這些猴痘的研究人員警告說這種疾病會蔓延到全球
奈及利亞疾病監測專家和美國流行病學家多年來一直在追踪猴痘。他們的見解能否有助於阻止其傳播並防止未來爆發？
資料來源：Paul Adepoju / 新聞特寫 / 2022 年 11 月 30 日；財團法人台灣紅絲帶基金會編譯
Adesola Yinka-Ogunleye 領導了奈及利亞對 2017 年猴痘疫情的調查。圖片來源：Alecsandra Dragoi for Nature
5 月，當猴痘開始在歐洲及其他地區蔓延時，許多公共衛生專家都大吃一驚。但對於多年來在中非和西非追踪和研究這種病毒性疾病的研究人員來說，唯一的震驚是看到他們的預測有多準確。
位於阿布賈奈及利亞疾病控制中心 (NCDC) 的流行病學家 Adesola Yinka-Ogunleye 說：「我們一直警告說，在有利的情況下，例如導致這次疫情爆發的情況，這種疾病可能對全球健康構成巨大威脅」，他領導了該國對 2017 年猴痘疫情的調查和應對工作。
猴痘的未來會怎樣？
現在，在 100 多個國家/地區有超過 80,000 例確診病例，猴痘清楚地提醒人們如果忽視此類警告會發生什麼。 Yinka-Ogunleye 和流行病學家 Anne Rimoin 等科學家自 2002 年以來一直致力於研究剛果民主共和國 (DRC) 的猴痘疫情，他們在研究病毒如何傳播方面積累了數十年的經驗。他們的實地考察有助於為全球響應提供信息，但還有更多有待發現。 「我們需要回答很多問題」，加州大學洛杉磯分校 (UCLA) 的 Rimoin 說。
《自然》雜誌與兩位研究人員進行了交談，以了解該病毒如何在非洲蔓延，以及可以採取哪些措施來阻止其傳播並防止該疾病未來在全球爆發。
神秘疾病
2017 年 9 月，Yinka-Ogunleye 和她的團隊前往奈及利亞南部的巴耶爾薩，調查人們身上出現難以治療的神秘皮疹的情況。該團隊懷疑皮疹是由猴痘引起的——猴痘是一種與天花有關的病毒，可引起天花。但是這個國家已經有大約 40 年沒有記錄到猴痘病例了；這是當時的醫生和醫學生從未遇到過的情況。根據他們看到的症狀，研究人員首先必須排除天花。
然而，測試無法在奈及利亞進行，需要數週時間。與此同時，他們調查的消息洩露了，公眾開始對潛在的健康危機感到震驚。 NCDC 團隊的壓力越來越大，要求他們說點什麼，即使沒有所有的事實。因此，科學家們決定在廣播中討論他們對猴痘是病因的懷疑。他們建議人們在出現任何症狀時挺身而出。
賭贏了。他們不僅對猴痘的看法是正確的，而且他們的公開信息還揭示了社區中的其他病例。在一年內，他們確定了 122 例確診和疑似病例，以及 7 例死亡病例。近 70% 的病例發生在男性身上，其中許多是成年人，這表明 1980 年代天花疫苗賦予的免疫力在這一群體中正在減弱。該團隊還了解了為什麼猴痘似乎在這麼久之後突然在奈及利亞再次出現——事實證明這種疾病從未真正消失過。
Anne Rimoin 在剛果民主共和國研究流行病學 20 年。圖片來源：Anne W. Rimoin
「我們當時發現，我們可能在 2017 年之前遺漏了一些案例」，Yinka-Ogunleye 說。 一位與 NCDC 團隊交談的皮膚科醫生描述了她處理過的類似病例，但從未將猴痘視為病因。 該團隊得出結論，該病毒可能在奈及利亞流行。
Yinka-Ogunleye 推動改進對人類疾病的追踪和可能的動物宿主的識別。「她為協調全國的反應做了很多工作。 我們從她身上學到了很多」，NCDC 猴痘緊急行動中心的事件經理 Odianosen Ehikhamenor 說。 與此同時，在該領域工作近十年後，Yinka-Ogunleye 正在倫敦大學學院攻讀流行病學和全球衛生博士學位。
疾病差異
剛果民主共和國的猴痘病毒的發展軌跡與奈及利亞的不同。 在剛果民主共和國傳播的毒株來自於比奈及利亞和世界其他地方的病毒更致命的病毒「進化枝」，而且由於持續的衝突，剛果民主共和國的衛生基礎設施不那麼健全。 自 1980 年代以來，該國每年都有數千例疑似猴痘病例和數百人死於該病。 2022年至今，該國衛生部報告了4,500多例疑似和確診病例，155例死亡。 儘管剛果民主共和國缺乏足夠的實驗室資源來確認大多數病例，但 Rimoin 在過去二十年一直致力於改變這一狀況。
她走的是一條意想不到的路。「我主修非洲歷史」，她說。「我的論文是關於帕特里斯·盧蒙巴 (Patrice Lumumba) 的被暗殺」，剛果民主共和國的第一任總理。 隨著她對這個國家的文化和政治有了更多的了解，她開始對可以幫助那裡的人的方式產生興趣。
歷史專業畢業後，她在馬里蘭州巴爾的摩的約翰霍普金斯大學彭博公共衛生學院攻讀公共衛生碩士學位，並獲得流行病學博士學位。 從那以後，她致力於與剛果民主共和國的同事一起研究新興傳染病。 她說，她的目標是與「這些了不起的科學家」合作並提供支持。
非洲的猴痘：世界忽視的科學
自 2002 年以來，Rimoin 一直積極參與幫助剛果民主共和國的衛生工作者和研究人員改進檢測、監測和研究，同時透過她創立的加州大學洛杉磯分校-剛果民主共和國衛生研究和培訓項目協助其他非洲國家和地區的官員。 該計劃培訓來自美國和剛果民主共和國的流行病學家在資源匱乏、後勤複雜的環境中進行傳染病研究。
「她是一位優秀的科學家，擁有豐富的實地經驗，尤其是在猴痘方面」，金薩沙國家生物醫學研究所流行病學和全球衛生部主任 Placide Mbala 說。「與其他外國合作者不同」，他說，「她對新想法和建議非常開放」。
當英國傳出輸入性猴痘病例的消息時，Rimoin 說她並不感到驚訝。 她經常警告說，由於天花疫苗接種計畫的中斷，世界很容易感染這種病毒。 （與天花不同，由於動物宿主的存在，猴痘無法根除。）她經常討論病毒如何傳播到非洲以外地區。
寂靜的傳播
由於猴痘現在被世界衛生組織視為全球公共衛生緊急事件，Yinka-Ogunleye 和 Rimoin 表示，對這種疾病在非洲的嚴重程度進行研究的需求從未如此強烈。 猴痘在至少八個國家流行，包括貝南、喀麥隆、加納和賴比瑞亞，在當前全球爆發期間，這些國家和整個非洲大陸的其他國家都報告了病例。
Yinka-Ogunleye 說，血清盛行率研究——對病毒有抗體的人數——是了解奈及利亞和整個非洲爆發的真實程度的關鍵優先事項。 她說，這將揭示暴露的人數比例。
Yinka-Ogunleye 和 Rimoin 同意需要更多支持疾病監測，包括實驗室診斷。 在剛果民主共和國，將樣本從發生病例的任何地方運送到金薩沙等大城市是很困難的，如果不是不可能的話。
Rimoin 還呼籲提供更好的資源，以幫助了解所有流行地區的病毒流行病學和生態學。
「我們還有很多需要了解的地方」，她說。 這包括以前接觸猴痘後的免疫力持續多長時間、不良後果的風險因素、人與人之間傳播的性質以及病毒在不同環境下表面的穩定性。 Rimoin 說，儘管還有很長的路要走，但她希望她的合作者網絡和進一步研究的推出將加快進展。 「我們希望得到答案」，她說。
《自然》 612, 22-23 (2022) ；doi: https://doi.org/10.1038/d41586-022-04155-9
參考文獻：
1.Yinka-Ogunleye, A. et al. Lancet Infect. Dis. 19, 872–879 (2019).
2.Weinstein, R. A., Nalca, A., Rimoin, A. W., Bavari, S. & Whitehouse, C. A. Clin. Infect. Dis. 41, 1765–1771 (2005).
3.Rimoin, A. W. et al. Proc. Natl Acad. Sci. USA 107, 16262–16267 (2010).
These monkeypox researchers warned that the disease would go global
A Nigerian disease-surveillance expert and a US epidemiologist have been tracking monkeypox for years. Can their insights help to stop its spread and prevent future outbreaks?
Paul Adepoju / NEWS FEATURE / 30 November 2022
Adesola Yinka-Ogunleye led Nigeria’s investigation into a monkeypox outbreak in 2017. Credit: Alecsandra Dragoi for Nature
In May, when monkeypox began to spread across Europe and beyond, many public-health specialists were taken by surprise. But for researchers who have tracked and studied the viral disease for years in Central and West Africa, the only shock was seeing how accurate their predictions were.
“We had always warned that in favourable circumstances, like what led to this outbreak, the disease could pose a great threat to global health,” says Adesola Yinka-Ogunleye, an epidemiologist at the Nigeria Centre for Disease Control (NCDC) in Abuja, who led the country’s investigation and response to a 2017 monkeypox outbreak.
What does the future look like for monkeypox?
Now, with more than 80,000 confirmed cases in over 100 countries, monkeypox is a stark reminder of what happens when such warnings go unheeded. Scientists such as Yinka-Ogunleye and epidemiologist Anne Rimoin, who has worked on monkeypox outbreaks in the Democratic Republic of the Congo (DRC) since 2002, have amassed decades of experience investigating how the virus spreads. Their fieldwork has helped to inform the global response, and yet much more remains to be uncovered. “There are lots of questions that we need to answer,” says Rimoin, who is based at the University of California, Los Angeles (UCLA).
Nature talked to both researchers to understand how the virus gained its hold in Africa, and what can be done to stem its spread and prevent future global outbreaks of the disease.
Mystery malady
In September 2017, Yinka-Ogunleye and her team travelled to Bayelsa in southern Nigeria to investigate the appearance in people of mysterious skin rashes that were defying treatment. The team suspected that the rashes were due to monkeypox — a virus related to variola, which causes smallpox. But the country hadn’t recorded a case of monkeypox in about 40 years; it was a condition that doctors and medical students at the time had never encountered. On the basis of the symptoms they were seeing, the researchers first had to rule out smallpox.
Testing could not be done in Nigeria, however, and would take several weeks. In the meantime, word of their investigation leaked, and the public started to become alarmed about a potential health crisis. Pressure was mounting for the NCDC team to say something, even without all the facts. So, the scientists decided to go on the radio and discuss their suspicion that monkeypox was the cause. They advised people to come forward if they experienced any symptoms.
The gamble paid off. Not only were they right about monkeypox, their public messaging revealed additional cases in the community. In a year, they identified 122 confirmed and probable cases, and 7 deaths. Nearly 70% of the cases were in men, many of whom were adults, suggesting that immunity conferred by the smallpox vaccine in the 1980s was waning in this group. The team also learnt why monkeypox seemed to suddenly reappear in Nigeria after so long — it turns out the disease had never truly vanished.
Anne Rimoin has studied epidemiology in the Democratic Republic of the Congo for 20 years.Credit: Anne W. Rimoin
“We found at the time that perhaps we missed some cases prior to 2017,” Yinka-Ogunleye says. One of the dermatologists who spoke to the NCDC team described similar cases she had managed, but without ever considering monkeypox as the cause. The team concluded that the virus was probably endemic in Nigeria.
Yinka-Ogunleye pushed to improve tracking of the disease in humans and identification of possible animal reservoirs. “She did a lot to coordinate the national response. We have learnt a lot from her,” says Odianosen Ehikhamenor, incident manager at the NCDC’s Monkeypox Emergency Operations Centre. Meanwhile, after working in the field for nearly a decade, Yinka-Ogunleye is studying for a doctorate in epidemiology and global health at University College London.
Disease differences
Monkeypox in the DRC has followed a different trajectory from that in Nigeria. The strain circulating in the DRC is descended from a ‘clade’ of the virus that is more deadly than the one in Nigeria and the rest of the world, and the DRC’s health infrastructure is less robust as a result of continuing conflicts. The country has seen thousands of cases of suspected monkeypox and hundreds of deaths from the disease each year since the 1980s. In 2022 so far, the country’s health ministry has reported more than 4,500 suspected and confirmed cases and 155 deaths. Although the DRC lacks sufficient laboratory resources to confirm most cases, Rimoin has been working to change that for the past two decades.
She came to the field by an unexpected route. “I was an African history major,” she says. “My thesis was on the assassination of Patrice Lumumba,” the DRC’s first prime minister. As she learnt more about the country’s culture and politics, she became interested in ways that she could help people there.
After graduating in history, she did a master’s in public health that led to a doctorate in epidemiology at Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland. From there, she dedicated herself to working on emerging infectious diseases with colleagues in the DRC. Her goal, she says, was to collaborate with and support “these incredible scientists”.
Monkeypox in Africa: the science the world ignored
Since 2002, Rimoin has been actively involved in helping health workers and researchers in the DRC to improve testing, surveillance and research, while assisting officials from other African countries and regions through the UCLA–DRC Health Research and Training programme that she founded. The initiative trains epidemiologists from the United States and the DRC to conduct infectious-disease research in low-resource, logistically complex settings.
“She is a good scientist with great field experience, especially on monkeypox,” says Placide Mbala, head of epidemiology and global health at the National Institute of Biomedical Research in Kinshasa. “Unlike other foreign collaborators,” he says, “she is very open to new ideas and to suggestions.”
When news broke of imported cases of monkeypox in the United Kingdom, Rimoin says she was not surprised. She has often warned that the world is susceptible to this virus, owing to discontinuation of smallpox vaccination programmes. (Unlike smallpox, monkeypox cannot be eradicated because of the existence of animal reservoirs.) She has frequently discussed how the virus could spread beyond Africa.
Silent spread
With monkeypox now considered by the World Health Organization as a global public-health emergency, Yinka-Ogunleye and Rimoin say there has never been a greater need for studies of the disease’s magnitude in Africa. Monkeypox is endemic in at least eight countries, including Benin, Cameroon, Ghana and Liberia, and cases have been reported in these countries and in others across the continent during the current global outbreak.
Yinka-Ogunleye says that studies of seroprevalence — the number of people who have antibodies to the virus — are a key priority for understanding the true extent of the outbreak in Nigeria and throughout Africa. This would reveal the proportion of people who have been exposed, she says.
Yinka-Ogunleye and Rimoin agree on the need for more support for disease surveillance, including laboratory diagnostics. In the DRC, transporting samples from wherever cases occur to a major city such as Kinshasa is difficult, if not impossible.
Rimoin also calls for better resources to help unpick the epidemiology and ecology of the virus in all endemic regions.
“There is still a lot that we need to understand,” she says. This includes how long immunity from previous exposures to monkeypox lasts, risk factors for poor outcomes, the nature of human-to-human transmission and the stability of the virus on surfaces in different settings. Rimoin says that, although there is a way to go, she hopes her network of collaborators and the roll-out of further studies will speed progress. “We hope to get answers,” she says.
Nature 612, 22-23 (2022)
doi: https://doi.org/10.1038/d41586-022-04155-9
References
1.Yinka-Ogunleye, A. et al. Lancet Infect. Dis. 19, 872–879 (2019).
2.Weinstein, R. A., Nalca, A., Rimoin, A. W., Bavari, S. & Whitehouse, C. A. Clin. Infect. Dis. 41, 1765–1771 (2005).
3.Rimoin, A. W. et al. Proc. Natl Acad. Sci. USA 107, 16262–16267 (2010).