英國男男性行為者接種淋病疫苗的可行性
資料來源:www.thelancet.com/infection 2022 年 7 月 22 日 / 財團法人台灣紅絲帶基金會編譯
淋病感染是由淋病雙球菌引起的,主要透過性接觸傳播。據 WHO 估計,2020 年全球 15-49 歲人群中有 8240 萬人的新發感染。 WHO 提出了一個目標,即到 2030 年將淋病發生率從 2018 年之全球基準線水平降低 90%,作為其2016-21年全球衛生部門性傳播感染策略的一部分。根據世衛組織全球淋病球菌抗微生物藥物監測規劃,自 2009 年以來,淋病奈瑟氏球菌的多重耐藥性迅速增加,並大大減少了治療選擇。已經提出了各種新的預防策略來減少淋病的傳播,並且疫苗接種已被確定為優先選擇。一種現有的疫苗,旨在預防由腦膜炎奈瑟氏菌(B型流行性腦脊髓膜炎四成份疫苗 [4CMenB ] )被發現具有針對淋病奈瑟氏球菌的潛在交叉保護作用,且針對以4CMenB疫苗對抗淋病奈瑟氏球菌的人體臨床試驗正在進行中。針對性傳播感染 (STI) 疫苗,(包括淋病),的理論影響和成本效益進行建模概述,亦為世衛組織推進性傳播感染疫苗開發之全球路線圖中九個優先行動領域之一。
在《刺胳針傳染病》期刊中,Whittles 及其同事報告了他們基於動態傳播模型針對英格蘭之男男性行為者 (MSM) 接種 4CMenB 疫苗以預防淋病的潛在成本效益評估。本研究首次使用動態傳播模型而非靜態決策樹或馬爾可夫模型對新的淋病疫苗進行經濟評估,以說明疫苗接種對未來發生率的影響。值得注意的是,結果顯示在英格蘭的性健康診所使用 4CMenB 疫苗對 MSM 進行淋病疫苗接種可能具有成本效益。所推薦的根據風險接種疫苗策略 (vaccination-accordingto-risk, VaR strategy),該策略採取為門診就診時被診斷為淋病或是報告每年有五個以上性伴侶的 MSM 接種疫苗,根據淋病疫苗接種的健康經濟學分析,這是一種有價值的策略。
該研究發現,針對 MSM 中的淋病奈瑟氏球菌接種 4CMenB 疫苗可以節省成本,這是基於這樣的假設:4CMenB 疫苗的定價與其目前用於對抗腦膜炎奈瑟氏球菌的英國國家衛生服務之價格相似,並且對淋病奈瑟氏球菌具有療效類似於針對腦膜炎奈瑟球菌的結果(約 31%)。但還有幾個問題有待解決;首先,需要實驗性人體臨床試驗來確定 4CMenB 的實際疫苗效力,儘管現有文獻顯示 4CMenB 作為淋病奈瑟菌疫苗在生物學上是可行的(圖)。其次,鑑於 4CMenB 疫苗的療效相對較低,MSM 是否會廣泛接受該疫苗需要考慮。將擬議的疫苗納入現有的國家贊助之保險計畫將是一個不錯的選擇,以確保疫苗的成本不會阻礙疫苗接種策略的推出。第三,有必要進行試點先驅研究以驗證根據風險接種疫苗 (VaR) 方法的可行性。主要挑戰之一是在接種疫苗前應使用行為問卷或其他風險評估工具以準確地識別高風險之MSM。第四,疫苗接種不應取代其他初級預防措施(例如,使用保險套),應監測由於接種疫苗後的風險補償所引起高風險性行為之增加。第五,若要將研究結果推廣到其他人群(例如,異性戀人群)和淋病篩查並非常規做法的低收入國家之環境時將需要進一步的調查。
實現世衛組織 2030 年將淋病發病率降低 90% 的目標面臨挑戰。然而,即使是部分保護性的疫苗仍然可以防止很大一部分高危人群感染淋病,從而防止進一步的傳播。當感染確實發生時,接種過疫苗者的人體內的淋病奈瑟氏菌載量可能仍會減少,這些感染者可能比未接種疫苗的人更容易接受抗生素治療。政策制定者應考慮將 4CMenB 疫苗作為預防和控制淋病的潛在選擇,以便在現成可用的更有效方法取得之前努力以實現 2030 年目標。
Whittles 及其同事的研究基於動態模型藉由不同的疫苗效力、保護持續時間、疫苗攝取水平和 MSM 中的性行為等評估了B型流行性腦脊髓膜炎四成份疫苗接種策略的人群效應和成本效益。該研究的關鍵信息是,根據目標 MSM 人群的風險使用 4CMenB 疫苗以進行疫苗接種可能具有成本效益,即使該疫苗的效力相對較低且保護持續時間較短。這種策略應該在英國這樣的高收入國家環境中得到推薦和推廣。
圖:根據淋病奈瑟菌風險策略進行 4CMenB 疫苗接種的潛在推出步驟示意圖
在實施淋病奈瑟菌的策略之前,需要進行人體臨床試驗以確定 4CMenB 疫苗的功效,然後接續進行疫苗在目標人群中的可接受性之評估調查。精準地確認高風險之目標群體是確保策略可行性的關鍵。此外,策略應與其他預防措施相整合,並推廣到其他環境中。
我們聲明沒有競爭利益。
沉明旺,*張磊 lei.zhang1@monash.edu
中國陝西省西安市,交通大學醫學部公共衛生學院,中澳傳染病聯合研究中心 (MS, LZ) ; 中國陝西省西安市疾病預防控制與健康促進重點實驗室(MS);澳大利亞維多利亞州墨爾本,墨爾本性健康中心,Alfred Health(LZ);澳大利亞維多利亞州墨爾本,莫納什大學,醫學、護理和健康科學學院,中央臨床學院 (LZ);中國河南省鄭州市,鄭州大學公共衛生學院,流行病學與生物統計學系(LZ)
Feasibility of gonorrhoea vaccination among men who have sex with men in England
www.thelancet.com/infection Vol 22 July 2022
Gonorrhoea infection is caused by Neisseria gonorrhoeae bacteria and is mainly transmitted through sexual contact. According to WHO estimates, 82·4 million new infections occurred worldwide among people aged 15–49 years in 2020. WHO proposed a target of a 90% reduction in gonorrhoea incidence by 2030, from a 2018 global baseline, as part of its global health sector strategy on sexually transmitted infections for 2016–21. Multidrug resistance in N gonorrhoeae has increased rapidly since 2009, according to the WHO Global Gonococcal Antimicrobial Surveillance Programme, and has substantially reduced options for treatment. Various novel preventive strategies have been proposed to reduce the transmission of gonorrhoea, and vaccination has been identified as a priority option. One existing vaccine, designed to protect against meningococcal disease caused by Neisseria meningitidis (the four-component serogroup B meningococcal [4CMenB] vaccine), was found to have potential crossprotection against N gonorrhoeae, and human clinical trials of 4CMenB against N gonorrhoeae are underway. Modelling the theoretical impact and cost-effectiveness of vaccines against sexually transmitted infections (STIs), including gonorrhoea, was outlined as one of nine priority action areas in WHO’s global roadmap for advancing STI vaccine development.
In The Lancet Infectious Diseases, Whittles and colleagues report on their assessment of the potential cost-effectiveness of 4CMenB vaccination against gonorrhoea among men who have sex with men (MSM) in England, based on a dynamic-transmission model. This study is the first economic evaluation of a novel gonorrhoea vaccine to use a dynamic-transmission model, rather than the static decision tree or Markov model, to account for the impact of vaccination on future incidence rates. Notably, the results suggested that gonorrhoea vaccination for MSM using the 4CMenB vaccine in sexual health clinics in England was likely to be cost-effective. The recommended vaccination-accordingto-risk (VaR) strategy, which involves vaccinating MSM attending clinics who have a gonorrhoea diagnosis or who report having more than five sexual partners per years, represents a valuable strategy in light of the healtheconomic analysis of gonorrhoea vaccination.
The study’s finding that 4CMenB vaccination for N gonorrhoeae in MSM would be cost-saving is based on the assumption that the 4CMenB vaccine would be priced similarly to its current UK National Health Service price for use against N meningitidis, and have an efficacy against N gonorrhoea similar to that against N meningitidis (around 31%). Several questions remained to be addressed. First, empirical human clinical trials would be required to determine the actual vaccine efficacy of 4CMenB, although the existing literature suggests that 4CMenB as a vaccine for N gonorrhoeae would be biologically feasible (figure). Second, whether MSM will widely accept the 4CMenB vaccine, given a relatively low efficacy, needs to be considered. Integrating the proposed vaccine into the existing state-sponsored insurance scheme would be a good option to ensure the cost of the vaccine would not hinder the rollout of the vaccination strategy. Third, pilot studies are necessary to verify the feasibility of the VaR approach. One of the main challenges is identifying high-risk MSM accurately using behavioural questionnaires or other risk-assessment tools before vaccination. Fourth, vaccination should not replace other primary prevention measures (eg, condom use), and the potential increase in high-risk sexual behaviour due to risk compensation after vaccination should be monitored. Fifth, generalising the findings to other populations (eg, heterosexual population) and to settings in lower-income countries where screening for gonorrhoea is not a routine practice will require further investigation.
Achieving WHO’s 2030 target of reducing gonorrhoea incidence by 90% is subject to challenges. However, even a partially protective vaccine could still prevent a substantial proportion of high-risk individuals from gonorrhoea infection and hence further rounds of transmission. When infections do occur, people who have been vaccinated might still have a reduced withinhost load of N gonorrhoeae and these infections might be more susceptible to antibiotic treatments than those in unvaccinated people. Policy makers should consider the 4CMenB vaccine as a potential option for gonorrhoea prevention and control in the effort of achieving the 2030 target before a more effective approach becomes readily available.
Whittles and colleagues’ study evaluated the population effects and cost-effectiveness of four gonorrhoea vaccination strategies with varying vaccine efficacy, duration of protection, levels of vaccine uptake, and sexual behaviour in MSM based on a dynamic model. The key message of the study is that vaccination using the 4CMenB vaccine according to the risk of the targeted MSM population is likely to be costeffective, even if the vaccine were to have a relatively low efficacy and a short duration of protection. Such a strategy should be recommended and rolled out in a high-income country setting such as England.
We declare no competing interests.
Mingwang Shen, *Lei Zhang lei.zhang1@monash.edu
China-Australia Joint Research Center for Infectious Diseases, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061, China (MS, LZ); Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi’an, Shaanxi, China (MS); Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC, Australia (LZ); Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia (LZ); Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China (LZ)