预防对于降低发病率和死亡率至关重要,因为目前除了支持治疗外,在黄热病管理方面没有其他治疗方法。 接种疫苗和防止蚊子咬伤是建议的预防策略。
对于年龄≥9 月龄、居住在有黄热病传播风险区域(例如,非洲、南美洲)或前往该区域旅行的人群,推荐接种 17D 减毒活疫苗。应至少在旅行之前 10 天接种疫苗。[16]Staples JE, Bocchini JA Jr, Rubin L; Centers for Disease Control and Prevention (CDC). Yellow fever vaccine booster doses: recommendations of the Advisory Committee on Immunization Practices, 2015. MMWR Morb Mortal Wkly Rep. 2015;64:647-650.https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6423a5.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26086636?tool=bestpractice.com鉴于巴西目前暴发的疫情,截至 2018 年 5 月 3 日,世界卫生组织 (WHO) 推荐前往以下地区的国际旅行者接种黄热病疫苗:巴西圣埃斯皮里图州、圣保罗或里约热内卢的任何地区;巴伊亚的某些地区;巴拉那州、圣卡塔琳娜州和南里奥格兰德州;或其他有传播风险的地区。[17]World Health Organization. Updates on yellow fever vaccination recommendations for international travelers related to the current situation in Brazil. May 2018 [internet publication].http://www.who.int/ith/updates/20180503/en/
CDC: yellow fever travel information
有感染风险的实验室工作者也应当接种疫苗。[16]Staples JE, Bocchini JA Jr, Rubin L; Centers for Disease Control and Prevention (CDC). Yellow fever vaccine booster doses: recommendations of the Advisory Committee on Immunization Practices, 2015. MMWR Morb Mortal Wkly Rep. 2015;64:647-650.https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6423a5.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26086636?tool=bestpractice.com
WHO 目前推荐单剂初次疫苗接种(皮下注射),可产生终生免疫力。不再要求 10 年加强接种。[18]Gotuzzo E, Yactayo S, Córdova E. Efficacy and duration of immunity after yellow fever vaccination: systematic review on the need for a booster every 10 years. Am J Trop Med Hyg. 2013;89:434-444.http://www.ncbi.nlm.nih.gov/pubmed/24006295?tool=bestpractice.com 然而,虽然美国疾病预防控制中心 (Centers for Disease Control and Prevention, CDC) 免疫实践咨询委员会 (Advisory Committee on Immunization Practices, ACIP) 同意这对大多数旅行者已经足够,但建议下列旅行人群接受额外接种:[16]Staples JE, Bocchini JA Jr, Rubin L; Centers for Disease Control and Prevention (CDC). Yellow fever vaccine booster doses: recommendations of the Advisory Committee on Immunization Practices, 2015. MMWR Morb Mortal Wkly Rep. 2015;64:647-650.https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6423a5.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26086636?tool=bestpractice.com
此外,ACIP 建议,对于在≥10 年前接种末次疫苗并且根据地区、季节、旅行持续时间和活动(例如在流行区长时间停留)将处于较高风险环境的人群,可以考虑接种加强剂量。 操作病毒的实验室工作者,应当至少每 10 年进行一次抗体滴度测定,确定他们是否应当接种额外剂量的疫苗。[16]Staples JE, Bocchini JA Jr, Rubin L; Centers for Disease Control and Prevention (CDC). Yellow fever vaccine booster doses: recommendations of the Advisory Committee on Immunization Practices, 2015. MMWR Morb Mortal Wkly Rep. 2015;64:647-650.https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6423a5.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26086636?tool=bestpractice.com 并非所有的机构都认同 WHO 对现有数据的解读。[19]Grobusch MP, Goorhuis A, Wieten RW, et al. Yellow fever revaccination guidelines change - a decision too feverish? Clin Microbiol Infect. 2013;19:885-886.http://www.ncbi.nlm.nih.gov/pubmed/23927031?tool=bestpractice.com
WHO 建议,如果疫苗短缺,可以使用常规剂量的 1/5(部分剂量)来控制爆发。[20]World Health Organization Department of Immunization, Vaccines and Biologicals. Fractional dose yellow fever vaccine as a dose-sparing option for outbreak response. July 2016 [internet publication].http://apps.who.int/iris/bitstream/10665/246236/1/WHO-YF-SAGE-16.1-eng.pdf?ua=1在纳入 493 名参与者的一项临床试验中,小剂量接种可有效诱导 98% 的基线血清反应呈阴性患者的血清转换。[21]Ahuka-Mundeke S, Casey RM, Harris JB, et al. Immunogenicity of fractional-dose vaccine during a yellow fever outbreak - preliminary report. N Engl J Med. 2018 Feb 14.https://www.nejm.org/doi/10.1056/NEJMoa1710430?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.govhttp://www.ncbi.nlm.nih.gov/pubmed/29443626?tool=bestpractice.com一项长期研究发现, 分次接种在98%的疫苗接种者中,可诱导超过10年的保护性反应 (而若接受标准剂量接种,则此类患者比例为 97%)。[22]Roukens AHE, van Halem K, de Visser AW, et al. Long-term protection after fractional-dose yellow fever vaccination: follow-up study of a randomized, controlled, noninferiority trial. Ann Intern Med. 2018 Nov 27 [Epub ahead of print].http://www.ncbi.nlm.nih.gov/pubmed/30476963?tool=bestpractice.com
该疫苗禁用于以下人群:年龄<6 月龄的婴儿、对任何疫苗成分过敏的人(如果认为有必要免疫接种,可进行脱敏)、伴有免疫细胞功能异常的胸腺疾病患者、症状性 HIV 感染者或 CD4 计数<200 个细胞/mm³ (或者在年龄<6 岁的儿童中 CD4 计数<总数的15%)、原发性免疫缺陷患者、恶性肿瘤患者、进行移植的患者以及进行免疫抑制或免疫调节治疗的患者。对于 6-8 月龄的婴儿、≥60 岁的成人、无症状性 HIV 感染者和 CD4 计数为 200-499 个细胞/mm³ 的患者(或者计数为总数的 15%-24% 的年龄<6 岁的儿童),以及孕妇或正在进行母乳喂养的女性,应谨慎使用该疫苗。[8]Centers for Disease Control and Prevention (CDC). CDC health information for international travel (Yellow Book). Chapter 3: infectious diseases related to travel - yellow fever. March 2018 [internet publication].https://wwwnc.cdc.gov/travel/yellowbook/2018/infectious-diseases-related-to-travel/yellow-fever
已经发现,同时接种黄热病疫苗和麻疹-腮腺炎-风疹三联疫苗可导致相互干扰,两种疫苗的血清转换率均低于预期。[23]Nascimento Silva JR, Camacho LA, Siqueira MM, et al; Collaborative Group for the Study of Yellow Fever Vaccines. Mutual interference on the immune response to yellow fever vaccine and a combined vaccine against measles, mumps and rubella. Vaccine. 2011;29:6327-6334.http://www.ncbi.nlm.nih.gov/pubmed/21640779?tool=bestpractice.com 活病毒疫苗应同时给予或间隔至少 30 天。[8]Centers for Disease Control and Prevention (CDC). CDC health information for international travel (Yellow Book). Chapter 3: infectious diseases related to travel - yellow fever. March 2018 [internet publication].https://wwwnc.cdc.gov/travel/yellowbook/2018/infectious-diseases-related-to-travel/yellow-fever
虽然认为这种疫苗安全有效,但曾经报告过严重的不良反应,包括疫苗相关性嗜内脏性疾病(与野生型疾病类似的一种疾病)和神经系统疾病(例如:脑膜脑炎、吉兰-巴雷综合征、急性播散性脑脊髓炎、颅神经麻痹)。[16]Staples JE, Bocchini JA Jr, Rubin L; Centers for Disease Control and Prevention (CDC). Yellow fever vaccine booster doses: recommendations of the Advisory Committee on Immunization Practices, 2015. MMWR Morb Mortal Wkly Rep. 2015;64:647-650.https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6423a5.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26086636?tool=bestpractice.com[24]Thomas RE, Lorenzetti DL, Spragins W, et al. Active and passive surveillance of yellow fever vaccine 17D or 17DD-associated serious adverse events: Systematic review. Vaccine. 2011;29:4544-4555.http://www.ncbi.nlm.nih.gov/pubmed/21549787?tool=bestpractice.com 根据一份全面综述,这些事件的发生率约为每百万剂 0 至 14.6 例;但在≥60 岁的人群及免疫功能受损人群中,并发症的发生率增高。[24]Thomas RE, Lorenzetti DL, Spragins W, et al. Active and passive surveillance of yellow fever vaccine 17D or 17DD-associated serious adverse events: Systematic review. Vaccine. 2011;29:4544-4555.http://www.ncbi.nlm.nih.gov/pubmed/21549787?tool=bestpractice.com 更常见的不良反应包括轻度全身效应,例如低热、头痛和肌痛。[8]Centers for Disease Control and Prevention (CDC). CDC health information for international travel (Yellow Book). Chapter 3: infectious diseases related to travel - yellow fever. March 2018 [internet publication].https://wwwnc.cdc.gov/travel/yellowbook/2018/infectious-diseases-related-to-travel/yellow-fever 针对多发性硬化症 (multiple sclerosis, MS) 患者接种黄热病疫苗的小型研究表明,MS 加重的风险升高,因此强调在推荐黄热病疫苗接种时,需要仔细评估风险-获益比。[25]Farez MF, Correale J. Yellow fever vaccination and increased relapse rate in travelers with multiple sclerosis. Arch Neurol. 2011;68:1267-1271.http://www.ncbi.nlm.nih.gov/pubmed/21670384?tool=bestpractice.com该疫苗会使 50% 的患者出现低水平病毒血症。尽管该病毒血症通常不具有临床相关性,但可导致已妊娠或免疫功能受损的患者出现严重问题。[26]Traiber C, Coelho-Amaral P, Ritter VR, et al. Infant meningoencephalitis caused by yellow fever vaccine virus transmitted via breastmilk. J Pediatr (Rio J). 2011;87:269-272.http://www.ncbi.nlm.nih.gov/pubmed/21461453?tool=bestpractice.com[27]Barte H, Horvath TH, Rutherford GW. Yellow fever vaccine for patients with HIV infection. Cochrane Database Syst Rev. 2014;(1):CD010929.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010929.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24453061?tool=bestpractice.com
有些国家在入境前要求出示免疫接种的证据。[16]Staples JE, Bocchini JA Jr, Rubin L; Centers for Disease Control and Prevention (CDC). Yellow fever vaccine booster doses: recommendations of the Advisory Committee on Immunization Practices, 2015. MMWR Morb Mortal Wkly Rep. 2015;64:647-650.https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6423a5.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26086636?tool=bestpractice.com 完整的疫苗接种或预防国际证书终生有效,在 2016 年 6 月,已经删除了对 10 年加强接种的要求。尽管如此,医生和旅行者应当审查具体国家的入境要求。
WHO: countries with risk of yellow fever transmission and countries requiring yellow fever vaccination
PAHO/WHO: updated requirements for the International Certificate of Vaccination or Prophylaxis (ICVP) with proof of vaccination against yellow fever
防止蚊子咬伤
避免蚊虫叮咬可减少黄热病感染的风险。 应当指导旅行者在风险地区在皮肤的暴露部位使用驱虫剂以驱赶蚊子。 美国环保署 (Environmental Protection Agency, EPA) 登记注册的驱虫剂包括含二乙甲苯酚胺 (N,N-diethylmetatoluamide, DEET) 和派卡瑞丁的产品。 浓度为 30% ~ 50% 的 DEET 效力可维持几小时。 浓度为 7% 和 15% 的羟乙基哌啶羧酸异丁酯则需要更频繁地使用。 成人和 2 月龄以上儿童均建议使用浓度高达 50% 的 DEET 制剂。 2 月龄以下婴儿应使用带有蚊帐(带有弹性边缘以便扎紧)的婴儿车予以防护。 使用防晒霜时,应先涂抹防晒霜,再涂抹驱虫剂。 在一天结束上床睡觉前,应将驱虫剂洗净。
到流行区的旅行者应穿折边式长袖衬衫、长裤和帽子,以遮蔽皮肤的暴露部位。应将含氯菊酯(例如除虫菊酯)的驱虫剂或其他驱虫剂喷洒在衣物、鞋子、帐篷、蚊帐和其他用具上,以起到更好的保护作用。通常大部分驱虫剂经过一次清洗便可以从衣物和用具上去除,但是用氯菊酯处理的衣物经过 5 次清洗仍然有效。许多种类的蚊子的叮咬高峰时间是黄昏至黎明期间;然而,非洲最主要的黄热病媒介 - 埃及伊蚊却在白天进食。美国 CDC 建议,在有黄热病风险的地区,需格外小心,要在白天、夜晚和凌晨使用驱虫剂和防护性衣物,或在此时间段考虑避免户外活动。[28]Mirzaian E, Durham MJ, Hess K, et al. Mosquito-borne illnesses in travelers: a review of risk and prevention. Pharmacotherapy. 2010;30:1031-1043.http://www.ncbi.nlm.nih.gov/pubmed/20874041?tool=bestpractice.com