关键词： Poliovirus   Vaccine   Oral poliovirus vaccine   Vaccine effectiveness   Afghanistan  

摘要： Background: Afghanistan is one of two countries with endemic wild poliovirus type 1 (WPV1). The oral poliovirus vaccine (OPV) is the predominant vaccine used for polio eradication. Although OPV has been administered in routine childhood immunization and during frequent supplementary immunization activities, WPV1 continues to circulate in Afghanistan and case incidence has been increasing since 2017. We estimated the effectiveness of OPV in Afghanistan during 2010-2020. Methods: We conducted a matched case-control analysis using acute flaccid paralysis (AFP) surveillance data from 29,370 children < 15 years with AFP onset between January 1, 2010 and December 31, 2020. We matched children with confirmed WPV1 (cases) with children with non-polio AFP (controls) by age at onset of paralysis (+/-3 months), date of onset of paralysis (+/-3 months), and province of residence, and compared their reported OPV vaccination history to estimate the effectiveness of OPV in preventing paralysis by WPV1 using conditional logistic regression. To account for changes in OPV formulations provided over the analysis period, we stratified the analysis based on dates of the global switch from trivalent OPV (tOPV) to bivalent OPV (bOPV) in April 2016. Results: Between January 1, 2010 and December 31, 2020, there were 329 WPV1 cases in Afghanistan. The per-dose estimated effectiveness of OPV against WPV1 was 19% (95% CI: 15%-22%) and of > 7 doses was 94% (95% CI: 90%-97%). Before the global switch from tOPV to bOPV, the per-dose estimated effectiveness of OPV was 14% (95% CI: 11%-18%) and of > 7 doses was 92% (95% CI: 85%-96%). After the switch, the per-dose estimated effectiveness of OPV against WPV1 was 32% (24%-39%) and of > 7 doses was 96% (95% CI: 90%-99%). Discussion: OPV is highly effective in preventing paralysis by WPV1;these results indicate that continued WPV1 transmission in Afghanistan is due to failure to vaccinate, not failure of the vaccine. Although difficult to implement in

关键词： 脊髓灰质炎病毒   甲醛   Hep-2细胞   病毒灭活  

摘要： 目的验证4%甲醛溶液使Sabin株Ⅰ、Ⅱ、Ⅲ型脊髓灰质炎(脊灰)病毒达到预期灭活效果所需要的时间。方法用4%甲醛溶液对15批Sabin株Ⅰ、Ⅱ、Ⅲ型脊灰病毒在(36.5±1.0)℃环境进行灭活,同时以15批未加入4%甲醛溶液的病毒纯化液作为对照组,按照企业注册标准采用微量细胞病变法测定病毒滴度。为了消除4%甲醛溶液对Hep-2细胞的影响,取4%甲醛溶液接种Hep-2细胞作为实验组,同时设置Hep-2细胞为对照组,每天观察对比两组细胞形态。对同一个Hep-2细胞悬液的总细胞数和活细胞数采用传统手工计数和全自动细胞计数仪计数,并比较分析结果。结果实验组随着灭活时间的延长病毒滴度呈下降趋势,灭活第4天起,3个型别样品均检测不到病毒滴度;对照组病毒滴度在每毫升9.1~10.6 lg半数细胞培养物感染量范围内,符合企业注册标准的要求。4%甲醛溶液对Hep-2细胞生长有抑制作用,在培养观察到第3天时细胞全部失去活力死亡;对照组细胞形态良好呈多边形长成致密单层,活细胞组t值为18.098,总细胞组t值为4.005,P值均<0.05,差异有统计学意义。结论脊髓灰质炎病毒在第4天能被彻底灭活,在进行此实验时应先消除甲醛对细胞培养的影响,避免结果出现假病变现象,确保结果的准确性;应用全自动细胞计数能提高计数结果的精确度。

关键词： 脊髓灰质炎   脊髓灰质炎减毒活疫苗   中和抗体   免疫水平  

摘要： 目的持续监测12岁以下儿童脊髓灰质炎病毒(poliovirus,PV)中和抗体(neutralizing antibody,NA)水平,确定疫苗转换对目标儿童NA水平的影响。方法采用分层整群和完全随机抽样方法,从福建省9个设区市抽取<12岁儿童,采集血标本,应用微量中和试验进行NA测定。结果调查<12岁儿童2134名,PVⅠ型和PVⅢ型NA阳性率分别为98.64%和95.83%;几何平均滴度(geometric mean titer,GMT)分别为1∶259.35和1∶105.14,随着年龄的增长而呈下降趋势。与三价减毒活疫苗(trivalent oral poliovirus vaccine,tOPV)相比,二价减毒活疫苗(bivalent oral poliovirus vaccine,bOPV)和灭活疫苗(inactivated poliovirus vaccine,IPV)能分别诱导产生PVⅠ型和PVⅢ型的GMT值更高。在182名<5岁儿童中,PVⅠ型、Ⅱ型和Ⅲ型NA阳性率分别为97.25%、76.37%和92.86%,3型间差异有统计学意义(χ^(2)=44.44,P=0.000),PVⅡ型显著低于PVⅠ型和PVⅢ型(PVⅡ型VS PVⅠ型:χ^(2)=34.65,P=0.000;PVⅡ型VS PVⅢ型:χ^(2)=18.99,P=0.000);3型GMT分别为1∶368.96、1∶23.06和1∶183.10,差别有统计学意义(F=156.54,P=0.000),其中以PVⅠ型为最高,PVⅢ型次之,PVⅡ型最低(两两比较P值均为0.000)。一般线性模型分析显示,最后一剂脊灰疫苗接种时间距调查时间间隔对PVⅠ型和PVⅢ型GMT值有影响,不同接种模式仅对PVⅠ型GMT值有影响,但年龄可能是混杂因素;而对PVⅡ型均无影响。结论疫苗转换后儿童PVⅠ型和Ⅲ型NA水平仍维持在较高水平,但<5岁儿童PVⅡ型抗体水平则相对较低,需加强监测。

关键词： 脊髓灰质炎病毒   病毒样颗粒   昆虫细胞   重组杆状病毒  

摘要： 目的构建共表达P1和3CD的重组杆状病毒,利用昆虫细胞重组表达2型脊髓灰质炎病毒(poliovirus type 2,PV2)的病毒样颗粒(virus-like particle,VLP),制备PV2-VLP进行初步免疫原性研究。方法基于粉纹夜蛾细胞(High 5)密码子偏好性,将PV2的P1基因和3CD基因进行序列优化,并对P1基因进行稳定性突变,构建突变型rBac-PV2-P1s-3CD和野生型rBac-PV2-P1-3CD杆状病毒。Western blot分别检测目的蛋白表达量,离子交换层析纯化PV2-VLP,透射电镜观察VLP高级结构确定组装效率。免疫大鼠评估免疫原性。结果成功构建了可稳定表达P1s蛋白和3CD蛋白的重组杆状病毒。Western blot结果表明热稳定性突变后VLP产量相比野生型有所提高。电镜观察发现直径约30 nm的三维结构,表明VLP成功组装。动物实验结果表明,重组制备的PV2-VLP具有免疫原性,且能有效刺激产生中和抗体。结论用昆虫细胞-杆状病毒表达系统可成功制备有效的VLP类疫苗,为PV-VLP疫苗的研制提供参考。

关键词： 季铵盐   脊髓灰质炎病毒   低温   灭活效果   毒性  

摘要： 目的观察一种复合季铵盐低温消毒液对病毒的灭活效果及其毒性。方法采用载体定量杀灭试验和动物试验方法,对低温下病毒灭活效果及毒性进行观察。结果用含量为5000 mg/L的该复合季铵盐消毒液,在20℃条件下作用5.0 min和-18℃条件下作用20 min,对载体上脊髓灰质炎病毒的灭活对数值均≥4.00,在-18℃冷库环境下作用20 min,对载体上脊髓灰质炎病毒的灭活对数值均≥4.00。该季铵盐消毒液急性经口毒性LD_(50)值>5000 mg/(kg·bw),一次作用于完整皮肤无刺激性,对小鼠骨髓嗜多染红细胞微核形成无影响。结论该复合季铵盐毒液在-18℃条件下,对病毒具有很好的杀灭效果,属于实际无毒物质。

关键词： 脊髓灰质炎灭活疫苗   疑似预防接种异常反应   安全性  

摘要： 目的分析2018—2020年陕西省Sabin株脊髓灰质炎灭活疫苗[inactivated poliomyelitis vaccine prepared from Sabin strain(Vero cells),sIPV]疑似预防接种异常反应(adverse event following immunization,AEFI)的发生情况。方法通过AEFI监测信息管理系统收集陕西省2018年1月1日—2020年5月6日sIPV监测数据,采用描述性流行病学方法进行分析。结果陕西省2018年1月1日—2020年5月6日共报告sIPV的AEFI病例141例,报告发生率为34.24/10万,其中一般反应报告发生率为32.29/10万,异常反应报告发生率为1.46/10万。一般反应以发热(占比42.68%)、婴儿哭闹(占比18.41%)、疫苗接种部位肿胀(占比12.97%)为主,异常反应以过敏性皮疹(占比42.86%)为主。无严重AEFI病例报告,AEFI病例总体转归情况良好。结论 sIPV具有良好的安全性,AEFI以一般反应为主。

关键词： 疫苗衍生病毒   脊髓灰质炎   免疫缺陷者Ⅲ型疫苗衍生脊髓灰质炎病毒   急性弛缓性麻痹   查漏补种  

摘要： 目的探索疫苗衍生脊髓灰质炎病毒(VDPV)病例管控措施及治疗方法,为应急处置方案的制定提供依据。方法对VDPV病例进行个案调查,采集病例及其父母血液标本进行免疫功能测定和基因检测,并定期采集病例粪便标本分离病毒,对病例所在地和医疗机构开展AFP病例主动搜索,进行儿童脊灰疫苗接种率调查,开展脊灰疫苗查漏补种和应急免疫,对密切接触者和周围健康儿童进行粪便标本带毒率调查和脊灰抗体阳转率检测。结果病例多次进行免疫功能测定,结果显示体内免疫球蛋白含量低于正常值,临床诊断为原发性免疫缺陷综合征,最终分类诊断为免疫缺陷者Ⅲ型疫苗衍生脊髓灰质炎病毒(iVDPV)病例。共计采集患儿粪便标本108份,其中69份标本检测到脊髓灰质炎病毒,病毒核苷酸最大变异数为37个。丙种球蛋白治疗持续24个月,未能阻断VDPV在肠道内的复制。当地的儿童常规免疫接种率较高,脊灰抗体滴度较高。同时AFP监测系统运转良好,监测灵敏度较高。结论在采取排泄物消毒、脊灰疫苗查漏补种、AFP主动搜索等措施后,该病毒未在当地造成循环。职能部门果断实施突发公共卫生事件Ⅵ级应急响应,开展查漏补种和应急免疫等活动,整个应急处置过程严谨规范,快速有效。当前应保持高水平的脊灰疫苗接种率,保持监测系统高度灵敏性,维持无脊灰状态。同时随着全球消灭脊灰的进展,应适时修订免疫策略。

关键词： 麻痹型脊髓灰质炎病例(VAPP)   脊髓灰质炎减毒活疫苗(OPV)   疫苗相关   预防接种  

摘要： 目的分析脊灰疫苗免疫策略调整前后泉州市疫苗相关麻痹型脊髓灰质炎病例(VAPP)的发生与流行特征,为消灭脊灰防控提供依据。方法对泉州市2006—2020年报告的VAPP病例进行描述性分析。结果 2006—2020年共报告诊断VAPP病例8例,均为首剂接种脊髓灰质炎减毒活疫苗(OPV)后发生,免疫儿童VAPP发生率为3.98/100万人,服用OPV者VAPP发生率为0.83/100万剂次,首剂服OPV者VAPP发生率5.83/100万剂次。首剂引入脊灰灭活疫苗(IPV)后,2017—2020年VAPP病例发生数为0。8例VAPP均为男性,为2~5月龄儿童;疫苗接种时间距发热平均间隔16.9 d,距发生麻痹平均间隔22.0 d,病例均残留麻痹;2例有肛周脓肿史;57.1%(4/7)病例粪便标本中分离出脊灰病毒疫苗株,其中2例分离到Ⅲ型疫苗株,2例分离到Ⅰ型疫苗株。结论 VAPP病例主要集中在小月龄、首剂OPV接种婴幼儿。2017年以来首剂均接种含3个血清型的脊灰灭活疫苗(IPV)后未再发现VAPP病例,显示脊灰疫苗策略转换成效。

关键词： 生活污水监测   脊灰病毒   疫苗相似株  

摘要： 目的持续监测2019年生活污水中的脊髓灰质炎病毒(poliovirus,PV),了解脊灰病毒在外环境中的流行变化趋势,为维持无脊灰状态提供实验室环境监测数据支持。方法选择南昌市某区污水处理厂作为长期固定监测点,每月在污水处理厂入水口采集1 L污水作为样本。膜浓缩后在L20B、RD、Hep-2三种细胞上进行病毒分离培养,对阳性分离物进行VP1全长基因的测序分析。结果共分离出脊灰病毒25株,分离率为91.67%(11/12),包括PVⅠ型3株,PVⅢ型22株,PVⅡ型0株。3株PVⅠ型毒株均为疫苗相似株,在全基因组的2749位点处均由腺嘌呤A突变为鸟嘌呤G,导致异亮氨酸突变成甲硫氨酸;2株PVⅢ(JX2019JHH037L、JX2019JHH042R)在2636位点处发生了由鸟嘌呤G突变为腺嘌呤A变异,导致了亲水氨基酸丙氨酸替代了疏水氨基酸苏氨酸。结论在生活污水监测中分离到的脊灰病毒株均为疫苗株和疫苗相似株,未发现脊灰野毒株、脊灰疫苗衍生株及PVⅡ毒株。因此为维持无脊灰状态,需要持续对污水等外环境标本加强监测。

关键词： Poliovirus   Inactivated poliovirus vaccine   Immunization schedule  

摘要： Background: After global oral poliovirus vaccine (OPV) cessation, the Strategic Advisory Group of Experts on Immunization (SAGE) currently recommends a two-dose schedule of inactivated poliovirus vaccine (IPV) beginning >14-weeks of age to achieve at least 90% immune response. We aimed to compare the immunogenicity of three different two-dose IPV schedules started before or at 14-weeks of age. Methods: We conducted a randomized, controlled, open-label, inequality trial at two sites in Dhaka, Bangladesh. Healthy infants at 6-weeks of age were randomized into one of five arms to receive two dose IPV schedules at different ages with and without OPV. The three IPV-only arms are presented: Arm C received IPV at 14-weeks and 9-months;Arm D received IPV at 6-weeks and 9-months;and Arm E received IPV at 6 and 14-weeks. The primary outcome was immune response defined as seroconversion from seronegative (<1:8) to seropositive (>1:8) after vaccination, or a four-fold rise in antibody titers and median reciprocal antibody titers to all three poliovirus types measured at 10-months of age. Findings: Of the 987 children randomized to Arms C, D, and E, 936 were included in the intention-to-treat analysis. At 10-months, participants in Arm C (IPV at 14-weeks and 9-months) had >99% cumulative immune response to all three poliovirus types which was significantly higher than the 77-81% observed in Arm E (IPV at 6 and 14-weeks). Participants in Arm D (IPV at 6-weeks and 9-months) had cumulative immune responses of 98-99% which was significantly higher than that of Arm E (p value < 0.0001) but not different from Arm C. Interpretation: Results support current SAGE recommendations for IPV following OPV cessation and provide evidence that the schedule of two full IPV doses could begin as early as 6-weeks. (c) 2021 Published by Elsevier Ltd.