疾病控制中心負責人 Ifedayo Adetifa 說，與他交談過的非洲病毒學家對他們多年來一直在努力籌集資金和發表關於猴痘的研究表示憤怒——但現在它已經蔓延到非洲大陸以外，公共衛生世界各地的權威機構似乎突然更感興趣了。
Palacios說，要了解病毒如何進化，對動物體內的病毒進行測序也很有用。眾所周知，這種病毒會感染動物——主要是松鼠和老鼠等囓齒動物——但科學家們尚未在非洲受影響地區發現它的天然動物宿主。
能控制住疫情嗎？
自從當前疫情爆發以來，一些國家一直在採購天花疫苗，這些疫苗被認為對猴痘非常有效，因為這些病毒是相關的。根據美國疾病中心的數據，與針對 COVID-19 的疫苗需要兩週時間才能提供全面保護不同，由於病毒的潛伏期長，天花疫苗被認為如果在接觸猴痘後四天內接種可以防止猴痘感染，根據喬治亞州亞特蘭大的疾病控制和預防中心 (CDC) 表示。
解開美國最大的冠狀病毒爆發的競賽
如果部署，這些疫苗可能會使用「環形疫苗接種」策略應用，該策略將為感染者的密切接觸者接種疫苗。領導 CDC 痘病毒小組的流行病學家 Andrea McCollum 說，該機構尚未部署環形疫苗接種策略。但與此同時，美國有線電視新聞網報導稱，美國計畫為一些治療感染者的醫護人員提供天花疫苗。 Rimoin 說，除了感染者的密切接觸者之外，還可能值得考慮為感染風險較高的人群接種疫苗。
即使公共衛生官員在當前疫情期間阻止了猴痘在人類中的傳播，病毒學家也擔心該病毒可能會再次傳播到動物身上。在動物體內擁有新的病毒宿主會增加病毒一次又一次地傳播給人類的可能性，包括在沒有任何已知的病毒動物宿主的國家。 5 月 23 日，歐洲疾病預防控制中心強調了這種可能性，但認為這種可能性「非常低」。儘管如此，歐洲衛生官員仍強烈建議將屬於猴痘確診病例的倉鼠和豚鼠等寵物囓齒動物隔離並在政府設施中進行監測或實施安樂死，以避免溢出的可能性。
儘管風險很低，但Moss表示，主要擔心的是科學家們常常是直到為時已晚時才知道這種溢出事件是否發生，因為受感染的動物通常不會表現出與人類相同的明顯症狀。
與以前的爆發相比，現在的病毒傳播方式是否不同？
已知猴痘病毒透過與受感染的人或動物的病灶、體液和呼吸道飛沫密切接觸而傳播。但據美聯社報導，衛生官員一直在研究西班牙和比利時兩場狂歡中的性活動是否是猴痘傳播的驅動因素，這引發了人們對該病毒已經進化為更擅長於性傳播的猜測。
草原犬鼠模型為解決猴痘病毒提供了希望
然而，與性活動有關的病例並不意味著病毒更具傳染性或透過性傳播——只是病毒很容易透過密切接觸傳播，Rimoin 說。 Roper 說，與 SARS-CoV-2 不同，它被認為不會在物體表面逗留很長時間，但痘病毒可以在體外存活很長時間，這使得床單和門把手等物品之表面成為潛在的傳播載體。
儘管衛生官員注意到許多病例發生在男男間性行為者 (MSM) 中，但 Rimoin 強調，該病毒在 MSM 群體中傳播的最可能的解釋是該病毒是偶然引入社群的，並且一直持續在那裡蔓延。
McCollum說，所有對猴痘的新關注都暴露了科學家對該病毒的了解程度。「當一切塵埃落定後，我認為我們將不得不去認真思考研究之優先順序在哪裡」，她說。
doi：https://doi.org/10.1038/d41586-022-01493-6
Monkeypox outbreaks: 4 key questions researchers have
Researchers are racing to understand the latest monkeypox outbreaks — from their origins to whether they can be contained.
Nature / NEWS EXPLAINER / 27 May 2022
Monkeypox virus is a double-stranded DNA virus that infects cells and then replicates inside their cytoplasm.Credit: UK Health Security Agency/Science Photo Library
It’s been three weeks since public-health authorities confirmed a case of monkeypox in the United Kingdom. Since then, more than 400 confirmed or suspected cases have emerged in at least 20 non-African nations, including Canada, Portugal, Spain and the United Kingdom — the largest outbreak ever outside of Africa. The situation has scientists on alert because the monkeypox virus has emerged in separate populations across multiple countries, and there is no obvious link between many of the clusters, raising the possibility of undetected, local transmission of the virus.
“We need to act quickly and decisively, but there is still a lot to be learned,” says Anne Rimoin, an epidemiologist at the University of California, Los Angeles, who has studied monkeypox in the Democratic Republic of the Congo for more than a decade.
Nature outlines some of the key questions about the recent outbreaks that researchers are racing to answer.
How did the current outbreaks start?
Since the latest outbreaks began, researchers have sequenced viral genomes collected from people with monkeypox in countries including Belgium, France, Germany, Portugal and the United States. The most important insight they have gained so far is that each of the sequences closely resembles that of a monkeypox strain found in western Africa. The strain is less-lethal — it has a death rate below 1% in poor, rural populations — than another that has been detected in central Africa and has a death rate up to 10%.
Monkeypox goes global: why scientists are on alert
Clues have also emerged as to how the outbreak might have begun. Although researchers need more data to confirm their suspicions, the sequences they have evaluated so far are nearly identical, suggesting that the recent outbreaks outside of Africa might all be linked back to a single case with a thorough epidemiological investigation.
The current sequences are most similar to those from a smattering of monkeypox cases that arose outside of Africa in 2018 and 2019 and that were linked to travel in western Africa. The simplest explanation is that the person who had the first non-African case this year — who has still not been identified — became infected through contact with an animal or human carrying the virus while visiting a similar part of Africa, says Bernie Moss, a virologist at the National Institute of Allergy and Infectious Disease in Bethesda, Maryland.
But other explanations cannot be ruled out, says Gustavo Palacios, a virologist at the Icahn School of Medicine at Mount Sinai in New York City. It’s possible, that the virus was already circulating, undetected, outside of Africa in humans or animals, introduced during earlier outbreaks. This hypothesis, however, is less likely because the monkeypox virus usually causes visible lesions on people’s bodies — which would probably be brought to the attention of a physician.
Can a genetic change in the virus explain the latest outbreaks?
Understanding whether there is a genetic basis for the virus’s unprecedented spread outside Africa will be incredibly difficult, says Elliot Lefkowitz, a computational virologist at the University of Alabama at Birmingham who has studied poxvirus evolution. Researchers are still struggling to characterize precisely which genes are responsible for the higher virulence and transmissibility of the central African strain, compared with the west African one, more than 17 years after they identified a difference between the two.
Smallpox and other viruses plagued humans much earlier than suspected
One reason for this is that poxvirus genomes contain many mysteries, Lefkowitz says. The monkeypox genome is enormous relative to that of many other viruses — it is more than six times as large as the genome for the SARS-CoV-2 coronavirus. That means they’re at least “six times harder to analyse”, says Rachel Roper, a virologist at East Carolina University in Greenville, North Carolina.
Palacios says another reason is that few resources have been dedicated to genomic surveillance efforts in Africa, where monkeypox has been a public-health concern for many years. So virologists are flying somewhat blind right now, because they have few sequences to which they can compare the new monkeypox sequences, he says. Funding agencies have not heeded scientists who have been warning for more than a decade that further monkeypox outbreaks could occur, he adds.
Ifedayo Adetifa, the head of the Nigeria Centre for Disease Control says that African virologists he’s spoken with have expressed irritation that they’ve struggled to garner funding and publish studies about monkeypox for years — but now that it’s spread outside the continent, public-health authorities worldwide suddenly seem more interested.
To understand how the virus evolves, it would also be useful to sequence the virus in animals, Palacios says. The virus is known to infect animals — mainly rodents such as squirrels and rats — but scientists have yet to discover its natural animal reservoir in the impacted areas of Africa.
Can the outbreaks be contained?
Since the current outbreaks began, some nations have been procuring smallpox vaccines, which are thought to be highly effective against monkeypox, because the viruses are related. Unlike the vaccines against COVID-19, which take up to two weeks to offer full protection, smallpox vaccines are thought to protect against monkeypox infection if administered within four days of exposure because of the virus’s long incubation period, according to the US Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia.
The race to unravel the biggest coronavirus outbreak in the United States
If deployed, the vaccines would probably be applied using a ‘ring vaccination’ strategy, which would inoculate close contacts of infected people. Andrea McCollum, an epidemiologist who heads the poxvirus team at the CDC, says the agency is not yet deploying a ring vaccination strategy. But in the meantime, CNN reports that the United States plans to offer smallpox vaccines for some healthcare workers treating infected people. It might also be worth considering vaccinating groups at higher risk of infection in addition to close contacts of infected people, Rimoin says.
Even if public-health officials halt transmission of monkeypox in humans during the current outbreaks, virologists are also concerned that the virus could spill back into animals. Having new reservoirs of virus in animals would increase the probability of it being transmitted to people again and again, including in countries that don’t host any known animal reservoirs of the virus. On 23 May, the European Centre for Disease Prevention and Control highlighted this possibility, but deemed the probability as “very low”. Still, European health officials strongly recommended that pet rodents such as hamsters and guinea pigs belonging to people with confirmed cases of monkeypox be isolated and monitored in government facilities or euthanized to avoid the possibility of spillover.
Although the risk is low, Moss says the main concern is that scientists wouldn’t know if such a spillover event occurred until it was too late, because infected animals don’t typically show the same visible symptoms as humans.
Is the virus spreading differently now compared with previous outbreaks?
Monkeypox virus is known to spread through close contact with the lesions, bodily fluids and respiratory droplets of infected people or animals. But health officials have been examining sexual activity at two raves in Spain and Belgium as drivers of monkeypox transmission, according to the Associated Press, raising speculation that the virus has evolved to become more adept at sexual transmission.
Prairie-dog model offers hope of tackling monkeypox virus
Cases linked to sexual activity don’t mean that the virus is more contagious or is transmitted sexually, however — just that the virus spreads readily through close contact, Rimoin says. Unlike SARS-CoV-2, which isn’t thought to linger on surfaces much, poxviruses can survive for a long time outside the body, making surfaces such as bedsheets and doorknobs a potential vector of transmission, Roper says.
Although health officials have noted that many cases have been among men who have sex with men (MSM), Rimoin emphasizes that the most likely explanation for the virus’s spread among MSM groups is that the virus was coincidentally introduced into the community, and it has continued spreading there.
All of the new attention on monkeypox has laid bare just how much scientists have yet to understand about the virus, McCollum says. “When this has all settled down, I think we’ll have to think long and hard about where the research priorities are,” she says.
doi: https://doi.org/10.1038/d41586-022-01493-6