猴痘疫情正在消退——但究竟是為什麼呢？
有模型顯示關鍵是一小部分人免疫力的提升而不是接種疫苗
資料來源：Kai Kupferschmidt / 2022 年 10 月 28 日 / 第 378 卷第 6618 343 期 / 科學 / 財團法人台灣紅絲帶基金會編譯
路過的波浪
世界衛生組織兩個受災最嚴重的地區——歐洲和美洲——這兩個國家的猴痘病例都在急劇下降。
今年夏天，當歐洲的猴痘病例開始下降時，研究人員的第一個問題是：這是真的嗎？ 一些人擔心，由於對病毒的恐懼消退，加上對患者的嚴格隔離要求，人們可能不會接受檢測。世界衛生組織 (WHO) 歐洲區域辦事處的猴痘事件經理 Catherine Smallwood 說：「他們可能不願意被確診並被告知根本不要外出」。
但現在下降是顯而易見的。世衛組織歐洲分部在 7 月的高峰期間每週報告 2,000 多例病例，現在每週統計約 100 例病例。 在爆發的另一個主要震中美洲，數字下降了一半以上（見圖）。「我們看到了真正的下降」，斯莫爾伍德說。
倫敦帝國理工學院傳染病模型師埃里克·沃爾茲 (Erik Volz) 說，疫苗接種、受影響最嚴重的群體（男男性行為者，MSM)）的行為改變以及自然感染後的免疫力都在這種下降中發揮了作用，但每個因素的貢獻影響有多大尚不清楚。「這是我們在內部爭論了很多的事情」。
答案很重要，因為它決定了病毒捲土重來的可能性。了解到目前為止導致病例減少的原因也將有助於制定策略，以消除非洲流行國家以外的病毒，這是世衛組織歐洲已經在推動的目標。
根據華威大學傳染病建模師塞繆爾·布蘭德本月在預印本上發布的模型，至少在英國，疫苗接種運動發揮了次要作用。布蘭德指出，猴痘的再生數——由感染者引發的新感染的平均數量——到 6 月中旬開始下降，儘管運動是在 7 月才開始的。其他幾個歐洲國家也看到了同樣的模式。
這就留下了行為改變和自然感染後的免疫力。美國疾病控制和預防中心 8 月份對 MSM 進行的一項調查發現，大約一半的人減少了他們的性接觸次數。 隨著對該病認識的提高，人們也更有可能及早尋求診斷和治療，並在感染期間避免性行為。 英國衛生安全局提供的數據顯示梅毒和其他性傳播感染也有所下降——這將支持行為改變的理由——儘管該信號「具有啟發性但不是決定性的」，Volz 說。
然而，性生活最活躍的男性透過感染獲得的免疫力可能是最大的因素。猴痘主要影響 MSM 及其性網絡，因為這些網絡的某些部分緊密相連，有些人有大量的性接觸。荷蘭國家公共衛生與環境研究所首席流行病建模師 Jacco Wallinga 說，該群體免疫力的提高可能會限制病毒的傳播能力。 「因為性接觸次數多的人也是感染風險最高的人，自然感染導致的易感人群消耗非常快」，他說。他的模型顯示，在英國估計每月有 120 個或更多性伴侶的 1,000 人中，「可能有一半在高峰期被感染」。不過，Brand 表示，他的模型顯示，這一小部分 MSM 人群中的感染並不能單獨解釋觀察到的下降。 他說，「我認為這不太合理」，因為行為改變也發揮了作用。
對於 Smallwood 來說，這引起了一個擔憂：對病例數直線下降感到放心的 MSM 可能會恢復到他們過去的行為。她說，這就是為什麼現在為高危人群接種疫苗可能比流行病高峰期更為重要；事實上，他的英國模型顯示，儘管未來幾個月病例可能會略有上升，但疫苗接種應該可以防止真正的死灰復燃。「我認為目前沒有自滿的餘地」，他說。
從非流行國家整體徹底消除這種病毒可能很困難。「最後一點總是最難的」，斯莫爾伍德說。其中的原因包括恥辱和歧視。「在許多國家/地區，[受感染的人]不會出現純粹是因為擔心他們會受到怎樣的對待」，她說。 此外，埃默里大學的病毒學家 Boghuma Titanji 說，很明顯，有些人是無症狀感染者，他們可能會在不知不覺中傳播病毒。
Smallwood 說，即使歐洲或美國設法消滅了這種病毒，在該病毒仍在人類中傳播的國家，從性網絡重新引入仍將是一種威脅。病毒的最終來源將保持不變：病毒在非洲傳播的動物物種，偶爾會傳染給人類，就像幾十年來一樣。Smallwood 說：「這不是只需要解決疫情爆發之問題後，那風險就可以自然消除了」。
Monkeypox outbreak is ebbing—but why exactly?
Models suggest rising immunity in a small group of people, not vaccination, is key
By Kai Kupferschmidt / 28 OCTOBER 2022 • VOL 378 ISSUE 6618 343 / Science
When monkeypox cases in Europe began to decline this summer, researchers’ first question was: Is it real? Some worried that people might not be getting tested because of receding fears of the virus, coupled with strict isolation requirements for patients. “They might be reluctant to be confirmed and be told not to go out at all,” says Catherine Smallwood, monkeypox incident manager at the World Health Organization’s (WHO’s) Regional Office for Europe.
But the decline is now unmistakable. WHO Europe, which reported more than 2000 cases per week during the peak in July, is now counting about 100 cases weekly. In the Americas, the other major epicenter of the outbreak, numbers have dropped by more than half (see graphic, right). “We’re seeing a true decline,” Smallwood says.
Vaccines, behavior change among the most affected group—men who have sex with men (MSM)—and immunity after natural infection are all playing a role in that decline, says Erik Volz, an infectious disease modeler at Imperial College London, but how much each factor has contributed is unclear. “This is something we’ve debated a lot internally.”
The answer is important because it determines the likelihood of a resurgence of the virus. Knowing what has driven down cases so far will also help shape strategies to eliminate the virus outside endemic countries in Africa, a goal WHO Europe is already pushing for.
In the United Kingdom, at least, vaccination campaigns have played a minor role, according to a model published as a preprint this month by Samuel Brand, an infectious disease modeler at the University of Warwick. Monkeypox’s reproductive number—the average number of new infections triggered by an infected person— began to drop by mid-June, even though campaigns only started in July, Brand notes. Several other European countries saw the same pattern.
That leaves behavior change and immunity from natural infections. A survey conducted by the U.S. Centers for Disease Control and Prevention among MSM in August found about half had reduced their number of sexual contacts. As awareness of the disease increased, people also became more likely to seek diagnosis and treatment early and to avoid sex while they were infectious. The UK Health Security Agency has presented data suggesting syphilis and other sexually transmitted infections declined as well—which would bolster the case for behavior change— although that signal is “suggestive but not conclusive,” Volz says.
Immunity acquired through infections in the most sexually active men may be the biggest factor, however. Monkeypox has been affecting mostly MSM and their sexual networks because parts of those networks are densely connected, with some people having a large number of sexual contacts. Rising immunity in that group could limit the virus’ ability to spread, says Jacco Wallinga, chief epidemic modeler at the Dutch National Institute for Public Health and the Environment. “Because the persons with a very high number of sexual contacts are also those at the highest risk of infection, the depletion of susceptibles due to natural infection is very rapid,” he says. Brand agrees. His model suggests that among the estimated 1000 people in the United Kingdom who have 120 sexual partners per month or more, “maybe half got infected by the time of the peak.” Still, Brand says his model suggests infections among this small part of the MSM population cannot explain the observed decline on their own. “I don’t think it is as plausible” as behavior change playing a role as well, he says.
For Smallwood, that raises a concern: that MSM who feel reassured by the plummeting case numbers may revert to their past behavior. That’s why vaccination of at-risk groups may now be more important than it was at the peak of the epidemic, she says. Brand agrees; in fact, his U.K. model suggests that although a slight uptick in cases in the coming months is likely, vaccinations should prevent a real resurgence. “I don’t think there’s room for complacency at this point,” he says.
Eliminating the virus altogether from nonendemic countries may be difficult. “That last bit is always the hardest,” Smallwood says. Among the reasons are stigma and discrimination. “In many countries, [infected people] will not be presenting purely because they’re concerned about how they may be treated,” she says. Besides, it has become clear that some people have asymptomatic infections and could pass on the virus unknowingly, says Boghuma Titanji, a virologist at Emory University.
Even if, say, Europe or the United States managed to eliminate the virus, reintroductions from sexual networks in countries where the virus is still circulating in humans would remain a threat, Smallwood says. And the ultimate source of the virus will remain untouched: the animal species in Africa where the virus circulates, occasionally spilling over to humans, as it has for decades. “This is not an outbreak that just needs to be fixed, and then the risk is gone,” Smallwood says.