流行地區以外的猴痘爆發：科學和社會之優先事項
資料來源：www.thelancet.com/infection Vol 22 July 2022 / 財團法人台灣紅絲帶基金會編譯
隨著世界從 COVID-19 大流行的衝擊中恢復過來，並反思從全球公共衛生系統未能遏制全球 SARS-CoV-2 爆發中吸取的教訓，新傳染病由全球人口流動造成的疾病威脅仍然無處不在，而一再呼籲採取更積極主動的行動卻無人理會。自 2022 年 5 月 7 日以來，在歐洲、美洲和澳大利亞爆發的史無前例和出人意料的人類猴痘病例和群聚恰當地證明了這一點，這再次讓全球公共當局感到意外。
在持續爆發的疫情中，英國衛生安全局於 5 月 7 日報告的首例猴痘病例與奈及利亞有旅行聯繫。5 月 14 日，英國又發現了兩例病例，他們都住在同一個家庭，但沒有旅行過非洲的歷史並和5 月 7 日報告的該病例沒有接觸。世衛組織三個區署的 12 個成員國不斷向世衛組織報告了額外的猴痘病例。截至 2022 年 5 月 21 日，英國、美國、加拿大、法國、德國、比利時、西班牙、葡萄牙、意大利、瑞典和澳大利亞向世衛組織報告了 92 例實驗室確診病例和 28 例疑似猴痘病例。預計會有更多病例。這些病例之間的流行病學聯繫仍有待確定。幸運的是，迄今為止還沒有死亡報告。然而，這些爆發有幾個不尋常、非典型和令人困惑的方面，是重大的科學、公共衛生和社會關注的問題。
首先，僅在英國發現首例病例後 2 週內在英國及其他非屬非洲疫區等地方所發現的猴痘病例遠遠超過了自1970年它成為人類病原體以來的數量。這種顯著增長的科學、環境和社會原因仍然是一個謎，需要通過統一、全球普遍的健康一體( One Health )（人類、環境和動物）的方法來緊急描述。
其次，迄今為止正在進行的流行病學調查顯示，這些病例與非洲猴痘流行地區沒有實質性的旅行聯繫，這是非常不尋常和令人擔憂的。這可能顯示猴痘病毒可能已經在歐洲傳播有一段時間，經由與被感染的無症狀或有症狀的人密切身體接觸而發生人與人之間的傳播，且並未被發現。
第三，這些事件是否是由於猴痘病毒傳播特性的變化或毒力增加仍然未知。與RNA病毒相比，猴痘病毒是一種大型DNA病毒，在檢測和修復突變方面能力比RNA病毒更穩定、更高效。因此，病毒不太可能已進化為增加人類的傳播。初步基因組序列的數據顯示此波疫情與西非流行的猴痘進化枝有關，當與中非的進化枝相比，西非進化枝所引起的疾病較輕，死亡率更低。
第四，大多數猴痘病例是在男男性行為者中發現，有一些病例則係發生在歐洲曾前往最近的節日的男男性行為者和雙性戀男性當中。猴痘是否透過性傳播需要在所有地理環境中進一步仔細研究。在大規模集會活動中，任何密切接觸的群體都可能發生病毒群聚感染。公眾和社交媒體對在這些情況下傳播猴痘的強烈報導，透過使用語言、對話和內容，引發了各種形式的炒作，間接或直接負面地產生加劇污名的恐同和種族主義之刻板印象。這是偏見、不公平和污名化且係不能被接受的。由愛滋病毒和愛滋病之應對工作上的經驗顯示，污名化和指責會破壞對疫情的應對，亦強調了應普遍地建立基於人權、非污名化的疫情應對措施以及以社區為主導的防疫計畫的需要。
第五，猴痘爆發暴露了在了解病毒傳播動力學和不斷演變的疾病流行病學特徵方面上存在重大差距，早就應該採取更協調性的流行病學防範方法卻長期延遲。目前大多數猴痘病例爆發於 20-50 歲的男性。天花疫苗業於 1980 年代在世界範圍內停止接種，在此之前非洲的猴痘病例相對較少。這個年齡層的人數增加可能反映了由於未接種天花疫苗，而喪失了對猴痘的交叉保護免疫力。用於治療重症猴痘病例的抗病毒藥物 tecovirimat 和第三代天花疫苗 Imvanex（該疫苗由位於丹麥海勒魯普的Bavarian Nordic公司所生產），用於所有密切和與高風險病例接觸者的預防投藥，並涵蓋如何使用它們的指引，均需要以可承受的成本下緊急普遍地提供。
第六，猴痘在歐洲的出現和迅速傳播引發了激烈的科學、政治和媒體活動。快速發展的步伐、不斷提高的病例檢測率以及來自全球公共衛生當局的即時不斷演變和累積的數據，加劇了公眾的焦慮。針對猴痘相關風險以及與受影響的社區鼓勵其在預防、檢測和照護方面上的參與之雙向溝通，對於防止猴痘的進一步傳播變得很重要。
第七，在自然界中，猴痘病毒通過囓齒動物或受感染的人類傳播給人類。每年在西非和中非發現數百例人類猴痘病例；在非洲以外看到的少數病例都與前往非洲或與進口的受感染囓齒動物接觸有關。囓齒動物在有非洲旅行史的英國猴痘病例中的作用，反映了當前在奈及利亞發生人類猴痘感染的流行浪潮可能係由於在 COVID-19 封鎖期間接觸囓齒動物的風險增加。這些人傳人的次波流行病學循環可能會影響國際旅行者。針對囓齒動物動力學和流行區域內外的猴痘病例，需要與病毒基因組一致的進一步研究，以發現當前猴痘流行的可能驅動因素。
當前猴痘爆發的優先事項應該是阻止進一步傳播和保護第一線醫護人員以及在全球具最大風險的人。過去 3 周非洲以外猴痘病例出現前所未有的多倍增長，這也再次凸顯了從源頭去發展有效能力，對威脅全球衛生安全能夠有效地做好全球公共衛生準備和人畜共通傳染病之監測上至關重要。需要為此提供政治支持，以增加信心，而不是恐懼和污名化。
AZ、NH、DA、FN 和 RK 是泛非洲傳染病流行病快速研究、響應、救濟和準備網絡的成員，該網絡由歐洲和發展中國家臨床試驗夥伴關係資助，並得到 Horizon 2020（歐盟研究和創新框架計畫）的支持。 AZ 擁有英國國家衛生研究院高級研究員獎，並且是馬哈蒂爾科學獎和帕斯科爾·莫昆比獎的獲得者。所有作者都對流行病感染感興趣。
*Alimuddin Zumla、Sofia R Valdoleiros、Najmul Haider、Danny Asogun、Francine Ntoumi、Eskild Petersen、Richard Kock
a.zumla@ucl.ac.uk。
英國倫敦大學學院臨床微生物學中心感染與免疫學系感染系，倫敦（AZ）； NIHR 生物醫學研究中心，倫敦大學學院醫院 NHS 基金會信託基金，英國倫敦 NW1 OPE（AZ）；葡萄牙波爾圖聖若昂中央醫院大學傳染病科（SRV）；英國皇家獸醫學院，北邁姆斯，哈特菲爾德，赫特福德郡，英國（NH，RK）； 奈及利亞Irrua 專科教學醫院，Irrua，奈及利亞 (DA)；剛果醫學研究基金會，剛果共和國布拉柴維爾（FN）；丹麥奧胡斯市奧胡斯大學臨床醫學研究所 (EP)
Monkeypox outbreaks outside endemic regions: scientific and social priorities
As the world recovers from the shock of the COVID-19 pandemic and reflects on lessons learnt from failure of global public health systems to contain the global outbreak of SARS-CoV-2, new infectious disease threats, caused by movement of people globally, remain omnipresent, and repeated calls for more proactive action go unheeded. This is aptly shown by the unprecedented and unexpected outbreaks of human monkeypox cases and clusters since May 7, 2022, across Europe, the Americas, and Australia, which yet again, have taken global public authorities by surprise.
In the ongoing outbreak, the first monkeypox case reported by the UK Health Security Agency on May 7, had travel links to Nigeria. On May 14, two more cases were identified in the UK, both lived in the same household but had no travel history to Africa and no contact with the case reported on May 7. Additional monkeypox cases have continuously been reported to WHO from 12 member states across three WHO regions. As of May 21, 2022, there have been 92 laboratoryconfirmed cases and 28 suspected monkeypox cases reported to WHO from the UK, the USA, Canada, France, Germany, Belgium, Spain, Portugal, Italy, Sweden, and Australia. Detection of more cases is anticipated. The epidemiological links between these cases remain to be defined. Fortunately, there have been no deaths reported to date. However, there are several unusual, atypical, and perplexing aspects of these outbreaks that are of major scientific, public health, and social concern. First, the number of monkeypox cases detected in this outbreak 2 weeks since first case detection in the UK alone has, by far, surpassed the total number of cases detected in the UK and outside monkeypox-endemic Africa zones since the first discovery of monkeypox in 1970 as a human pathogen. The scientific, environmental, and social reasons for this phenomenal increase remain an enigma and require urgent delineation through a unified, universal One Health (human, environmental, and animal) approach.
Second, it is very unusual and worrying that ongoing epidemiological investigations to date have revealed no substantial travel links of the cases to monkeypoxendemic areas in Africa. This could indicate that the monkeypox virus might already have been spreading undetected in Europe for a while, with human-to- human transmission occurring due to close physical contact with infected asymptomatic or symptomatic people.
Third, whether these events are due to change in monkeypox virus transmission properties or increased virulence remains unknown. Compared with RNA viruses, the monkeypox virus is a large DNA virus, which makes itself more stable and efficient than RNA viruses at detecting and repairing mutations. Thus, it is unlikely that the virus has evolved to increase human transmission. Preliminary genomic sequence data indicate a relationship with monkeypox clades circulating in west Africa, which cause milder disease and have a lower death rate than clades in central Africa.
Fourth, most monkeypox cases have been detected in men who have sex with men and some cases in Europe occurred in men who have sex with men and bisexual men who travelled to recent festivals. Whether monkeypox is sexually transmitted requires further careful study in all geographical settings. Clusters of viral infections can occur in any group in close contact at mass gathering events. The intense public and social media coverage regarding the spread of monkeypox in these contexts has generated hype in its various forms through use of language, conversation, and content, indirectly or directly negatively generating homophobic and racist stereotypes that exacerbate stigma. This is prejudicial, unfair, stigmatising, and unacceptable. Lessons from the HIV and AIDS response showed that stigma and blame undermines outbreak response, highlighting the universal need for building humanrights-based, non-stigmatising outbreak responses and community-led epidemic prevention programmes.
Fifth, the monkeypox outbreaks expose major gaps in understanding the dynamics of viral transmission and continuously evolving epidemiological characteristics of the disease, and a more coordinated approach to epidemic preparedness is long overdue. Most monkeypox cases in the current outbreak are in men aged 20–50 years. Smallpox vaccination was discontinued worldwide in the 1980s and cases of monkeypox in Africa were comparatively small before this. This increase in numbers in this age group might reflect the loss of cross-protective immunity to monkeypox from not receiving the smallpox vaccination. The antiviral tecovirimat for treatment of seriously ill monkeypox cases, and the third-generation smallpox vaccine Imvanex (Bavarian Nordic, Hellerup, Denmark) for use as prophylaxis in all close and high-risk case contacts, together with specific guidelines for their use, need to be made available urgently universally at affordable cost.
Sixth, the appearance and rapid spread of monkeypox in Europe has generated intense scientific, political, and media activity. The rapid pace of developments, increasing case-detection rates, and accumulating realtime evolving data from global public health authorities have fuelled public anxieties. Two-way communication on monkeypox-related risks and engagement of affected communities on prevention, detection, and care becomes important for preventing further spread of monkeypox.
Seventh, in nature, the monkeypox virus transmits to humans from either rodents or from infected humans. Hundreds of cases of human monkeypox are detected in west and central Africa annually. The few cases seen outside Africa have all been associated with travel to Africa or contact with imported infected rodents.2,5,9 The role of rodents in the UK monkeypox cases with history of travel to Africa4,5,9 might reflect the current wave of human monkeypox infections occurring in Nigeria consequential to increased exposures to rodents during the COVID-19 lockdown periods. These secondary epidemiological cycles with human-to-human spread might be affecting international travellers. Further study on rodent dynamics and monkeypox cases inside and outside endemic regions aligned to viral genomics is required to detect possible drivers for the current monkeypox epidemic.
Priority for the current monkeypox outbreak should be on stopping further spread and protecting frontline health-care workers, and those most at risk globally. The unprecedented manifold increase in monkeypox cases seen in the past 3 weeks outside Africa yet again highlights that developing effective capacity at source is crucial for effective global public health preparedness and surveillance for zoonotic threats to global health security.1,2 Rapid garnering of financial and political support for this is required to fuel reassurance, rather than fear and stigmatisation.
AZ, NH, DA, FN, and RK are members of the Pan-African Network for Rapid Research, Response, Relief and Preparedness for Infectious Diseases Epidemics funded by the European and Developing Countries Clinical Trials Partnership, which is supported by Horizon 2020, the EU’s Framework Programme for Research and Innovation. AZ holds a UK National Institute of Health Research Senior Investigator Award and is a Mahathir Science Prize and Pascoal Mocumbi Prize laureate. All authors have an interest in epidemic infections.
*Alimuddin Zumla, Sofia R Valdoleiros, Najmul Haider, Danny Asogun, Francine Ntoumi, Eskild Petersen, Richard Kock
a.zumla@ucl.ac.uk
Department of Infection, Division of Infection and Immunity, Centre for Clinical Microbiology, University College London, London, UK (AZ); NIHR Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London NW1 OPE, UK (AZ); Infectious Diseases Department, Centro Hospitalar Universitário de São João, Porto, Portugal (SRV); The Royal Veterinary College, North Mymms, Hatfield, Hertfordshire, UK (NH, RK); Irrua Specialized Teaching Hospital, Irrua, Nigeria (DA); Congolese Foundation for Medical Research, Brazzaville, Republic of the Congo (FN); Institute for Clinical Medicine, Aarhus University, Aarhus, Denmark (EP)
www.thelancet.com/infection Vol 22 July 2022