A nation-wide case surveillance was conducted in China since 1995 for the objective of identifying acute flaccid paralysis(AFP)in children so that potential wild polioviruses and vaccine-derived poliovirus(VDPV)could ...A nation-wide case surveillance was conducted in China since 1995 for the objective of identifying acute flaccid paralysis(AFP)in children so that potential wild polioviruses and vaccine-derived poliovirus(VDPV)could be identified on time.Two outbreaks associated with type I circulating VDPVs,eight native independent type I ambiguous VDPVs(aVDPV),and one imported aVDPV were identified during the AFP case surveillance in China from 1995 to 2019.The VP1 coding region of the Chinese type I VDPVs differed from the polio vaccine strain by 1.00%–3.75%(9–34 substitutions in 906 nucleotides).Most of the Chinese type I VDPV strains shared 4 amino acid substitutions in the neutralizing antigenic(NAg)sites:3 located at the BC loop,which formed the NAg site 1,and another at NAg site 3a.All of the Chinese type I VDPVs identified during the AFP case surveillance were young VDPVs,which indicated a limited viral replication resulted from the administration of the initiating oral polio vaccine(OPV)dose.VDPVs can emerge and spread in isolated communities with immunity gaps and the circulation ceases following a mass immunization with OPV.As such,high-quality surveillance permitted very early detection and response and it played a key role in stalling the widespread circulation of the emergent cVDPV strains in China.展开更多
Background:Vaccine-derived poliovirus(VDPV)is a potential threat to polio eradication because they can reintroduce into the general population and cause paralytic polio outbreaks,a phenomenon that has recently emerged...Background:Vaccine-derived poliovirus(VDPV)is a potential threat to polio eradication because they can reintroduce into the general population and cause paralytic polio outbreaks,a phenomenon that has recently emerged as a prominent public health concern at the end of global polio eradication.This study aimed to describe the epidemiology and genetic characteristics of the frst VDPV identifed from a patient with acute faccid paralysis(AFP),with four doses of inactivated polio vaccine immunization in Henan Province,China in 2017.Methods:The patient was diagnosed with type 3 VDPV.Subsequently,a series of epidemiological approaches was implemented,including a retrospective search of AFP cases,rate of vaccination assessment,study of contacts,and supplementary immunization activities.Fecal samples were collected,viral isolation was performed,and the viral isolates were characterized using full-length genomic sequencing and bioinformatic analysis.Results:Phylogenetic analysis showed that the viral isolates from the patient were diferent from other reported genetic clusters of type 3 VDPV worldwide.They were identifed as a Sabin 3/Sabin 1 recombinant VDPV with a crossover site in the P2 region.Nucleotide substitutions,including U→C(472)and C→U(2493),have been identifed,both of which are frequently observed as reversion mutations in neurovirulent type 3 poliovirus.A unique aspect of this case is that the patient had been vaccinated with four doses of inactive polio vaccine,and the serum neutralizing antibody for Sabin types 1 and 3 were 1∶16 and 1∶512,respectively.Thus,the patient was speculated to have been infected with type 3 VDPV,and the virus continued to replicate and be excreted for at least 41 d.Conclusions:The existence of this kind of virus in human population is a serious risk and poses a severe challenge in maintaining a polio-free status in China.To the best of our knowledge,this is the frst report of VDPV identifed in the Henan province of China.Our results highlight the importance of maintaining a high-level vaccination rate and highly sensitive AFP case surveillance system in intercepting VDPV transmission.展开更多
An error in a previous publication in the calculation of the average age at first infection for the model is corrected here.The average age at first infection for the effective contact rates used to generate the data ...An error in a previous publication in the calculation of the average age at first infection for the model is corrected here.The average age at first infection for the effective contact rates used to generate the data ranges from 1.2 to 3.3 years of age instead of 3e5 years of age as advertised in the previous version of the paper.This change has an effect on the force of infection generated by this model.In this corrigendum,we demonstrate the correct method to calculate the average age at first infection for the model.We compare the forces of infection that correspond to these ages in our model with the forces of infection in other endemic populations.We show that the modified age range corresponds to forces of infection which are higher than those that are known to exist in historical studies of polioendemic regions.Thus,the results in the paper have limited applicability to real-world endemic situations.展开更多
Background:Small populations that have been isolated by conflict make vaccination and surveillance difficult,threatening polio eradication.Silent circulation is caused by asymptomatic infections.It is currently not cl...Background:Small populations that have been isolated by conflict make vaccination and surveillance difficult,threatening polio eradication.Silent circulation is caused by asymptomatic infections.It is currently not clear whether the dynamics of waning immunity also influence the risk of silent circulation in the absence of vaccination.Such circulation can,nevertheless,be present following a declaration of elimination as a result of inadequate acute flaccid paralysis surveillance(AFPS)or environmental surveillance(ES).Methods:We have constructed a stochastic model to understand how stochastic effects alter the ability of small populations to sustain virus circulation in the absence of vaccination.We analyzed how the stochastic process determinants of the duration of silent circulation that could have been detected by ES were affected by R0,waning dynamics,population size,and AFPS sensitivity in a discrete individual stochastic model with homogeneous contagiousness and random mixing.We measured the duration of silent circulation both by the interval between detected acute flaccid paralysis(AFP)cases and the duration of circulation until elimination.Results:As R0 increased and population size increased,the interval between detected AFP cases and the duration of circulation until elimination increased.As AFPS detection rates decreased,the interval between detected AFP cases increased.There was up to a 22%chance of silent circulation lasting for more than 3 years with 100%AFP detection.The duration of silent circulation was not affected by the waning immunity dynamics.Conclusion:We demonstrated that small populations have the potential to sustain prolonged silent circulation.Surveillance in these areas should be intensified before declaring elimination.To further validate these conclusions,it is necessary to realistically relax the simplifying assumptions about mixing and waning.展开更多
目的分析中国（未包括香港、澳门特别行政区和台湾地区，下同）实现无脊髓灰质炎（脊灰）目标后，疫苗衍生脊灰病毒（Vaccine—derived Poliovirus，VDPV）的发生情况。方法分析31个省（自治区、直辖市，下同）报告的急性弛缓性麻痹（Ac...目的分析中国（未包括香港、澳门特别行政区和台湾地区，下同）实现无脊髓灰质炎（脊灰）目标后，疫苗衍生脊灰病毒（Vaccine—derived Poliovirus，VDPV）的发生情况。方法分析31个省（自治区、直辖市，下同）报告的急性弛缓性麻痹（Acute Flaccid Paralysis，AFP）病例数据库、中国疾病预防控制中心（Center for Disease Control and Prevention，CDC）病毒病预防控制所国家脊灰实验室，对脊灰病毒阳性分离物的基因测序结果，各级CDC对VDPV及病例的调查和处置报告。结果2001～2013年，中国AFP病例监测系统从37名儿童粪便标本中分离到VDPV，来源于12个省，其中AFP病例22例，AFP病例接触者13人，健康儿童2人。其中2004年贵州省2例Ⅰ型（Type1）VDPV（VDPVI）病例形成循环（Circulating）（cVDPVⅠ），2011～2012年四川省Ⅱ型（Type2）疫苗高变异脊灰病毒（Vaccine—hypervariable Poliovirus，VHPVⅡ）病例／VDPVⅡ病例形成cVHPVⅡ／cVDPVⅡ。结论VDPV可在健康儿童粪便中检出，也能导致儿童麻痹。其发生有疫苗因素，也有受种者因素和疫苗使用因素。口服脊灰减毒活疫苗（Oral Poliomyelitis Attenuated Live Vaccine，OPV）接种率低，是造成发生cVDPV的原因。只有达到人群OPV的高免疫覆盖率，通过高质量的AFP病例监测系统及时发现病例，采取有效措施及时控制疫情，才能阻断病毒的传播。展开更多
目的评价2019年6月四川省凉山州Ⅱ型疫苗衍生脊髓灰质炎(脊灰)病毒循环(Circulating vaccine-derived poliovirus type II,cVDPV2)相关儿童脊灰病毒(Poliovirus,PV)中和抗体水平。方法在发生cVDPV2的雷波县田坝村选取所有1-5岁儿童,在...目的评价2019年6月四川省凉山州Ⅱ型疫苗衍生脊髓灰质炎(脊灰)病毒循环(Circulating vaccine-derived poliovirus type II,cVDPV2)相关儿童脊灰病毒(Poliovirus,PV)中和抗体水平。方法在发生cVDPV2的雷波县田坝村选取所有1-5岁儿童,在雷波县其他地区和凉山州其他6个县采用便利抽样法抽取1-5岁儿童,采集血清标本,应用微量中和试验检测PVⅠ、PVⅡ、PVⅢ和/或cVDPV2中和抗体,分析抗体阳性率和几何平均滴度(Geometric mean titer,GMT)。结果在凉山州7个县(不包括田坝村)697名儿童中,PVⅠ、PVⅡ、PVⅢ中和抗体阳性率分别为90.8%、78.5%、85.5%,GMT分别为1∶85.1、1∶25.2、1∶37.1;各型PV抗体水平均随年龄增长而先下降再上升,且在7个县之间具有显著性差异。在雷波县田坝村52名儿童中,PVⅠ、PVⅡ、PVⅢ、cVDPV2中和抗体阳性率分别为44.2%、34.6%、38.5%、84.6%,GMT分别为1∶9.5、1∶5.1、1∶8.2、1∶89.9;在雷波县其他地区100名儿童中,相应中和抗体阳性率为分别为88.0%、75.0%、80.0%、79.0%,GMT分别为1∶69.4、1∶12.3、1∶32.5、1∶18.0。结论本起cVDPV2发生地区的儿童存在脊灰免疫空白,cVDPV2循环时间较久且传播广泛,凉山州1-5岁儿童脊灰免疫水平较低,需加强儿童脊灰预防接种工作。展开更多
基金This study was supported by the National Science and Technology Major Project of China(Project Nos.2018ZX10711001,2017ZX10104001,and 2018ZX10713002).
文摘A nation-wide case surveillance was conducted in China since 1995 for the objective of identifying acute flaccid paralysis(AFP)in children so that potential wild polioviruses and vaccine-derived poliovirus(VDPV)could be identified on time.Two outbreaks associated with type I circulating VDPVs,eight native independent type I ambiguous VDPVs(aVDPV),and one imported aVDPV were identified during the AFP case surveillance in China from 1995 to 2019.The VP1 coding region of the Chinese type I VDPVs differed from the polio vaccine strain by 1.00%–3.75%(9–34 substitutions in 906 nucleotides).Most of the Chinese type I VDPV strains shared 4 amino acid substitutions in the neutralizing antigenic(NAg)sites:3 located at the BC loop,which formed the NAg site 1,and another at NAg site 3a.All of the Chinese type I VDPVs identified during the AFP case surveillance were young VDPVs,which indicated a limited viral replication resulted from the administration of the initiating oral polio vaccine(OPV)dose.VDPVs can emerge and spread in isolated communities with immunity gaps and the circulation ceases following a mass immunization with OPV.As such,high-quality surveillance permitted very early detection and response and it played a key role in stalling the widespread circulation of the emergent cVDPV strains in China.
文摘Background:Vaccine-derived poliovirus(VDPV)is a potential threat to polio eradication because they can reintroduce into the general population and cause paralytic polio outbreaks,a phenomenon that has recently emerged as a prominent public health concern at the end of global polio eradication.This study aimed to describe the epidemiology and genetic characteristics of the frst VDPV identifed from a patient with acute faccid paralysis(AFP),with four doses of inactivated polio vaccine immunization in Henan Province,China in 2017.Methods:The patient was diagnosed with type 3 VDPV.Subsequently,a series of epidemiological approaches was implemented,including a retrospective search of AFP cases,rate of vaccination assessment,study of contacts,and supplementary immunization activities.Fecal samples were collected,viral isolation was performed,and the viral isolates were characterized using full-length genomic sequencing and bioinformatic analysis.Results:Phylogenetic analysis showed that the viral isolates from the patient were diferent from other reported genetic clusters of type 3 VDPV worldwide.They were identifed as a Sabin 3/Sabin 1 recombinant VDPV with a crossover site in the P2 region.Nucleotide substitutions,including U→C(472)and C→U(2493),have been identifed,both of which are frequently observed as reversion mutations in neurovirulent type 3 poliovirus.A unique aspect of this case is that the patient had been vaccinated with four doses of inactive polio vaccine,and the serum neutralizing antibody for Sabin types 1 and 3 were 1∶16 and 1∶512,respectively.Thus,the patient was speculated to have been infected with type 3 VDPV,and the virus continued to replicate and be excreted for at least 41 d.Conclusions:The existence of this kind of virus in human population is a serious risk and poses a severe challenge in maintaining a polio-free status in China.To the best of our knowledge,this is the frst report of VDPV identifed in the Henan province of China.Our results highlight the importance of maintaining a high-level vaccination rate and highly sensitive AFP case surveillance system in intercepting VDPV transmission.
文摘An error in a previous publication in the calculation of the average age at first infection for the model is corrected here.The average age at first infection for the effective contact rates used to generate the data ranges from 1.2 to 3.3 years of age instead of 3e5 years of age as advertised in the previous version of the paper.This change has an effect on the force of infection generated by this model.In this corrigendum,we demonstrate the correct method to calculate the average age at first infection for the model.We compare the forces of infection that correspond to these ages in our model with the forces of infection in other endemic populations.We show that the modified age range corresponds to forces of infection which are higher than those that are known to exist in historical studies of polioendemic regions.Thus,the results in the paper have limited applicability to real-world endemic situations.
基金This research was supported in part by the Army Research Office under MURI grant 558153-MA-MUR,Prime Award W91 INF-11-1-0036.
文摘Background:Small populations that have been isolated by conflict make vaccination and surveillance difficult,threatening polio eradication.Silent circulation is caused by asymptomatic infections.It is currently not clear whether the dynamics of waning immunity also influence the risk of silent circulation in the absence of vaccination.Such circulation can,nevertheless,be present following a declaration of elimination as a result of inadequate acute flaccid paralysis surveillance(AFPS)or environmental surveillance(ES).Methods:We have constructed a stochastic model to understand how stochastic effects alter the ability of small populations to sustain virus circulation in the absence of vaccination.We analyzed how the stochastic process determinants of the duration of silent circulation that could have been detected by ES were affected by R0,waning dynamics,population size,and AFPS sensitivity in a discrete individual stochastic model with homogeneous contagiousness and random mixing.We measured the duration of silent circulation both by the interval between detected acute flaccid paralysis(AFP)cases and the duration of circulation until elimination.Results:As R0 increased and population size increased,the interval between detected AFP cases and the duration of circulation until elimination increased.As AFPS detection rates decreased,the interval between detected AFP cases increased.There was up to a 22%chance of silent circulation lasting for more than 3 years with 100%AFP detection.The duration of silent circulation was not affected by the waning immunity dynamics.Conclusion:We demonstrated that small populations have the potential to sustain prolonged silent circulation.Surveillance in these areas should be intensified before declaring elimination.To further validate these conclusions,it is necessary to realistically relax the simplifying assumptions about mixing and waning.
文摘目的分析中国（未包括香港、澳门特别行政区和台湾地区，下同）实现无脊髓灰质炎（脊灰）目标后，疫苗衍生脊灰病毒（Vaccine—derived Poliovirus，VDPV）的发生情况。方法分析31个省（自治区、直辖市，下同）报告的急性弛缓性麻痹（Acute Flaccid Paralysis，AFP）病例数据库、中国疾病预防控制中心（Center for Disease Control and Prevention，CDC）病毒病预防控制所国家脊灰实验室，对脊灰病毒阳性分离物的基因测序结果，各级CDC对VDPV及病例的调查和处置报告。结果2001～2013年，中国AFP病例监测系统从37名儿童粪便标本中分离到VDPV，来源于12个省，其中AFP病例22例，AFP病例接触者13人，健康儿童2人。其中2004年贵州省2例Ⅰ型（Type1）VDPV（VDPVI）病例形成循环（Circulating）（cVDPVⅠ），2011～2012年四川省Ⅱ型（Type2）疫苗高变异脊灰病毒（Vaccine—hypervariable Poliovirus，VHPVⅡ）病例／VDPVⅡ病例形成cVHPVⅡ／cVDPVⅡ。结论VDPV可在健康儿童粪便中检出，也能导致儿童麻痹。其发生有疫苗因素，也有受种者因素和疫苗使用因素。口服脊灰减毒活疫苗（Oral Poliomyelitis Attenuated Live Vaccine，OPV）接种率低，是造成发生cVDPV的原因。只有达到人群OPV的高免疫覆盖率，通过高质量的AFP病例监测系统及时发现病例，采取有效措施及时控制疫情，才能阻断病毒的传播。
文摘目的评价2019年6月四川省凉山州Ⅱ型疫苗衍生脊髓灰质炎(脊灰)病毒循环(Circulating vaccine-derived poliovirus type II,cVDPV2)相关儿童脊灰病毒(Poliovirus,PV)中和抗体水平。方法在发生cVDPV2的雷波县田坝村选取所有1-5岁儿童,在雷波县其他地区和凉山州其他6个县采用便利抽样法抽取1-5岁儿童,采集血清标本,应用微量中和试验检测PVⅠ、PVⅡ、PVⅢ和/或cVDPV2中和抗体,分析抗体阳性率和几何平均滴度(Geometric mean titer,GMT)。结果在凉山州7个县(不包括田坝村)697名儿童中,PVⅠ、PVⅡ、PVⅢ中和抗体阳性率分别为90.8%、78.5%、85.5%,GMT分别为1∶85.1、1∶25.2、1∶37.1;各型PV抗体水平均随年龄增长而先下降再上升,且在7个县之间具有显著性差异。在雷波县田坝村52名儿童中,PVⅠ、PVⅡ、PVⅢ、cVDPV2中和抗体阳性率分别为44.2%、34.6%、38.5%、84.6%,GMT分别为1∶9.5、1∶5.1、1∶8.2、1∶89.9;在雷波县其他地区100名儿童中,相应中和抗体阳性率为分别为88.0%、75.0%、80.0%、79.0%,GMT分别为1∶69.4、1∶12.3、1∶32.5、1∶18.0。结论本起cVDPV2发生地区的儿童存在脊灰免疫空白,cVDPV2循环时间较久且传播广泛,凉山州1-5岁儿童脊灰免疫水平较低,需加强儿童脊灰预防接种工作。
