猴痘會成為「21 世紀的梅毒」嗎？

資料來源：Vincent Richeux / 2022 年 8 月 22 日 / Medscape 醫學新聞 / 財團法人台灣紅絲帶基金會編譯

巴黎——法國正在加強疫苗接種活動，以應對猴痘病例的增加。在經歷了緩慢的開局之後，新上任的法國衛生部長弗朗索瓦·布勞恩（François Braun）宣布釋放 42,000 劑疫苗。同時，醫學生將能夠在疫苗接種點提供幫助。然而，一些專家批評所採取的措施過於鬆懈，無法應對世界衛生組織 (WHO) 指定的全球衛生緊急情況。

對於 Raymond-Poincaré 醫院（Paris Public Hospital Trust, AP-HP, Garches region）的傳染病專家 Benjamin Davido, MD, MSc, PhD 來說，這種疾病的風險已經降到最低，但採取的措施還不夠充分，儘管管理該流行病所需的工具已準備就緒。他說，我們必須對這次猴痘流行病所帶來的風險保持警惕，這似乎與中非和西非通常出現的零星爆發不同。 Davido 最近在接受 Medscape 採訪時分享了他的觀點。

Medscape 法語版：您如何看待法國目前正在進行的猴痘疫苗接種活動？

Davido：這還走得遠遠不夠，我對缺乏具體的目標感到驚訝。這種疾病的影響正在被最小化，我們似乎處於冷漠中。看來我們得等到火勢失控才能打電話給消防部門。我們應該從一開始就應更具反應性，並採取更加激進的方法。在法國，與其他受疫情影響的國家一樣，不幸的是，我們仍處於觀察階段，我們向自己保證，這肯定不會成為另一場大流行，因為那真的很倒霉。

然而，我們發現自己處於前所未有的境地：我們早就知道這種疾病，目標人群已經確定，而且我們可以立即獲得疫苗。因此，我們擁有從 COVID-19 大流行中獲得的所有工具和知識，但我們選擇觀望。我們顯然低估了在疫苗接種運動開始停滯後失敗的風險。

Medscape：在您看來，風險究竟是什麼？我們是否應該擔心疫情的進展？

Davido：情況確實令人擔憂。我個人堅信，這種疾病將成為 21 世紀的梅毒。儘管風險很低，但這並非不可能成為新流行病的開始。目前，它的傳播僅限於高危人群，主要是與其他男性發生性關係且有多個伴侶的男性，在法國約有 300,000 人。但是，絕不能將異性戀的風險降到最低；我們絕不能忘記，這種疾病也可以透過與感染者的接觸以及同住的人的呼吸道飛沫傳播。最近有婦女和兒童感染猴痘的病例。如果猴痘開始在社區傳播，而不是透過性傳播感染，這種流行病可能會傳播到其他人群。隨著病例的增加，科學家們也擔心傳染給動物。猴痘可能會像在非洲一樣流行，那裡的囓齒動物是病毒的主要宿主。

Medscape：我們對這種流行病的動態了解多少？可以做些什麼來有效改善這種情況？

Davido：從非洲猴痘國家的經驗，以及2003年美國發生的一連串病例的經驗告訴我們，一旦病例得到控制，疫情是可以控制的。希望猴痘疫苗能夠實現目標，避免進一步的疫情浪潮。

但是我們需要給自己提供這樣做的方法。7 月初將疫苗接種計畫擴大到高危人群是正確的決定。我們已經看到針對密切接觸病例的環形疫苗接種不適用於猴痘。當前的問題是這種疫苗幾乎完全僅限於醫院環境。我們正在犯與 COVID-19 流行開始時 [我們所做的] 相同的錯誤。我們沒有合適的基礎設施來支持這個疫苗接種計畫。我們需要讓醫生、護理人員、藥劑師等參與進來。並減少繁文縟節。在 COVID-19 期間採用數字程序後，我們發現自己必須為每個參加疫苗接種現場的人完成文件的紙質副本。這沒有任何意義！

Medscape：您強調了這次疫苗接種活動缺乏明確的目標。那我們應該瞄準什麼？

Davido：在 COVID-19 疫苗接種活動期間，在給定的時間範圍內有一定數量的人需要接種疫苗。這種方法需要快節奏和預期的結果。是的，這從一開始就是一個雄心勃勃的目標，但這是我們堅持的目標。目前，尚未為猴痘疫苗接種計畫設定任何數字，沒有目標。理想情況下，我們會在新學年開始之前完成疫苗接種活動，以限制新的感染。

目前，只有 10% 的目標人群接種了疫苗。有傳言說夏季不利。但我記得去年，COVID-19 疫苗接種計劃在 8 月中旬得到加強。如果在夏末之前沒有加強猴痘疫苗接種活動，那麼當不同群體在新學年開始度假後混在一起時，我們就有可能鼓勵密切接觸者之間傳播病毒。我認為，首先，我們必須讓全科醫生了解這種疾病，並培訓他們如何診斷，以便盡快隔離患者並接種疫苗。

Medscape：也有人談論增加兩劑之間設定的 28 天期限，甚至完全取消它。這可能會導致更好的疫苗接種嗎？

Davido：英國已選擇單次接種，並建議在接觸個案後進行第二次接種。我不確定這是最好的策略。儘管療效數據仍然有限，但單次接種後效果並不理想。根據法國國家藥品和健康產品安全局 (ANSM) 的初步數據，健康志願者在接種一劑後的D28 天血清轉化率從 10% 上升到 56%，但在 D28 施打第二劑後兩週，則介於 77% 和 89% 之間。

因此，需要第二劑，尤其是免疫記憶似乎在第一次注射後 2 年下降。美國疾病控制和預防中心 (CDC) 建議在兩次給藥之間間隔 35 天。我認為這是一個合理的時間框架。因此，延遲第二劑可以使第一劑的施打更加容易，因為第二劑通常在假期中間發生，因此我們也節省了寶貴的劑量。如果劑量之間的時間更長，我們可能會冒著接種疫苗的人變得鬆懈的風險，並且可能會被誘惑跳過「可選擇」之追加劑或乾脆忘記它。

Medscape：已經接種過天花疫苗的人是否能更好地預防猴痘？

Davido：這種疫苗對猴痘的長期療效並不完美，老實說，我們並不真正了解第一代疫苗在 20 年後提供的保護水準。我們不能忘記，在取消對這種疾病的強制接種之前，有 20% 的猴痘感染者接種了天花疫苗[編者註：天花疫苗被根除後，1979 年取消了接種初始劑的天花疫苗要求]。

希望至少這種疫苗可以預防嚴重疾病；然而，在我的部門，我們經常看到 45 歲以上的嚴重猴痘病例，皮損廣泛，據說他們曾接種了天花疫苗。

Medscape：相比之下，第三代疫苗是否有可能對嚴重疾病提供更好的保護？

Davido：我們仍然沒有足夠的數據或後見之明來評估第三代疫苗對現實世界的影響。這種疫苗比它的前輩有更好的耐受性，但我們目前不知道它是否能預防嚴重的猴痘。我們還需要更多地了解導致當前流行的這個疾病，因為它似乎與中非和西非通常出現的零星爆發不同；所見病變明顯較輕。世衛組織已將這種疫苗對猴痘病毒感染的有效性水平定為 85%，但我們必須保持謹慎：這個數字是基於來自非洲的數據。我們發現自己所處的流行病並不相同。總體而言，我們必須警惕圍繞在這一新流行病上過於樂觀的言論。

本文翻譯自 Medscape 法語版。

Will Monkeypox Be the ‘Syphilis of the 21st Century?’

Vincent Richeux / August 22, 2022 / Medscape Medical News

PARIS — France is boosting its vaccination campaign in response to the increase in cases of monkeypox. After a sluggish start, newly appointed French health minister François Braun has announced the release of 42,000 vaccine doses. At the same time, medical students will be able to lend a helping hand at vaccination sites. However, some experts have criticized the measures taken as being too lax to combat what the World Health Organization (WHO) has designated a global health emergency.

For Benjamin Davido, MD, MSc, PhD, an infectious disease specialist at the Raymond-Poincaré Hospital (Paris Public Hospital Trust, AP-HP, Garches region), the risks of this disease have been minimized and the measures taken are not adequate, despite the ready availability of the tools needed to manage the epidemic. We must remain alert to the risks posed by this monkeypox epidemic, which seems different from the sporadic outbreaks that usually crop up in Central and West Africa, he said. Davido recently shared his opinions in an interview with Medscape.

Medscape French Edition: What do you think about the monkeypox vaccination campaign currently underway in France?

Davido: It doesn’t go far enough, and I am surprised by the lack of a concrete and specific objective. The effects of the disease are being minimized, and we seem to be in limbo. It seems we have to wait until the fire is out of control before we can call the fire department. We should have been more reactive and taken a more drastic approach from the get-go. In France, as in other countries affected by this epidemic, we are still, unfortunately, in a phase of observation, reassuring ourselves that this will surely not become another pandemic, as that would be really bad luck.

Yet we find ourselves in an unprecedented situation: we have known about the disease in question for a long time, the target population has been identified and we have a vaccine immediately available. So, we have all the tools and knowledge acquired from the COVID-19 pandemic at our disposal, yet we are choosing to wait and see. We have clearly underestimated the risks of failing after a stalled start to the vaccination campaign.

Medscape: What exactly are the risks, in your opinion?  Should we already be worried about how the epidemic is progressing?

Davido: The situation is definitely worrying. I personally am convinced that this disease will be the syphilis of the 21st century. Although the risk is low, it is not beyond the bounds of possibility that this could be the start of a new pandemic. For the time being, its spread is limited to at-risk populations, mainly men who have sex with other men and who have multiple partners, which accounts for around 300,000 people in France. However, the risk for heterosexuals must not be minimized; we must not forget that this disease can also be transmitted through contact with an infected person and by respiratory droplets from people living in the same household. There have been recent cases of women and children infected with monkeypox. If monkeypox starts to spread in the community, rather than being a sexually transmitted infection, the epidemic could spread to the rest of the population. With the rise in cases, scientists are also concerned about transmission to animals. Monkeypox could become endemic like it is in Africa, where rodents are the main reservoir of the virus.

Medscape: What do we know about the dynamics of this epidemic?  What can be done to effectively improve the situation?

Davido: Experience gained from African countries affected by monkeypox, as well as from the spate of cases that occurred in the United States in 2003, has shown us that the epidemic can be controlled once the cases have been contained. It is hoped that further waves of the epidemic can be avoided, providing the monkeypox vaccine achieves its objectives.

But we need to give ourselves the means to do so. The expansion of the vaccination program to the most at-risk populations in early July was the right decision. We have seen that ring vaccination targeting close-contact cases does not work with monkeypox. The current problem is that this vaccine is nearly exclusively restricted to hospital settings. We are making the same mistakes as [we did] at the start of the COVID-19 epidemic. We don’t have the right infrastructure in place for this vaccination program. We need to get doctors, paramedics, pharmacists, etc. involved. And cut back on the red tape. After embracing digital procedures during COVID-19, we find ourselves having to complete paper copies of documents for every single person attending a vaccination site. It just doesn’t make sense!

Medscape: You highlighted the lack of a clear objective with this vaccination campaign. What should we be aiming for?

Davido: During the COVID-19 vaccination campaign, there was a set number of people to be vaccinated within a given timeframe. The approach demanded a fast pace and a desired outcome. Yes, it was an ambitious target from the get-go, but it was one that we stuck to. Currently, no figure, no target, has been set for the monkeypox vaccination program. Ideally, we would have completed the vaccination campaign before the start of the new school year to limit new infections.

As it stands now, only 10% of the target population has received the vaccine. There is talk of the summer period not being favorable. Yet I remember that last year, the COVID-19 vaccination program was strengthened in the middle of August. If the monkeypox vaccination campaign is not given a boost by the end of the summer, we run the risk of encouraging transmission of the virus between close contacts when different groups mix after being on holiday at the start of the new school year. I think that, first and foremost, we must make general practitioners aware of the disease and train them in how to diagnose it so that patients can be isolated and vaccinated as quickly as possible.

Medscape: There has also been talk of increasing the set 28-day period between the two doses, or even getting rid of it entirely. Would this perhaps lead to better vaccine uptake?

Davido: The United Kingdom has chosen to give a single dose and recommends a second dose after exposure. I am not sure that this is the best strategy. Although the efficacy data are still limited, the results are not as good after a single dose. According to initial data from the French National Agency for the Safety of Medicines and Health Products (the ANSM), the rate of seroconversion after one dose rises from 10% to 56% on D28 in healthy volunteers, but is between 77% and 89% two weeks after the second dose administered on D28.

So, the second dose is needed, especially as immunological memory seems to drop 2 years after the first injection. The US Centers for Disease Control and Prevention (CDC) propose leaving 35 days between the two doses. I think this is a reasonable timeframe. So, delaying the second dose makes administration of the first dose even easier because the second often fell in the middle of the holiday period and so we also save precious doses. If the time between doses is longer, we risk vaccinated individuals becoming lax and possibly being tempted to skip the “optional” booster or simply forgetting about it.

Medscape: Are people who have already had the smallpox vaccine better protected against monkeypox?

Davido: The efficacy of this vaccine against monkeypox is not perfect on a very long-term basis and, to be honest, we don’t really know the level of protection afforded by first-generation vaccines after 20 years. We must not forget that 20% of people infected with monkeypox were vaccinated against smallpox before mandatory vaccination for this disease was abolished [Editor’s note: The requirement of an initial dose of smallpox vaccine was lifted in 1979, once smallpox had been eradicated].

It is hoped that, as a minimum, this vaccine protects against serious illness. Yet in my department, we regularly see severe cases of monkeypox with widespread lesions in the over 45s, who are said to be vaccinated against smallpox.

Medscape: By comparison, is it likely that a third-generation vaccine would afford better protection against severe illness?

Davido: We still don’t have enough data or hindsight to assess the real-world impact of third-generation vaccines. This vaccine has a better tolerance profile than its predecessors, but we currently don’t know if it protects against severe forms of monkeypox. We also need to learn more about the disease causing the current epidemic, since it seems different from the sporadic outbreaks that usually crop up in Central and West Africa. The lesions seen are notably milder. The WHO has given this vaccine an efficacy level of 85% against infection by the monkeypox virus, but we must remain cautious: this figure is based on data from Africa. The epidemic in which we find ourselves is not the same. Overall, we must be wary of overly optimistic rhetoric around this new epidemic.

This article was translated from the Medscape French edition.