关键词： poliovirus   sequencing   evolution   transmission bottlenecks   live vaccines   vaccine evolution  

摘要： The emergence of circulating vaccine-derived polioviruses through evolution of the oral polio vaccine (OPV) poses a significant obstacle to polio eradication. Understanding the early genetic changes that occur as OPV evolves and transmits is important for preventing future outbreaks. Here, we use deep sequencing to define the evolutionary trajectories of type 2 OPV in a vaccine trial. By sequencing 497 longitudinal stool samples from 271 OPV2 recipients and household contacts, we were able to examine the extent of convergent evolution in vaccinated individuals and the amount of viral diversity that is transmitted. In addition to rapid reversion of key attenuating mutations, we identify strong selection at 19 sites across the genome. We find that a tight transmission bottleneck limits the onward transmission of these early adaptive mutations. Our results highlight the distinct evolutionary dynamics of live attenuated virus vaccines and have important implications for the success of next-generation OPV.

关键词： Inactivated polio vaccine   Fractional dose   Vaccination   Campaign   Pakistan  

摘要： BackgroundInactivated Polio Vaccine (IPV) campaign was conducted in February 2019 in Karachi where needle-free injectors were introduced for the administration of the fractional dose of IPV (fIPV) on a large scale. This study aimed to determine the impact of needle-free injectors on vaccination *** four towns of Karachi, fIPV was given using needle-free injectors "PharmaJet Tropis ID". Whereas, in six towns full dose of IPV was administered to children of 4-59months of age. Cluster surveys through rapid convenience assessment method were conducted after the completion of vaccination *** total of 33,815 households' data was analyzed. Among these, 27,650 (82.8%) children were vaccinated. In fIPV areas, 85.3% of children were vaccinated compared to 79.5% in full dose IPV areas. A comparison of reasons for unvaccinated showed that 1.6% of parents do not give importance to vaccination in fIPV areas compared to 4.2% in full IPV areas (p-value <0.0001). More children were not vaccinated due to fear of injection 1.8% in full IPV areas compared to 0.7% in fIPV areas (p-value <0.0001). The source of campaign information shows that more frequent mobile miking 3.1% was observed in fIPV areas compared to 0.4% in full IPV areas (p-value <0.0001).ConclusionsOur analysis supports the fractional dose of IPV in mass campaigns to achieve good vaccination coverage especially using needle-free injectors "PharmaJet Tropis ID" and vigorous social mobilization activities are expedient in accomplishing high coverage.

摘要： Background Two novel type 2 oral poliovirus vaccine (OPV2) candidates, novel OPV2-c1 and novel OPV2-c2, designed to be more genetically stable than the licensed Sabin monovalent OPV2, have been developed to respond to ongoing polio outbreaks due to circulating vaccine-derived type 2 polioviruses. Methods We did two randomised studies at two centres in Belgium. The first was a phase 4 historical control study of monovalent OPV2 in Antwerp, done before global withdrawal of OPV2, and the second was a phase 2 study in Antwerp and Ghent with novel OPV2-c1 and novel OPV2-c2. Eligible participants were healthy adults aged 18-50 years with documented history of at least three polio vaccinations, including OPV in the phase 4 study and either OPV or inactivated poliovirus vaccine (IPV) in the novel OPV2 phase 2 study, with no dose within 12 months of study start. In the historical control trial, participants were randomly assigned to either one dose or two doses of monovalent OPV2. In the novel OPV2 trial, participants with previous OPV vaccinations were randomly assigned to either one or two doses of novel OPV2-c1 or to one or two doses of novel OPV2-c2. IPV-vaccinated participants were randomly assigned to receive two doses of either novel OPV2-c1, novel OPV2-c2, or placebo. Vaccine administrators were unmasked to treatment;medical staff performing safety and reactogenicity assessments or blood draws for immunogenicity assessments were masked. Participants received the first vaccine dose on day 0, and a second dose on day 28 if assigned to receive a second dose. Primary objectives were assessments and comparisons of safety up to 28 days after each dose, including solicited adverse events and serious adverse events, and immunogenicity (seroprotection rates on day 28 after the first vaccine dose) between monovalent OPV2 and the two novel OPV2 candidates. Primary immunogenicity analyses were done in the per-protocol population. Safety was assessed in the total vaccinated popul

摘要： Background Continued emergence and spread of circulating vaccine-derived type 2 polioviruses and vaccine-associated paralytic poliomyelitis from Sabin oral poliovirus vaccines (OPVs) has stimulated development of two novel type 2 OPV candidates (OPV2-c1 and OPV2-c2) designed to have similar immunogenicity, improved genetic stability, and less potential to reacquire neurovirulence. We aimed to assess safety and immunogenicity of the two novel OPV candidates compared with a monovalent Sabin OPV in children and infants. Methods We did two single-centre, multi-site, partly-masked, randomised trials in healthy cohorts of children (aged 1-4 years) and infants (aged 18-22 weeks) in Panama: a control phase 4 study with monovalent Sabin OPV2 before global cessation of monovalent OPV2 use, and a phase 2 study with low and high doses of two novel OPV2 candidates. All participants received one OPV2 vaccination and subsets received two doses 28 days apart. Parents reported solicited and unsolicited adverse events. Type 2 poliovirus neutralising antibodies were measured at days 0, 7, 28, and 56, and stool viral shedding was assessed up to 28 days post-vaccination. Primary objectives were to assess safety in all participants and non-inferiority of novel OPV2 day 28 seroprotection versus monovalent OPV2 in infants (non-inferiority margin 10%). These studies were registered with ***, NCT02521974 and NCT03554798. Findings The control study took place between Oct 23, 2015, and April 29, 2016, and the subsequent phase 2 study between Sept 19, 2018, and Sept 30, 2019. 150 children (50 in the control study and 100 of 129 assessed for eligibility in the novel OPV2 study) and 684 infants (110 of 114 assessed for eligibility in the control study and 574 of 684 assessed for eligibility in the novel OPV2 study) were enrolled and received at least one study vaccination. Vaccinations were safe and well tolerated with no causally associated serious adverse events or important medi

关键词： 小儿麻痹糖丸   脊髓灰质炎减毒活疫苗   疫苗接种   肢体残疾   接种时间   新生儿乙肝疫苗   小儿疫苗   传染病  

摘要： 我国疫苗接种的普及,有效地控制了部分传染病的发病率,避免了无数儿童的残疾和死亡。自1995年后,通过口服小儿麻痹糖丸(脊髓灰质炎减毒活疫苗),阻断了本土脊髓灰质炎病毒的传播,使成千上万的孩子避免了肢体残疾;普及新生儿乙肝疫苗的接种后,我国5岁以下的儿童乙肝病毒携带率已从1992年的9.7%降至2014年的0.3%。

关键词： 医学微生物学   课程思政   案例   脊髓灰质炎病毒   疫苗  

摘要： 为了在医学微生物学教学中实施课程思政,完成高校立德树人根本任务,针对脊髓灰质炎病毒教学内容,设计"方舟苦渡万千甜"思政案例,使学生了解我国著名病毒学家顾方舟研制脊髓灰质炎病毒疫苗的感人事迹,调动学生学习兴趣,培养学生严谨求学、无私奉献的精神,取得良好教学效果。

关键词： 肠道病毒感染   新生儿感染   埃可病毒   脊髓灰质炎病毒   无菌性脑膜炎   柯萨奇病毒   主动免疫   心肌炎  

摘要： 人类肠道病毒是一类生物学性状相似、形态最小的单正链RNA病毒,包括脊髓灰质炎病毒、柯萨奇病毒、埃可病毒和新肠道病毒。新生儿缺乏对肠道病毒的主动免疫,为易感人群。肠道病毒是夏秋季引起新生儿感染的主要病原体之一。新生儿肠道病毒感染后临床症状轻重不一、多样化,轻者仅有一过性发热、腹泻、出疹,重者导致无菌性脑膜炎、脑炎、心肌炎、凝血功能障碍等。现回顾性分析我院2017年4月至2019年9月收治的肠道病毒感染新生儿12例的病例资料,旨在为临床诊治提供参考。

关键词： Polio   Seroprevalence   India   2016   tOPV   bOPV   Switch  

摘要： Introduction: This study assessed the seroprevalence of neutralizing antibodies to all three polioviruses among the last cohort of infants aged 6-11 months who received the trivalent oral polio vaccine (OPV) before the trivalent (tOPV) to bivalent (bOPV) switch and had an opportunity to receive a full dose of inactivated poliovirus vaccine (IPV) introduced in the routine immunization schedule. Methods: Serum was tested for neutralizing antibodies against polioviruses among infants residing in three different risk-category states for poliovirus transmission in India: Bihar, a historically high-risk state for polio;Madhya Pradesh, a state with low routine immunization coverage;Chhattisgarh, with lower acute flaccid paralysis surveillance indicators. Results: A total of 1113 serum samples were tested across the three states. The overall seroprevalence was 98.5% (95% confidence interval (CI) 97.7-99.2%), 98.9% (95% CI 98.3-99.5%), and 94.4% (95% CI 93.0-95.8%) for poliovirus types 1, 2, and 3, respectively. The median antibody titres for corresponding serotypes were 575, 362, and 181. Infants who received five doses of tOPV showed respective seroprevalence rates of 98.7%, 98.7%, and 93.7% against types 1, 2, and 3 polioviruses. There was no significant difference in seroprevalence across the groups of IPV recipients. The median reciprocal titre across the groups of IPV recipients was significantly higher for poliovirus 3 (p = 0.006). Conclusions: The seroprevalence rates observed in this study are historically the highest in the series of serosurveys that India has conducted to assess population immunity against polioviruses. Poliovirus 2 seroprevalence was very high at the time of the tOPV to bOPV switch in India effected in April 2016. (C) 2020 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

关键词： Astrovirus   Sapovirus   Poliovirus   Quality evaluation   Molecular diagnosis  

摘要： Background: Astrovirus (AstV), Sapovirus (SaV) and Poliovirus (PV) are important pathogens that cause infections in children under five years of age. It is a very important task to systematically monitor and evaluate the diagnostic performance of these viruses in clinical laboratories. Methods: In our study, we performed a multicenter evaluation study among 21 laboratories across China using simulated stool samples spiked with self-designed AstV, SaV and PV pseudoviral particles. Results: The testing capability of 80.0% (16/20, AstV), 52.6% (10/19, SaV), and 25.0% (2/8, PV) of the participating laboratories were found to be "competent" in reporting correct results for all samples. The main type of errors were false negatives. None of the laboratories identified the subtypes of AstV and SaV, and six laboratories specifically identified the subtypes of PV. Lacking of well-trained personnel and adequate funding were the main challenges. From the questionnaire results, 55.6% laboratories (10/18) believe that training personnel could improve the laboratory testing performance. Conclusions: The laboratories showed a competent diagnostic performance for AstV, but inferior diagnostic performances for SaV and PV. Sensitivity of detection and the ability for virus typing should be improved clinically. Professional and standardized personnel training is urgently needed to further improve laboratory performance.