脊髓灰质炎疫苗序贯免疫程序的研究与应用进展

脊髓灰质炎(脊灰)是由脊灰病毒引起的急性肠道传染病,传播广泛,对儿童的健康和生命危害极大。口服脊灰减毒活疫苗(Oral Attenuated Poliovirus Vaccine,OPV)是全球消灭脊灰行动的首选疫苗,已使II型脊灰野病毒于1999年在全球消灭;但在极少情况下会发生疫苗相关麻痹型脊灰(Vaccine-associated Paralytic Poliomyelitis,VAPP)和疫苗衍生脊灰病毒(Vaccine-derived Poliovirus,VDPVs)病例。为了避免这些风险,许多国家常规免疫规划已不再单独使用OPV,而是改用脊灰灭活疫苗(Inactivated Polio Vaccine,IPV)。这些国家在OPV转换成IPV期间,大部分采用了先接种1~2剂IPV,再接种≥2剂OPV的序贯免疫程序。IPV-OPV序贯免疫方案可减少或预防VAPP,同时又能保持较高的体液免疫和肠道黏膜免疫力,能更好地阻断脊灰野病毒在自然界的循环。根据WHO建议,常规免疫规划中只使用OPV的国家应当调整脊灰免疫策略,引进至少1剂次IPV,采取IPV-OPV序贯免疫策略或联合使用OPV和IPV的策略。相信这些转变将会加快全球消灭脊灰野毒株的进程,对实现全球最终根除脊灰的目标具有重要的意义。     

2008年阿富汗和巴基斯坦消灭脊髓灰质炎的进展

全球共有4个国家从未阻断脊髓灰质炎（脊灰）野病毒（Wild Poliovirus,WPV）的流行,阿富汗和巴基斯坦是其中两个,这两个国家都存在着病毒宿主。2008年这两个国家开展了消灭Ⅰ型WPV（WPVⅠ）和ⅢWPV（WPVⅢ）的强化免疫活动,在活动中使用口服脊灰减毒活疫苗（Oral Poliomyelitis Attenuated Live Vaccine,OPV）。除去受战乱影响的南部地区外,2008年阿富汗大部分地区保持无脊灰病例发生。     

美国疾病预防控制中心对于前往或来自脊髓灰质炎野病毒感染国家关于接种脊髓灰质炎疫苗的临时指南

在疫苗前时代,感染脊髓灰质炎（脊灰）野病毒[Wild Poliovirus（PV）,WPV]在全球较为普遍,温带地区在夏季和秋季出现季节性高峰及流行。1955年灭活脊灰病毒疫苗（Inactivated PV Vaccine,IPV）和20世纪60年代口服脊灰减毒活疫苗（Oral Poliomyelitis Attenuated Live Vaccine,OPV）获得上市许可后,脊灰病例数在美国急剧下降。     

中国脊髓灰质炎疫苗使用历史回顾及免疫策略调整建议

在消灭脊髓灰质炎（脊灰）过程中,脊灰疫苗发挥了重要作用。口服脊灰减毒活疫苗（Oral Poliomyelitis Attenuated Live Vaccine,OPV）是一种安全有效的疫苗,中国于20世纪60年代推广使用OPV,常规免疫接种率逐步提高到〉90％。从1990年开始,部分省（自治区、直辖市）开展了OPV补充免疫活动（Supplementary Immunization Activity,SIA）;1993～2000年,开展消灭脊灰的国家免疫日活动,中国所在的世界卫生组织（World Health Organization,WHO）西太平洋区于2000年实现无脊灰的目标,继续在适龄儿童中加强OPV常规免疫和开展SIA。根据WHO制定的（（2013—2018年消灭脊灰终结战略计划》,2015年所有国家要引进至少1剂灭活脊灰病毒疫苗（Inactivated Poliovirus Vaccine,IPV）,2016年中期使用二价OPV（I＋Ⅲ型）,2018年停用OPV。为确保OPV成功转换IPV,中国应建立部门间协作机制,加快国产IPV研发生产进程,组织开展OPV和IPV转换的相关研究。     

患有严重联合免疫缺陷综合征的移民儿童患疫苗相关麻痹型脊髓灰质炎和播散性卡介苗病

<正>通过使用脊髓灰质炎(脊灰)灭活疫苗(Inactivated Poliovirus Vaccine,IPV)和口服脊灰减毒活疫苗(Oral Poliomyelitis Attenuated Live Vaccine,OPV),在世界上的大多数地区脊灰病毒的传播已被阻断。在美国,自2000年开始不再使用OPV,因为OPV可能导致疫苗相关麻痹型脊灰(Vaccine-associated Paralytic Poliomyelitis,VAPP);1980-     

使用脊髓灰质炎灭活疫苗的必要性及存在的问题

口服脊髓灰质炎（脊灰）减毒活疫苗（Oral Poliomyelitis Attenuated Live Vaccine,OPV）作为全球消灭脊灰的主要手段,在以发展中国家为中心的脊灰流行地区广泛使用。OPV有很多优点,其有效性、安全性、经济性都很显著,但同时也存在由于OPV本身的病毒学特性所引起的各种问题。因此,使用脊灰灭活疫苗（Inactivated Poliovirus Vaccine,IPV）替代OPV的必要性逐渐增加。现就替代OPV的疫苗,尤其是来自减毒的脊灰病毒的IPV,在日本及发展中国家使用的可能性和存在的问题加以论述。     

全球使用脊髓灰质炎病毒灭活疫苗的经验

口服脊髓灰质炎（脊灰）减毒活疫苗（Oral Poliomylitis AttenuateLive Vaccine,OPV）是全球消灭脊灰的战略,OPV已大幅度降低全球脊灰的发病率。然而,由于疫苗相关麻痹型脊灰（Vaccine Associated Paralytic Poliomyelitis,VAPP）和疫苗衍生脊灰病毒（Vac—cine-derived Poliovirus,VDPV）风险,今后必须停止0PV的使用,以彻底根除脊灰。     

中国脊髓灰质炎疫苗免疫策略的思考及建议

脊髓灰质炎(脊灰)曾在中国广泛流行,接种脊灰疫苗是消灭脊灰最有效的手段。脊灰有两种疫苗—口服脊灰减毒活疫苗(Oral poliomyelitis attenuated live vaccine,OPV)和脊灰灭活疫苗(Inactivated poliomyelitis vaccine,IPV)。两种疫苗的接种均可实现消灭脊灰野病毒(Wild poliovirus,WPV)的目标。目前全球WPV病例数已经达到历史最低水平,Ⅱ型疫苗衍生脊灰病毒(Type 2 vaccine-derived poliovirus,VDPV2)病例数远超过WPV病例数。为了最终实现消灭所有脊灰病例的目标,世界卫生组织提出全球最终将停止接种OPV,使用IPV的建议。本文根据全球消灭脊灰形势的变化,结合中国维持无脊灰工作进展和需要,提出中国脊灰疫苗免疫策略,即在保证国产IPV供应基础上,由目前的1剂IPV加3剂二价OPV(Bivalent oral polio vaccine,bOPV)的常规免疫程序,过渡到2剂IPV加2剂bOPV的免疫程序,直至全球消灭脊灰证实后,在常规免疫接种中停用bOPV,全程接种IPV。     

中国推进消灭脊髓灰质炎终结战略计划技术问题:世界卫生组织专家解读

中国积极推进消灭脊髓灰质炎(脊灰)终结战略计划,分阶段将灭活脊灰病毒疫苗(Inactivated Poliovirus Vaccine,IPV)纳入免疫规划,预期2016年4月与全球同步停服三价(Trivalent)口服脊灰减毒活疫苗(Oral Poliomyelitis Attenuated Live Vaccine,t OPV),开始接种二价(Bivalent)OPV(b OPV)。为澄清对一些技术问题的认识,世界卫生组织驻中国代表处会同国内外相关专家,讨论了中国部分专业人员提出的主要技术和政策问题,包括停用OPV的原因,b OPV替代t OPV使用的步骤,转换前减少风险的准备等,形成专家解读,供相关部门和专业人员在推进消灭脊灰终结战略计划中参考。     

后脊髓灰质炎时代我国应用赛宾株灭活脊髓灰质炎疫苗免疫的可行性

在所有国家被证实全部阻断了脊髓灰质炎(脊灰)野病毒传播后,全球将停止使用口服脊灰减毒活疫苗(Oral Poliomyelitis Attenuated Live Vaccine,OPV)免疫,进入后脊灰时代。为此,世界卫生组织(WHO)提出了届时全面停止OPV的使用,并同步开始灭活脊灰病毒疫苗(Inactivated Poliovirus Vaccine,IPV)的免疫,发展中国家更应考虑应用廉价的赛宾(Sabin)株IPV(sIPV)免疫,直至最终根除脊灰。然而目前全球尚无开发成功的sIPV上市。现介绍WHO推荐的这一免疫策略,分析全球sIPV的研发现状,从免疫策略、免疫程序、生产技术、疫苗供应等方面探讨我国应用sIPV免疫的可行性。鉴于这些可行性,我国应尽快推进sIPV的研发进程,为脊灰免疫策略的调整、实施做好准备。     

我国现阶段维持无脊髓灰质炎状态面临的挑战和对策

中国通过使用口服脊髓灰质炎（脊灰）减毒活疫苗（OralPoliomyelitisAttenuatedLiveVaccine,OPV）、加强OPV常规免疫和开展补充免疫活动,以及加强急性弛缓性麻痹（AcuteFlaccidParalysis,AFP）病例监测,消灭脊灰已取得了重大进展。1994年报告最后1例本土脊灰野病毒（WildPoliovirus,WPV）病例,2000年包括中国在内的世界卫生组织西太平洋区实现无脊灰目标。随后中国实施了维持无脊灰策略和措施,但2011年新疆维吾尔自治区发生了输入脊灰疫情。在现阶段中国维持无脊灰状态面临的挑战包括：WPV输入风险很大,疫苗衍生脊灰病毒（Vaccine—derivedPoliovirus,VDPV）和疫苗相关麻痹型脊灰病例时有发生,常规免疫存在薄弱环节,脊灰疫苗免疫策略需要调整。为继续维持无脊灰状态,直至全球消灭脊灰,中国要大力加强OPV常规免疫,适时引入脊灰病毒灭活疫苗和调整脊灰疫苗免疫策略,保持高水平AFP病例监测质量,及时和有效地处置可能发生的WPV输入和VDPV循环事件,开展WPV、VDPV及其感染或潜在感染性材料的封存和安全处理。     

Poliomyelitis prevention in the United States. Updated recommendations of the Advisory Committee on Immunization Practices (ACIP).

These recommendations of the Advisory Committee on Immunization Practices (ACIP) for poliomyelitis prevention replace those issued in 1997. As of January 1, 2000, ACIP recommends exclusive use of inactivated poliovirus vaccine (IPV) for routine childhood polio vaccination in the United States. All children should receive four doses of IPV at ages 2, 4, and 6-18 months and 4-6 years. Oral poliovirus vaccine (OPV) should be used only in certain circumstances, which are detailed in these recommendations. Since 1979, the only indigenous cases of polio reported in the United States have been associated with the use of the live OPV. Until recently, the benefits of OPV use (i.e., intestinal immunity, secondary spread) outweighed the risk for vaccine-associated paralytic poliomyelitis (VAPP) (i.e., one case among 2.4 million vaccine doses distributed). In 1997, to decrease the risk for VAPP but maintain the benefits of OPV, ACIP recommended replacing the all-OPV schedule with a sequential schedule of IPV followed by OPV. Since 1997, the global polio eradication initiative has progressed rapidly, and the likelihood of poliovirus importation into the United States has decreased substantially. In addition, the sequential schedule has been well accepted. No declines in childhood immunization coverage were observed, despite the need for additional injections. On the basis of these data, ACIP recommended on June 17, 1999, an all-IPV schedule for routine childhood polio vaccination in the United States to eliminate the risk for VAPP. ACIP reaffirms its support for the global polio eradication initiative and the use of OPV as the only vaccine recommended to eradicate polio from the remaining countries where polio is endemic.     

Managing population immunity to reduce or eliminate the risks of circulation following the importation of polioviruses

Poliovirus importations into polio-free countries represent a major concern during the final phases of global eradication of wild polioviruses (WPVs). We extend dynamic transmission models to demonstrate the dynamics of population immunity out through 2020 for three countries that only used inactivated poliovirus vaccine (IPV) for routine immunization: the US, Israel, and The Netherlands. For each country, we explore the vulnerability to re-established transmission following an importation for each poliovirus serotype, including the impact of immunization choices following the serotype 1 WPV importation that occurred in 2013 in Israel. As population immunity declines below the threshold required to prevent transmission, countries become at risk for re-established transmission. Although importations represent stochastic events that countries cannot fully control because people cross borders and polioviruses mainly cause asymptomatic infections, countries can ensure that any importations die out. Our results suggest that the general US population will remain above the threshold for transmission through 2020. In contrast, Israel became vulnerable to re-established transmission of importations of live polioviruses by the late 2000s. In Israel, the recent WPV importation and outbreak response use of bivalent oral poliovirus vaccine (bOPV) eliminated the vulnerability to an importation of poliovirus serotypes 1 and 3 for several years, but not serotype 2. The Netherlands experienced a serotype 1 WPV outbreak in 1992–1993 and became vulnerable to re-established transmission in religious communities with low vaccine acceptance around the year 2000, although the general population remains well-protected from widespread transmission. All countries should invest in active management of population immunity to avoid the potential circulation of imported live polioviruses. IPV-using countries may wish to consider prevention opportunities and/or ensure preparedness for response. Countries currently using a sequential IPV/OPV schedule should continue to use all licensed OPV serotypes until global OPV cessation to minimize vulnerability to circulation of imported polioviruses.     

End phase challenges of poliomyelitis eradication programme realization

The progress of poliomyelitis eradication programme realization, the implementation schedule and strategies for the future, are summarised based on publications of the World Health Organisation. During the following two years wild poliovirus strains should be globally eradicated. This means that potentially in 2010 the global eradication of wild polioviruses will be certified. To eradicate poliomyelitis, cessation of the oral polio vaccine (OPV) is necessary, since the vaccine strains produce cases of vaccine-associated paralytic poliomyelitis (VAPP) and cases of poliomyelitis caused by circulating vaccine-derived poliovirus (cVDPV). However, the WHO plan to stop immunization with OPV and the immunization with inactivated polio vaccine (IPV) shortly after, is alarming in the present situation. The article describes the measures undertaken to prevent or minimise the risk of reintroduction of wild poliovirus strains, which is potentially associated with WHO plan of action.     

Progress toward poliomyelitis eradication--India, January 2006-September 2007

India is one of four countries where wild poliovirus (WPV) transmission has never been interrupted (the others are Afghanistan, Nigeria, and Pakistan). An outbreak of poliomyelitis cases caused by WPV type 1 (WPV1) occurred in India in 2006, primarily in the northern states of Uttar Pradesh and Bihar, where polio remains endemic. This outbreak resulted in the greatest annual number of cases of poliomyelitis in India since 2002. In response, the Government of India and its partners implemented additional vaccination measures based on recommendations from the India Expert Advisory Group on Polio Eradication. These measures focused predominantly on use of monovalent oral poliovirus vaccine type 1 (mOPV1), which has higher efficacy against WPV1 than trivalent OPV (tOPV). As a result, WPV1 cases in India decreased approximately 84% to 66 cases during January-September 2007, compared with 405 cases during the corresponding period in 2006. In western Uttar Pradesh, a state in which multiple risk factors have made interruption of WPV transmission challenging, five WPV1 cases have been reported this year, compared with 299 during the same period in 2006. However, a WPV type 3 (WPV3) outbreak also has been reported, with 261 cases occurring through September 30, 2007, primarily in the northern states where polio remains endemic. This report summarizes progress toward polio eradication in India during January 2006-September 2007 and highlights the challenges and strategic adaptations of eradication measures.     

Imported vaccine-associated paralytic poliomyelitis--United States, 2005

Paralytic poliomyelitis is rare in the United States because of the success of universal childhood immunization and the Global Polio Eradication Initiative. Poliovirus vaccine was introduced in the 1950s. Since then, the United States has eliminated indigenous wild poliovirus transmission, controlled imported wild poliovirus cases, and, through a vaccine policy change (i.e., from live, attenuated oral polio vaccine [OPV] to inactivated polio vaccine [IPV]), eliminated vaccine-associated paralytic polio (VAPP) cases. The most recent VAPP case occurred in 1999. The primary risk for paralytic polio for U.S. residents is through travel to countries where polio remains endemic or where polio outbreaks are occurring. This report describes the first known occurrence of imported VAPP in an unvaccinated U.S. adult who traveled abroad, where she likely was exposed through contact with an infant recently vaccinated with OPV. This case highlights the previously unrecognized risk for paralytic polio among unvaccinated persons exposed to OPV during travel abroad.     

A developing country perspective on vaccine-associated paralytic poliomyelitis

When the Expanded Programme on Immunization was established and oral poliovirus vaccine (OPV) was introduced for developing countries to use exclusively, national leaders of public health had no opportunity to make an informed choice between OPV and the inactivated poliovirus vaccine (IPV). Today, as progress is made towards the goal of global eradication of poliomyelitis attributable to wild polioviruses, all developing countries where OPV is used face the risk of vaccine-associated paralytic poliomyelitis (VAPP). Until recently, awareness of VAPP has been poor and quantitative risk analysis scanty but it is now well known that the continued use of OPV perpetuates the risk of VAPP. Discontinuation or declining immunization coverage of OPV will increase the risk of emergence of circulating vaccine-derived polioviruses (cVDPV) that re-acquire wild virus-like properties and may cause outbreaks of polio. To eliminate the risk of cVDPV, either very high immunization coverage must be maintained as long as OPV is in use, or IPV should replace OPV. Stopping OPV without first achieving high immunization coverage with IPV is unwise on account of the possibility of emergence of cVDPV. Increasing numbers of developed nations prefer IPV, and manufacturing capacities have not been scaled up, so its price remains prohibitively high and unaffordable by developing countries, where, in addition, large-scale field experience with IPV is lacking. Under these circumstances, a policy shift to increase the use of IPV in national immunization programmes in developing countries is a necessary first step; once IPV coverage reaches high levels (over 85%), the withdrawal of OPV may begin.     

Global Polio Eradication Initiative Strategic Plan, 2004

Since the 1988 World Health Assembly resolution to eradicate poliomyelitis, the number of polio-endemic countries has decreased from 125 in 1988 to six in 2003 (i.e., Afghanistan, Egypt, India, Niger, Nigeria, and Pakistan), and the number of cases reported worldwide has decreased from approximately 350,000 to 682. In 2003, approximately 90% of cases were reported from Nigeria (305), India (220), and Pakistan (99); epidemiologic and virologic data demonstrated focal endemic transmission in Afghanistan and Niger, with repeated importations from Pakistan and Nigeria, respectively, and localized transmission in Egypt. On January 15, 2004, the World Health Organization (WHO) released an updated Global Polio Eradication Initiative Strategic Plan outlining activities required to 1) interrupt poliovirus transmission globally, 2) achieve global certification of polio eradication, and 3) prepare for global cessation of childhood vaccination with oral poliovirus vaccine (OPV). The discontinuation of mass vaccination campaigns in the majority of polio-free countries has left these areas vulnerable to importations of wild poliovirus (WPV) from the remaining countries in which polio is endemic. For polio to be eradicated, all remaining poliovirus reservoirs must be eliminated.     

The perspective of global eradication of poliomyelitis

In recent years, Germany and Switzerland have changed national policies to recommend vaccination with IPV (inactivated polio vaccine) instead of OPV (oral polio vaccine) for protection against poliomyelitis. An all IPV-schedule in routine childhood polio vaccination eliminates the - albeit minimal - risk of OPV-associated paralytic poliomyelitis. However, the impact of such a vaccination scheme on the goal to eventually eradicate poliomyelitis on a global level remains debatable. Published studies indicate that vaccine-derived poliovirus may persist in the environment for prolonged periods of time even after completion of a global eradication programme that relies on the near-exclusive use of OPV in the developing countries. Travellers vaccinated with IPV only might become silently infected with vaccine-derived virus, shedding it in large quantities. We therefore plead for a vaccination schedule that includes at least one last dose of OPV to induce strong mucosal immunity.     

Progress toward interruption of wild poliovirus transmission--worldwide, January 2006-May 2007

Progress toward global polio eradication continued during 2006 and the first 5 months of 2007, although the number of countries where wild poliovirus (WPV) transmission has never been interrupted remained at four (Afghanistan, India, Nigeria, and Pakistan). Continuing challenges included intense WPV circulation in northern India during 2006, low vaccination coverage with oral polio vaccine (OPV) during supplemental immunization activities (SIAs) in Nigeria, and security problems preventing access to children during SIAs along the Afghanistan-Pakistan border. Programmatic strategies to address these challenges consisted of large-scale use of type 1 monovalent oral polio vaccine (mOPV1), targeted programs (e.g., cross-border synchronization of polio campaigns) to reach more children through SIAs, and introduction of new laboratory procedures to confirm cases more rapidly. This report summarizes these strategies and overall progress toward global polio eradication.