脊髓灰质炎的流行现状及疫苗免疫策略的研究进展

自1988年世界卫生大会发起全球消灭脊髓灰质炎行动倡议以来,全球脊髓灰质炎发病率已减少了99%以上。如今,全球已进入了后脊灰时代。2013年世界卫生组织制定了《消灭脊髓灰质炎最后阶段战略计划(2013-2018)》,以彻底消灭脊髓灰质炎。由于接种脊髓灰质炎减毒活疫苗(OPV)的人群中有可能会出现罕见的疫苗相关麻痹型脊髓灰质炎(VAPP)病例和疫苗衍生脊髓灰质炎病毒(VDPV)相关病例。因此,彻底消灭脊髓灰质炎的重要途径是研制出有效的疫苗。脊髓灰质炎灭活疫苗(IPV)能避免OPV使用过程中出现的VAPP和VDPV循环(cVDPVs)事件的发生,适用人群较广泛。然而,不同国家的脊髓灰质炎疫苗种类和使用程序不尽相同,本文对脊髓灰质炎流行现状及疫苗免疫策略进展情况进行简述,以期为终结脊髓灰质炎提供理论参考。     

脊髓灰质炎病毒灭活疫苗在控制脊髓灰质炎中的作用

口服脊髓灰质炎（脊灰）减毒活疫苗（Oral Poliomyelitis Attenuate Live Vaccine,OPV）,在控制脊灰进程中发挥了重要作用。全球脊灰发病大幅度下降,目前只有少数几个国家还有脊灰野病毒循环。     

中国在消灭脊髓灰质炎(脊灰)后期使用赛宾株-脊灰灭活疫苗替代口服脊灰减毒活疫苗策略的前瞻性分析

目的 探讨中国在消灭脊髓灰质炎(脊灰)后期的免疫策略.方法 运用循证医学的方法,检索国内外研究资料,调查中国脊灰疫苗生产和使用现状,从免疫策略比较赛宾株-脊灰灭活疫苗(Sabin-Inactivated Poliovirus Vac-cine,slPV)替代口服脊灰减毒活疫苗(Oral Poliomyelitis Live Vaccine,OPV)的可行性,并从免疫程序等方面进行前瞻性综合分析.结果 中国应考虑选择以IPV替代OPV的免疫策略,且国产sIPV即将问世,在政策、技术、疫苗供应和其它保障方面均具备了替代的条件,常规免疫可参照目前OPV免疫程序.结论 中国应进一步加强消灭脊灰后期免疫策略的研究,积极做好sIPV替代OPV的准备工作.     

脊髓灰质炎口服疫苗衍生病毒流行特征及应对策略

自口服脊髓灰质炎减毒活疫苗(Oral Poliovirus Vaccine,OPV)的应用以来,全球脊髓灰质炎感染人数从1988年的350 000例下降到2010年的1 351例,然而,由于OPV使用产生的脊髓灰质炎疫苗衍生病毒(Vaccine-Derived Poliovirus,VDPV)流行,已经成为当代脊灰流行的一个新特点。本文综述了全球近十几年来报道的VDPV病例的发生与流行病学特征,以及为尽早实现全球无脊灰状态目标制定的脊灰病毒消灭策略。     

疫苗衍生脊髓灰质炎病毒相关研究进展

对近些年国内外继续使用口服脊髓灰质炎(脊灰)减毒活疫苗(Oral poliovirus vaccine,OPV)发生的疫苗衍生脊灰病毒(Vaccine-derived poliovirus,VDPV)及其所引起的VDPV循环(Circulating VDPV,cVDPVs)和免疫缺陷疫苗衍生脊灰病毒(Immunodeficient VDPV,iVDPV)病例等相关研究进行了综述,建议我国在实现无脊灰目标后期阶段,应研究制订相应的策略并保证其有效实施。     

灭活脊髓灰质炎病毒疫苗在中国应用的咨询意见调查

目的从扩大免疫规划（Expanded Program on Immunization,EPI）专家认知,来探讨灭活脊髓灰质炎（脊灰）病毒疫苗（Inactivated Poliovirus Vaccine,IPV）在中国应用的相关问题,为制定脊灰疫苗免疫策略提供参考。方法以人口数多和疫苗需求量大为原则,在全国范围内选取7个省（自治区）,对30名EPI专家进行开放式问卷调查。结果50％的调查对象希望在2015年国家能将IPV纳入EPI,与世界卫生组织提出的{2013～2018年消灭脊灰终结战略计划》时间进度表同步,专家们一致认同在保证疫苗质量的前提下,应尽可能地降低疫苗成本,IPV可接受价格中位数为20元／剂（范围5～50元／剂）。实现IPV国产化势在必行,卫生行政等政府部门应尽快明确中国脊灰疫苗免疫策略和使用时间进度表,疾病预防控制中心依据卫生行政部门制定的免疫策略提供技术指导和支持,疫苗生产企业应加快IPV的研发、生产和上市。结论EPI专家一致赞同随着全球消灭脊灰的进程,中国逐步引入IPV是大势所趋。     

口服脊髓灰质炎减毒活疫苗糖丸质量评价

目的分析实施国家批签发前后三价口服脊髓灰质炎减毒活疫苗糖丸(TOPV)的质量及存在问题,评价TOPV的质量。方法通过资料审查和实验室检定,对2002~2004年TOPV检定结果作统计和质量趋势分析。同时将1997~2004年检定的TOPV结果进行了比较。结果共对320批TOPV批记录摘要进行资料审查,其中85批进行实验室检定,结果符合规定。在《中国生物制品规程》(2000年版)及国家批签发实施后,TOPV质量有了明显提高。结论近年来中国TOPV质量稳定。实施国家批签发对TOPV的生产和管理起到规范及监督作用,促进了疫苗质量的提高,但尚存在一些问题。     

脊髓灰质炎减毒活疫苗及其正确应用

应用脊髓灰质炎减毒活疫苗(OPV)免疫适龄儿童,使其获得抵御脊髓灰质炎病毒感染的免疫力,是保护易感人群的最简便、最经济、最有效的方法,也是消灭脊髓灰质炎最为重要的措施。     

脊髓灰质炎灭活疫苗和减毒活疫苗不同序贯免疫程序基础免疫安全性观察

目的 评价脊髓灰质炎灭活疫苗(inactivated polio vaccine,IPV)和减毒活疫苗(oralpolio vaccine,OPV)不同序贯免疫程序基础免疫的安全性.方法 2009至2011年在北京市选择2月龄(60～89 d)婴儿,分为1剂IPV和2剂OPV序贯(I-O-O)、2剂IPV和1剂OPV序贯(I-I-O)、IPV全程(I-I-I)、OPV全程(O-O-O)4个观察组,分别在2、3、4月龄时接种疫苗,收集每次接种后全身和局部不良反应发生情况,计算不良反应发生率.最终入组553名婴儿,中途退出89名,观察1492人次.结果 I-O-O组、I-I-O组、I-I-I组和O-O-O组总不良反应发生率分别为22.9％ (94/410)、18.4％(60/327)、22.0％(78/354)和17.7％(71/401),差异无统计学意义(x2=4.84,P=0.184).第1剂不良反应发生率最高[22.7％(32/141) ～35.3％(54/153)],第2、3剂依次降低.没有与接种疫苗有关的严重不良事件报告.I-O-O组、I-I-O组、I-I-I组和O-O-O组全身不良反应发生率分别为21.5％(88/410)、17.7％(58/327)、20.1％ (71/354)和17.7％(71/401),差异无统计学意义(x2 =2.53,P=0.472).异常哭闹在各组中发生率最高[7.2％(29/401) ～11.3％(37/327)],异常哭闹、嗜睡和易激惹观察到极少数重度不良反应,其他不良反应均为轻、中度反应.I-O-O组、I-I-O组和I-I-I组局部压痛、硬结和红肿发生率分别为2.2％(5/229) ～5.6％(22/393)、0～0.9％(2/229)、0～ 1.0％(4/393),均以轻度为主[0 ～4.1％(5/12t)].结论 IPV全程及IPV/OPV序贯免疫程序与口服三剂OPV-样具有较好的安全性.     

河北省三种脊髓灰质炎疫苗安全性监测分析

目的 比较河北省二价脊髓灰质炎(脊灰)减毒活疫苗(bivalent oral polio attenuated live vaccine, bOPV)、脊灰灭活疫苗(Salk株)(inactivvated poliomyelitis vaccine made from Salk strains, IPV-Salk)和脊灰灭活疫苗(Sabin株)(inactivated poliomyelitis vaccine made from Sabin strains , IPV-Sabin )接种后疑似预防接种异常反应(adverse events following immunization,AEFI)的发生特征,评价脊灰疫苗的安全性。 方法 通过疑似AEFI信息管理系统收集河北省2016年5月1日—2018年4月30日脊灰疫苗接种后AEFI个案,比较分析三种脊灰疫苗接种后AEFI的报告发生情况。 结果 bOPV、IPV-Salk和IPV-Sabin的AEFI报告发生率分别为13.53 / 10万剂、40.50/10万剂和63.70 / 10万剂。bOPV与IPV-Salk、bOPV与IPV-Sabin、IPV-Salk与IPV-Sabin的AEFI报告发生率(χ²= 360.355, P＜0.001,χ²= 360.247, P＜0.001, χ²= 34.895, P＜0.001)和一般反应报告发生率(χ²= 373.009, P＜0.001, χ²= 564.795, P＜0.001, χ²= 35.382,P＜0.001)差异均有统计学意义,由高到低依次为:IPV-Sabin、IPV-Salk和bOPV;异常反应报告发生率(χ²= 3.077,P=0.079, χ²_C= 1.165,P=0.281, χ²_C= 0,P=1)差异均无统计学意义。三种脊灰疫苗的AEFI中均以一般反应为主,年龄主要集中在≤1岁组,主要发生在接种后1 d内。 结论 河北省三种脊灰疫苗总体安全性良好,但仍需加强脊灰疫苗安全性监测。     

Refusal of oral polio vaccine in northwestern Pakistan: A qualitative and quantitative study

Background

Refusal of the oral polio vaccine (OPV) is a difficulty faced by the Polio Eradication Initiative (PEI) in multiple endemic areas, including the Khyber Pakhtunkhwa Province (KPP), Pakistan. In 2007, we investigated community perceptions of the OPV and estimated the prevalence of OPV refusal in three districts in Swat Valley, KPP, a polio-endemic area.

Methods

Qualitative data concerning community perceptions were collected by focus group discussions among lady health workers (LHWs) and mothers with children <1 year old and by key informant interviews with local health managers and officials. Quantitative data collection followed using a questionnaire survey of 200 LHWs and a cluster sampling survey of 210 mothers (per district) with children <1 year old.

Results

The qualitative assessments identified the grounded theory of OPV refusal involving facts known by the residents that are related to the OPV (too frequent OPV campaigns, an OPV boycott in northern Nigeria in 2003 and that birth control is viewed as is against Islam), the local interpretations of these facts (perceptions that OPV contained birth control or pork, that OPV was a foreign/central plot against Muslims, and that the vaccination was against the Hadith and the fate determined by God) and different manifestations of OPV refusal. Among the three districts studied, the proportion of LHWs who encountered OPV refusal ranged from 0 to 33%, whereas among the districts, the proportions of mothers unwilling to give OPV to their children ranged from 0.5 to 5.7%. Refusal of other injectable vaccines was almost equally prevalent for reasons that were very similar.

Conclusions

The PEI needs to reflect local value system in the path to polio eradication in the studied districts in the Swat Valley. The religious and cultural values as well as the interpretation of the international political situation are of particular importance.     

Immunogenicity to poliovirus type 2 following two doses of fractional intradermal inactivated poliovirus vaccine: A novel dose sparing immunization schedule

IntroductionThe polio eradication endgame strategic plan calls for the sequential removal of Sabin poliovirus serotypes from the trivalent oral poliovirus vaccine (tOPV), starting with type 2, and the introduction of ≥1 dose of inactivated poliovirus vaccine (IPV), to maintain an immunity base against poliovirus type 2. The global removal of oral poliovirus type 2 was successfully implemented in May 2016. However, IPV supply constraints has prevented introduction in 21 countries and led to complete stock-out in >20 countries.MethodsWe conducted a literature review and contacted corresponding authors of recent studies with fractional-dose IPV (fIPV), one-fifth of intramuscular dose administered intradermally, to conduct additional type 2 immunogenicity analyses of two fIPV doses compared with one full-dose IPV.ResultsFour studies were identified that assessed immunogenicity of two fIPV doses compared to one full-dose IPV. Two fractional doses are more immunogenic than 1 full-dose, with type 2 seroconversion rates improving between absolute 19–42% (median: 37%, p < 0.001) and relative increase of 53–125% (median: 82%), and antibody titer to type 2 increasing by 2–32-fold (median: 10-fold). Early age of administration and shorter intervals between doses were associated with lower immunogenicity.DiscussionOverall, two fIPV doses are more immunogenic than a single full-dose, associated with significantly increased seroconversion rates and antibody titers. Two fIPV doses together use two-fifth of the vaccine compared to one full-dose IPV. In response to the current IPV shortage, a schedule of two fIPV doses at ages 6 and 14 weeks has been endorsed by technical oversight committees and has been introduced in some affected countries.     

Persistence of protective anti-poliovirus antibody levels in 4-year-old children previously primed with Picovax®, a trivalent,aluminium-adjuvanted reduced dose inactivated polio vaccine

BackgroundTo meet the demand for effective and affordable inactivated polio vaccines (IPVs), a reduced dose, aluminium hydroxide (Al(OH)₃)-adjuvanted IPV vaccine was developed (IPV-Al, Picovax®) and evaluated in clinical trials. The present trial is an extension of two previous trials (a primary and a booster trial). The aim was to evaluate the persistence of seroprotective antibodies (poliovirus type-specific antibody titre ≥ 8) in 4-year-old children who previously received IPV–Al as primary and booster vaccine doses and to determine the potential booster response and safety profile of an additional dose of IPV-Al.MethodsChildren participating in the two previous trials were invited to receive one additional dose of IPV-Al at 4 years of age (2.5 years after the booster dose) and to have their blood samples collected to measure the pre- and post-vaccination antibody titres. Systemic adverse events (AEs) and local reactogenicity were recorded.ResultsAt study entry, the seroprotection rates were 89.2%, 100% and 91.1% against poliovirus type 1, 2 and 3, respectively. The additional vaccination with IPV-Al boosted the level of poliovirus type 1, 2 and 3 antibodies to above the seroprotection threshold for all but one subject, i.e., 99.4% for type 1 and 100% for types 2 and 3. The additional dose induced a robust booster response of a 26.3-, 13.9- and 30.9-fold increase in titre for poliovirus types 1, 2 and 3, respectively. The vaccine was well tolerated, with only mild and transient AEs reported.ConclusionsThe present trial demonstrated that the primary vaccination with an aluminium-adjuvanted reduced dose IPV induced a persistent immune memory as evidenced by the robust anamnestic response when the subjects were re-exposed to the antigen 2.5 years after the last dose. Thus, the IPV-Al is an efficient and safe addition to increase the availability of inactivated polio vaccines globally. (ClinicalTrials.gov reg no. NCT04448132).     

实验室检测脊髓灰质炎疫苗滴度应注意的问题

Ｈｅｐ－２细胞是脊髓灰质炎（脊灰）病毒的敏感细胞之一，其敏感性受多种因素制约，本文以培养Ｈｅｐ－２细胞是否使用乳蛋白水解物及小牛血清的质量差异对脊灰糖丸疫苗滴度的影响进行了分析。结果表明：乳蛋白水解物的使用可使脊灰三价糖丸疫苗总滴度平均提高０．３６ＬｏｇＣＣＩＤ５０／粒，显著高于未使用乳蛋白水解物培养的Ｈｅｐ－２细胞。另外，小中血清的影响不容忽视，本文发现有些进口小牛血清对病毒的生长产生非特异性抑制，对脊灰病毒的抑制滴度可达１．９ＬｏｇＣＣＩＤ５０／ｍｌ以上。这提示我们。组织培养试剂的更换应格外慎重，实验室标准体系的建立也是非常必要的。     

口服脊髓灰质炎减毒活疫苗相关病例研究现状

“脊髓灰质炎”（简称脊灰）是由脊灰病毒引起的一种急性肠道传染病,疫苗免疫预防是控制乃至消灭脊灰最重要的策略。世界卫生组织（WHO）推荐用于全球消灭脊灰的主导疫苗是口服脊髓灰质炎减毒活疫苗（OPV）。OPV在安全性方面存在一定问题：服用OPV可能引起麻痹型病例,即疫苗相关病例（vaccine-associated paralytic poliomyelitis,VAPP）。目前除了非洲以外,各大洲均有关于VAPP发生的报道。20世纪90年代以来,我国有近20个省、市、自治区报告发生了VAPP病例。WHO1970-1979年对6个国家的VAPP进行研究,发病率为0.07/100万,其中55%为Ⅲ型相关病例,38%为Ⅱ型相关病例,Ⅰ型的仅为7%,服苗病例主要由Ⅲ型疫苗病毒引起,接触病例中Ⅱ型疫苗病毒多见。VAPP发病机制主要有病毒基因突变、病毒基因重组、免疫缺陷等。消灭脊髓灰质炎以后是否应停止脊灰疫苗免疫并以此作为全球消灭脊灰的最终目标是全球专家正在讨论的问题。     

中国2003年脊髓灰质炎实验室网络的运转与监测

2 0 0 3年 ,中国 31个省 (自治区、直辖市 ,下同 )疾病预防控制中心 (CDC)脊髓灰质炎 (脊灰 )实验室 ,从 5 0 1 4例急性弛缓性麻痹 (AFP)病例中收集了 9987份粪便标本 ,所有粪便标本用L2 0B、RD细胞同时进行肠道病毒分离。从 373例AFP病例粪便标本中分离到脊灰病毒 (PV) ,分离率为 7 4%。然后对所有病毒做了血清定型 ,其中Ⅰ型5 5例 ,Ⅱ型 1 32例 ,Ⅲ型 70例 ,混合型 74例 ,PV与非脊灰肠道病毒 (NPEV)混合 1 6例。从 4 79例AFP病例粪便标本中分离到NPEV ,分离率为 9 6 %。中国CDC病毒病预防控制所国家脊灰实验室共收到送检的 4 75株PV标本 ,其中 373株来源于AFP病例 ,1 0 2株从AFP病例接触者、流动人口、非AFP病例、健康人群等分离到。对送检的 4 75株进行了血清型中和试验复核 ,并使用酶联免疫吸附试验 (ELISA)和聚合酶链反应 限制性内切酶片段长度多态性分析 (PCR RFLP)两种方法进行型内鉴定。血清型中和试验复核和PCR RFLP鉴定结果显示 :4 75株中 ,PVⅠ型疫苗株 80株 ,Ⅱ型疫苗株 1 4 6株 ,Ⅲ型疫苗株 1 0 5株 ,混合型疫苗株 98株 ,PV NPEV1 7株 ,疫苗Ⅰ、Ⅱ、Ⅲ型变异株分别为 1 0、1 0、9株。将PV混合株进行单型分离后 ,所有单型毒株共 5 96株 ,经ELISA试验鉴定 ,其中疫苗类似株 (SL) 5 73株 ,占     

Evaluating cessation of the type 2 oral polio vaccine by modeling pre- and post-cessation detection rates

The globally synchronized removal of the attenuated Sabin type 2 strain from the oral polio vaccine (OPV) in April 2016 marked a major change in polio vaccination policy. This change will provide a significant reduction in the burden of vaccine-associated paralytic polio (VAPP), but may increase the risk of circulating vaccine-derived poliovirus (cVDPV2) outbreaks during the transition period. This risk can be monitored by tracking the disappearance of Sabin-like type 2 (SL2) using data from the polio surveillance system. We studied SL2 prevalence in 17 countries in Africa and Asia, from 2010 to 2016 using acute flaccid paralysis surveillance data. We modeled the peak and decay of SL2 prevalence following mass vaccination events using a beta-binomial model for the detection rate, and a Ricker function for the temporal dependence. We found type 2 circulated the longest of all serotypes after a vaccination campaign, but that SL2 prevalence returned to baseline levels in approximately 50 days. Post-cessation model predictions identified 19 anomalous SL2 detections outside of model predictions in Afghanistan, India, Nigeria, Pakistan, and western Africa. Our models established benchmarks for the duration of SL2 detection after OPV2 cessation. As predicted, SL2 detection rates have plummeted, except in Nigeria where OPV2 use continued for some time in response to recent cVDPV2 detections. However, the anomalous SL2 detections suggest specific areas that merit enhanced monitoring for signs of cVDPV2 outbreaks.     

Lower immunity to poliomyelitis viruses in Australian young adults not eligible for inactivated polio vaccine

There are limited long-term data on seroprevalence of neutralising antibody (nAb) to the three poliovirus serotypes following the switch from oral polio vaccine (OPV) to inactivated polio vaccine (IPV). In Australia, combination vaccines containing IPV replaced OPV in late 2005. Using serum and plasma specimens collected during 2012 and 2013, we compared prevalence of nAb to poliovirus type 1 (PV1), type 2 (PV2) and type 3 (PV3) in birth cohorts with differing IPV and OPV eligibility from an Australian population-based sample. In the total sample of 1673 persons aged 12 months to 99 years, 85% had nAb against PV1, 83% PV2 and 67% PV3. In the cohort 12 to <18 years (eligible for 4 OPV doses, last dose 8–14 years prior), a significantly lower proportion had nAb than in the 7 to <12 year cohort (eligible for 3 OPV doses and an IPV booster, last dose 3–8 years prior) for all poliovirus types: [PV1: 87.1% vs. 95.9% (P = 0.01), PV2: 80.4% vs. 92.9% (P = 0.003) and PV3: 38.1% vs. 84.0% (P < 0.0001)]. These data suggest individual-level immunity may be better maintained when an OPV primary schedule is boosted by IPV, and support inclusion of an IPV booster in travel recommendations for young adults who previously received only OPV.