為什麼猴痘主要攻擊男男性行為者
曾經緩慢傳播的病毒可能在緊密連接的性網絡中找到了新的利基
資料來源：Kai Kupferschmidt / 2022 年 6 月 24 日 VOL 376 ISSUE 6600 / SCIENCE / 財團法人台灣紅絲帶基金編譯
猴痘病毒顆粒的彩色透射電子顯微照片。在過去的幾個月裡，該病毒已使 30 多個國家的 3000 多人患病。
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自從今年春天猴痘開始感染全球數千人以來，兩個大問題迫在眉睫：為什麼一種從未成功傳播到非洲以外的少數病例的病毒突然導致如此大規模的全球爆發？為什麼絕大多數男男性行為者（MSM）受影響？對性傳播感染 (STI) 的長期研究和對當前疫情的早期研究顯示，答案可能是相關的：該病毒可能已經進入男男性行為者社區內高度相互關聯的性網絡中，在那裡它可以透過多種方式傳播它卻不能在一般人群中。
上週，倫敦衛生與熱帶醫學院 (LSHTM) 的研究人員以預印本形式發布的一項流行病學建模研究支持了這一想法。這顯示，如果不加以遏制，疫情將繼續迅速增長。該模型還對如何保護高危人群和限制傳播產生了影響，同時顯示更廣泛人群的風險仍然很低。
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耶魯大學公共衛生學院 Gregg Gonsalves：「我認為我們必須更多地談論性」。
但是仍然存在許多不確定性，而且由於存在對男男性行為者進行污名化的風險，而且因為坦率地就性行為進行溝通很困難，所以溝通充滿了挑戰。「我認為我們必須更多地談論性」，耶魯大學公共衛生學院流行病學家和前愛滋病毒活動家格雷格·貢薩爾維斯(Gregg Gonsalves)說。「每個人都對污名非常清楚，並且一遍又一遍地說。關鍵是你仍然必須解決我們社區的感染風險」。
自 5 月初以來，已在 30 多個通常不出現這種病毒的國家報告了 3000 多例猴痘病例。 （疫情在西非和中非的許多國家更為常見，那裡的病毒有動物宿主。今年已確認有 60 多例病例和 1 例死亡。）
當前爆發的絕大多數病例發生在男男性行為者中。例如，英國衛生安全局的研究人員要求患者填寫問卷。該團隊在 6 月 10 日發布的技術簡報中寫道，在 152 人中，有 151 人說他們是男男性行為者；剩下的病人拒絕回答。其他國家也看到了類似的模式。
當然，這可能是一個扭曲的畫面。「與異性戀男性相比，男男性行為者與醫生的關係更好」，倫敦帝國理工學院傳染病建模師 Lilith Whittles 說，這可能意味著他們更有可能報告猴痘症狀並接受病毒檢測。「我不知道我們是否必須在異性戀社交網絡中進行足夠多的研究，才能得出這不是一個更廣泛的問題之結論」，在一家性健康診所工作的埃默里大學病毒學家 Boghuma Titanji 說。
但大多數研究人員表示，這種「確定性偏差」不太可能解釋這種驚人的模式。雖然一些猴痘患者有可能被漏診或誤診的輕度感染，但其他人有非常典型的皮疹和痛苦的疼痛，需要住院治療疼痛。如果男男性行為者社區以外的許多人患有猴痘，那麼現在統計數據中會顯示更多。
多倫多大學傳染病流行病學家 Ashleigh Tuite 表示，她「理解關注男男性行為者的猶豫」，因為污名化的風險可能會加劇歧視並導致受影響的人延遲尋求治療。「但根據我們掌握的數據，以及已經完成的接觸者追踪，很明顯，目前這是一場以男男性行為者為重點的疫情」，她說。美國疾病控制和預防中心的愛滋病毒預防專家 Demetre Daskalakis 證實：「任何人都可能感染猴痘，但我們看到的主要是男男性行為者中的疾病活動」。
性接觸顯然在傳播中起作用。在英國衛生安全局數據集中的 152 人中，有 82 人被邀請進行額外的採訪，重點關注他們的性健康。在參與的 45 人中，44% 的人報告前 3 個月有超過 10 名性伴侶，44% 的人報告在潛伏期發生集體性行為。病毒究竟是如何傳播的還不太清楚。研究人員在一些患者的精液中發現了病毒 DNA，甚至是傳染性病毒，但他們不確定這對傳播是否重要；皮膚接觸可能就足夠了。（其他性傳播感染，包括皰疹和疥瘡，也主要通過這種方式傳播。）
對於那些研究病原體如何透過社會和性網絡傳播的人來說，這種模式並不令人意外。倫敦衛生與熱帶醫學院的流行病學家亞當·庫查爾斯基 (Adam Kucharski) 說，在 1970 年代和 80 年代，試圖了解淋病等性傳播疾病傳播的研究人員遇到了困難：調查數據顯示，人們的性伴侶平均數量太少，無法維持傳播。但平均值遮蔽了實況，儘管許多人的性伴侶很少，但有些人的數量很多。這有助於推動傳播，因為如果被感染，他們更有可能感染他人。
Wittles 強調，男男性行為者之間的性網絡在本質上與其他群體的性網絡沒有什麼不同，但核心群體的緊密聯繫比其他社區中來得多。他們更頻繁地更換伴侶，並且更有可能同時擁有多個伴侶。「這些事情發生在所有的性網絡中，但只是程度的問題」，惠特爾說。而且在一個緊密連接的網絡中，病毒不太可能陷入死胡同。
哈佛大學 FXB（註1）健康與人權中心的社交網絡流行病學家 Keletso Makofane 說：「這種流行病完全有可能在一小部分人中肆虐，只是因為該部分人在網絡中的連接方式與其他人不同」。 Makofane 希望 8 月在紐約市開展一項研究，以更好地了解這種疾病的傳播。「我們的想法是了解有多少人報告了與猴痘一致的症狀以及他們之間的聯結」，他說。
倫敦衛生與熱帶醫學院的研究於 6 月 13 日發佈在 medRxiv（註2）上，該研究使用英國有關性伴侶模式的數據來模擬猴痘在男男性行為者和該群體之外的傳播。由於尚不清楚該病毒的傳染性如何，研究人員根據不同的風險水平模擬了情景。他們寫道，如果沒有有效的介入措施或行為改變，全球男男性行為者中出現超過 10,000 例病例的大規模持續爆發「極有可能」。「相比之下，在考慮所有的情況之下，非男男性行為者人群中的持續傳播則不太可能」。
第一作者 Akira Endo 說，由於該模型基於英國數據，因此研究結果可能不適用於其他地方。其他因素可能使疫情變得更糟。猴痘可能發生了變異，使其更容易傳播，而接種天花疫苗（也對猴痘提供一些保護）的人口比例正在下降，因為從 1970 年代開始，全世界都禁止接種天花疫苗。但模型顯示「我們不一定需要 [那些因素] 來解釋觀察到的模式」，Endo 說。
建模者的結論使流行病學家處於微妙的境地，有些人因為害怕給男男性行為者蒙上污名而拒絕與《科學》雜誌交談。遠藤說他理解這一點，並同意這些發現很容易被誤解。「與此同時，我也明白，在另一個方向存在風險——在為時已晚之前，信息無法到達最需要的人手中」。
Whittles 表示同意，稱這些發現是「就其傳播地點而言這是實際的信息；這是道德中立的事情」，她說。 「了解正在發生的事情就是力量，即使這種知識是不完美的並且會改變」，Daskalakis 補充道。
該病毒仍然可以找到其他具有類似特徵但非屬性的網絡。 Daskalakis 回憶起 2000 年代美國爆發的耐甲氧西林金黃色葡萄球菌(methicillin-resistant Staphylococcus aureus)，該病始於男男性行為者社區，但後來在體育館、運動員和監獄中蔓延。 Tuite 說，猴痘也可能開始在性工作者及其客戶中傳播。
病毒在未來幾個月的傳播速度取決於控制措施。歐洲、加拿大和美國的國家衛生當局已經發布了關於如何降低感染風險的指南，約會應用程序已經提醒用戶注意猴痘的風險及其症狀，這可能會改變接觸模式。 Whittles 說，提高衛生保健工作者的意識也可能產生影響：更快的診斷意味著患者將在感染中更快地被隔離，從而減少繼續傳播。「所以有幾種不同的方式可以改變行為，即使不是人們的性生活減少」，她說。隨著感染者產生免疫力，「我們可能會比我們想像的更早看到疫情的放緩」，Endo 說。
許多國家正準備開展免疫運動。 針對有許多性伴侶的人可能是最有效的方法。 在 6 月 21 日發布的指南中，英國衛生安全局宣布將開始向處於最高風險的男男性行為者提供疫苗。 該機構表示：「風險標準將包括近期有多個性伴侶的經歷、參與集體性行為、參加『場所內性行為』之場域或代理標記，例如最近的細菌性性病感染」。
Gonsalves 說，提醒社區並以正確的方式做事很重要。「我們應該說：這與你是誰無關，這是與你在做什麼有關，我們不會去污名化它；但要知道，如果你有符合這種情況，那你將面臨更大的風險」。
註1. François-Xavier Bagnoud Centre for Health and Human Rights 於 1993 年由 Albina du Boisrouvray 創立和捐贈。她的目標是透過推進健康和人權願景來為兒童提供保護。其任務為
使用跨學科方法來促進在全國和世界各地受到種族主義、貧困和污名壓迫的人的公平和尊嚴。並很自豪地能與眾多學者、教育工作者、民選官員、政府機構、非營利組織和國際政策界成員合作，以促進健康和人權，並展示侵權行為對兒童的有害影響。
註2. MedRxiv（發音為「Med-archive」，其中χ是希臘字母χ（kai），而不是拉丁字母X）是醫學、臨床和相關的健康科學領域的開放獲取的預印本資料庫，由冷泉港實驗室、英國醫學期刊(BMJ)出版集團和耶魯大學聯合建立，伺服器的託管與運營由冷泉港實驗室負責。
Why monkeypox is mostly hitting men who have sex with men
The once slow spreading virus may have found a new niche in tightly connected sexual networks
By Kai Kupferschmidt / 24 JUNE 2022 • VOL 376 ISSUE 6600 / SCIENCE
A colorized transmission electron micrograph of monkeypox virus particles. The virus has sickened more than 3000 people in more than 30 countries in the past few months.
Ever since monkeypox started to sicken thousands of people worldwide this spring, two big questions have loomed: Why is a virus that has never managed to spread beyond a few cases outside Africa suddenly causing such a big, global outbreak? And why are the overwhelming majority of those affected men who have sex with men (MSM)? A long history of work on sexually transmitted infections (STIs) and early studies of the current outbreak suggest the answers may be linked: The virus may have made its way into highly interconnected sexual networks within the MSM community, where it can spread in ways that it cannot in the general population.
An epidemiological modeling study posted as a preprint last week by researchers at the London School of Hygiene & Tropical Medicine (LSHTM) supports that idea. It suggests the outbreak will keep growing rapidly if it isn’t curtailed. The model also h as implications for how to protect those most at risk and limit spread, while suggesting the risk for the wider population remains low.
But there are still many uncertainties, and communication is fraught because of the risk of stigmatizing MSM—and because communicating frankly about sexual behavior is hard. “I think we have to talk more about sex,” says Yale School of Public Health epidemiologist and former HIV activist Gregg Gonsalves. “Everybody has been very clear about stigma, and saying it over and over again. The point is that you still have to address the risk of infection in our community.”
Since early May, more than 3000 monkeypox cases have been reported in more than 30 countries where the virus is not normally seen. (Outbreaks are more common in many countries in West and Central Africa, where the virus has animal reservoirs. More than 60 cases and one death have been confirmed there this year.)
The vast majority of cases in the current outbreak have been in MSM. Researchers at the UK Health Security Agency (UKHSA), for example, asked patients to fill out questionnaires. Of 152 who did, 151 said they were MSM, the team wrote in a technical briefing published on 10 June; the remaining patient refused to answer. Other countries have seen similar patterns.
That could be a skewed picture, of course. “MSM have a better relationship with medical practitioners than heterosexual men,” says Lilith Whittles, an infectious disease modeler at Imperial College London, which could mean they are more likely to report monkeypox symptoms and get tested for the virus. “I don’t know that we’re necessarily looking enough in heterosexual social networks to make the conclusion that this is not a broader problem,” says Boghuma Titanji, a virologist at Emory University who works at a sexual health clinic.
But most researchers say such “ascertainment bias” is unlikely to explain the striking pattern. Although some monkeypox patients have mild infections that may be missed or misdiagnosed, others have very characteristic rashes and agonizing pains that require hospitalization for pain treatment. If many people outside the MSM community had monkeypox, more would have shown up in the statistics by now.
Ashleigh Tuite, an infectious disease epidemiologist at the University of Toronto, says she “understands the hesitation” to focus on MSM, given the risk of stigma that could worsen discrimination and cause those who are affected to delay seeking care. “But based on the data that we have, and based on the contact tracing that’s been done, it’s very clear that this is an MSM focused outbreak at this point,” she says. “Anyone can get monkeypox, but we’re seeing disease activity primarily among” MSM, confirms Demetre Daskalakis, an HIV prevention specialist at the U.S. Centers for Disease Control and Prevention.
Sexual encounters clearly play a role in transmission. Of the 152 people in the UKHSA data set, 82 were invited for additional interviews focusing on their sexual health. Among the 45 who participated, 44% reported more than 10 sexual partners in the previous 3 months, and 44% reported group sex during the incubation period. Exactly how the virus is passed on is less clear. Researchers have found viral DNA, and even infectious virus, in the semen of some patients, but they aren’t sure that is important for transmission; skin-to-skin contact may be enough. (Other STIs, including herpes and scabies, also primarily spread this way.)
To those who study how pathogens spread through social and sexual networks, the pattern is not a big surprise. In the 1970s and ’80s, researchers trying to understand the spread of sexually transmitted diseases such as gonorrhea were stumped, says LSHTM epidemiologist Adam Kucharski: Survey data showed people’s average numbers of sexual partners were too low to sustain transmission. But averages obscured that although many people have few sexual partners, some have large numbers. This helps drive transmission because, if infected, they are more likely to infect others.
Sexual networks among MSM are not different in nature from those of other groups, Whittles stresses, but a core group of people are much more densely connected than in other communities. They change partners more frequently and are more likely to have several partners at the same time. “These things occur in all sexual networks, it is just a question of the degree,” Whittles says. And in a densely connected network, the virus is less likely to hit a dead end.
“It’s entirely possible for this epidemic to rage among a subset of people just because that subset is connected in a network differently than everyone else,” says Keletso Makofane, a social network epidemiologist at the FXB Center for Health and Human Rights at Harvard University. Makofane hopes to launch a study in New York City in August to better understand the spread of the disease. “The idea is to get a sense of how many people report symptoms that are consistent with monkeypox and how they are connected,” he says.
The LSHTM study, posted on medRxiv on 13 June, used U.K. data about sexual partnership patterns to model the spread of monkeypox among MSM and outside that group. Because it is not yet clear how contagious the virus is, the researchers modeled scenarios based on different risk levels. Without effective intervention measures or behavioral changes, a large and sustained outbreak with more than 10,000 cases among MSM globally is “highly likely,” they write. “In contrast, sustained transmission in the non-MSM population is unlikely in all scenarios considered.”
Because the model is based on U.K. data, the findings may not apply elsewhere, first author Akira Endo says. And other factors may have made the outbreak worse. Monkeypox may have mutated in ways that allow it to transmit more easily, and the share of the population who have had the smallpox vaccine—which also offers some protection against monkeypox—is declining because smallpox vaccination was abandoned worldwide starting in the 1970s. But the modeling shows “we do not necessarily need [those factors] to explain the observed patterns,” Endo says.
The modelers’ conclusions put epidemiologists in a delicate position, and some declined to talk to Science for fear of stigmatizing MSM. Endo says he understands that and agrees the findings could easily be misunderstood. “Meanwhile I also understand that there’s a risk in the other direction— that the information doesn’t reach those who need it most before it’s too late.”
Whittles agrees, calling the findings “practical information, in terms of where it’s spreading. It is a morally neutral thing,” she says. “Knowledge of what’s happening is power, even though that knowledge is imperfect and will change,” Daskalakis adds.
The virus could still find other nonsexual networks with similar characteristics. Daskalakis recalls a U.S. outbreak of methicillin-resistant Staphylococcus aureus in the 2000s that started in the MSM community but later spread in gyms, among athletes, and in prisons. Monkeypox could also start to spread among sex workers and their clients, Tuite says.
How fast the virus will spread in the months ahead depends on control efforts. National health authorities in Europe, Canada, and the United States have issued guidance about how to reduce the risk of infection, and dating apps have alerted users to the risk of monkeypox and to its symptoms, which may change contact patterns. Increasing awareness among health care workers may have an impact as well, Whittles says: Faster diagnoses mean patients will isolate sooner in their infection, reducing onward transmission. “So there’s a couple of different ways that behavior can change, even if it’s not people having less sex,” she says. And as infected individuals develop immunity, “we may see a slowdown of the outbreak earlier than we might imagine,” Endo says.
Many countries are gearing up to start immunization campaigns. Targeting those with many sexual partners may be the most efficient approach. In guidance published on 21 June, UKHSA announced it would start to offer vaccines to MSM at highest risk. “Risk criteria would include a recent history of multiple partners, participating in group sex, attending ‘sex on premises’ venues or a proxy marker such as recent bacterial STI,” the agency said.
It’s important to alert that community and do it the right way, Gonsalves says. “We should say: It’s not about who you are. It’s about what you’re doing. And we’re not going to stigmatize it. But just know that you’re at greater risk if you fit this profile.”
“I think we have to talk more about sex.” Gregg Gonsalves, Yale School of Public Health