疫苗施打與高風險群風險意識對美國 2022-2023 M痘疫情的防治效果：傳染病數理建模研究

Abstract

背景： 2022 年開始的M痘（mpox）全球爆發流行帶來前所未有的公共衛生挑戰。因應M痘疫情，美國除推動全國MVA-BN ( JYNNEOS®) 疫苗接種計畫外，亦有社區組織與公衛機構進行衛教宣導風險與隨後的高風險族群性行為風險降低之行為改變。本研究透過建構風險結構分層之M痘數理模型，估計上述兩項防疫介入措施對美國M痘疫情的防治效果，以及是否有協同作用。

方法： 本研究建構「易感-潛伏-症狀前期-有症狀感染期-無症狀-康復-接種（SEIARV）」確定性分室模型 (deterministic compartmental model)，並根據M痘傳播風險將模型人口分層為高風險群與低風險群，其中高風險為13歲以上，具有透過危險性行為而感染M痘風險的男男間性行為者 (men who have sex with men, MSM)。模型結構依據M痘傳播感染自然史以及2劑疫苗施打過程，區分為 11 個分室。模型參數依據文獻資料、CDC 通報數據、疫苗接種統計與行為問卷調查推估，並使用平方根轉換的最小平方法擬合 2022 年 5 月 22 日至 12 月 22 日間美國每日通報猴痘病例數來估計3項參數：M痘傳播系數、具感染力之分室的初始人數、高風險群人口佔比。藉由模擬四種情境（無介入措施、只實施疫苗接種、只具備行為改變、兩者共同實施），本研究計算各情境下累積通報病例數與感染數之差異，以評估各措施的預防百分比成效。另外也進行單變項與多變項敏感度分析，以了解該參數之不確定性對預防百分比結果估計的影響。

結果： 模型估計高風險與低風險族群之基本再生數分別為 3.88 與 0.39，並成功重建疫情曲線，預測期間累積通報病例數為 29,559（28,081, 31,036），其中 71.8% 為高風險族群，與實際通報資料中 16–45 歲男性佔比（78.6%）相近。若無衛教，在緊迫時間內所能完成的疫苗接種劑數僅能預防 21.2%（10.2%–24.1%）病例；若無疫苗接種，僅靠衛教與高風險群危機意識導致的性行為改變只能預防 15.4%（14.3%–20.6%）病例；兩者同時實施時則可預防 64.0%（43.8%–69.0%）病例，顯示疫苗與行為改變間產生協同作用。敏感度分析結果顯示，疫苗保護力與通報率的高低對預防百分比估計值有較大的影響；然而，所有情境中疫苗與行為改變皆呈現協同作用而非單純累加效應。

結論： 本研究指出，儘管疫苗覆蓋率與行為改變程度皆有限，但兩者的共同實施在控制 2022–2023 年美國M痘疫情中發揮協同作用。高風險族群之風險意識提升和減少危險性行為，在群體層面可迅速降低傳播率，進而爭取時間讓疫苗施打的覆蓋率提高並帶來相對更持久的個體層級之免疫保護，兩者產生協同作用，成功防治美國M痘疫情。此結果也可望普遍應用於其他可透過疫苗預防和行為介入防治的傳染病，對未來新興傳染病防治策略提供重要參考。

Background The unprecedented global outbreak of mpox in 2022 posed a public health challenge. In addition to the mpox vaccine campaign in the United States (US), community organizations and public health agencies initiated educational efforts to promote sexual risk reduction. This modelling study estimated the impact of the two-dose vaccination campaign and sexual behavior changes coincident with high-risk group awareness on the mpox epidemic in the US.

Method We constructed a deterministic, risk-structured “susceptible-exposed-infectious- asymptomatic-recovered-vaccinated” (SEIARV) model based on careful parameter estimations using results from survey studies, national-wide statistics on mpox cases, and data on vaccine administration, and fitted our model to the epidemic curve of reported mpox cases in the US between May 22, 2022 to December 22, 2022. We evaluated the putative effects of the two preventive responses in the US -- vaccination and sexual risk reduction -- at the population-level, by calculating the prevention percentages of cumulative cases compared to the counterfactual scenario without interventions. We performed sensitivity analyses with four parameters: case reporting fidelity, vaccine effectiveness, proportion of asymptomatic cases, and assortative mixing.

Result Model fitting revealed a basic reproduction number of 3.88 and 0.39 for the high-risk and low-risk populations, respectively. Model simulated a total of 29,559 (28,081, 31,036) mpox reported cases between May 22 and December 22, 2022. An estimated 71.8% of mpox cases was from the high-risk population, which is comparable to the actual distribution of cases in the United States among males aged 16–45 years (78.6%), a demographic most actively engaged in sexual activity. A two-dose vaccination campaign, solely, could prevent 21.2% (10.2%–24.1%) of cases, while behavior changes due to high-risk group awareness alone could prevent 15.4% (14.3%–20.6%). The combination of both measures were synergistic, with the model suggesting that 64.0% (43.8%–69.0%) of US cases were averted that would have otherwise occurred. In the sensitivity analyses, the proportion of mpox cases reported in the US and the proportion of asymptomatic cases had some effect on the estimates of prevention percentage for the preventive measures individually, and for the combination of both measures. However, in all scenarios, the vaccination campaign and high-risk group awareness demonstrated synergistic effects.

Conclusion Our models suggest that the 2022-2023 mpox epidemic in the US was controlled by a combination of two-dose mpox vaccination campaign and high-risk group awareness and sexual risk reduction. Awareness-associated behavior adaptations can quickly reduce transmission across the population at risk, thus buy time for the vaccination campaign to catch up to provide more durable protection to maximize the prevention proportions. This principle can be applied to preparedness and response to other vaccine-preventable and behaviorally mediated infectious diseases.