BACKGROUND & AIMS: Background:Recent detections of circulating serotype 2 vaccine-derived poliovirus in northern Nigeria (Borno and Sokoto states) and Pakistan (Balochistan Province) and serotype 1 wild poliovirus in Pakistan, Afghanistan, and Nigeria (Borno) represent public health emergencies that require aggressive response. Methods:We demonstrate the importance of undervaccinated subpopulations, using an existing dynamic poliovirus transmission and oral poliovirus vaccine evolution model. We review the lessons learned during the polio endgame about the role of subpopulations in sustaining transmission, and we explore the implications of subpopulations for other vaccine-preventable disease eradication efforts. Results:Relatively isolated subpopulations benefit little from high surrounding population immunity to transmission and will sustain transmission as long as they do not attain high vaccination coverage. Failing to reach such subpopulations with high coverage represents the root cause of polio eradication delays. Achieving and maintaining eradication requires addressing the weakest links, which includes immunizing populations in insecure areas and/or with disrupted or poor-performing health systems and managing the risks of individuals with primary immunodeficiencies who can excrete vaccine-derived poliovirus long-term. Conclusions:Eradication efforts for vaccine-preventable diseases need to create performance expectations for countries to immunize all people living within their borders and maintain high coverage with appropriate interventions.Keywords. Polio; eradication; transmission; heterogeneity.

背景与目标： 背景：最近在尼日利亚北部（博尔诺州和索科托州）和巴基斯坦（巴洛克希斯坦省）检测到循环的血清型2疫苗源性脊髓灰质炎病毒，在巴基斯坦，阿富汗和尼日利亚（博尔诺）发现了血清型1型野生脊髓灰质炎病毒，这代表了需要紧急响应的公共卫生紧急情况。
方法：我们使用现有的动态脊髓灰质炎病毒传播和口服脊髓灰质炎病毒疫苗进化模型证明了接种不足的亚群的重要性。我们回顾了在小儿麻痹症终末期中学到的有关亚群在维持传播中的作用的经验教训，并探讨了亚群对其他疫苗可预防的疾病消除工作的影响。
结果：相对分离的亚群受益于周围人群对传播的高度免疫力，只要他们没有获得较高的疫苗接种覆盖率，它们就会维持传播。未能以较高的覆盖率到达此类亚群是根除脊髓灰质炎根除延误的根本原因。要实现和保持根除工作，必须解决最薄弱的环节，其中包括对不安全地区和/或卫生系统受到破坏或运行不佳的人群进行免疫接种，以及管理具有主要免疫缺陷的人的风险，这些人可以长期排出疫苗衍生的脊髓灰质炎病毒。
结论：根除疫苗可预防疾病的努力需要为各国创造绩效期望，以使所有居住在其境内的人们获得免疫，并通过适当的干预措施保持较高的覆盖率。脊髓灰质炎;消灭；传播;异质性。

BACKGROUND & AIMS: :The Immunization Systems Management Group (IMG) was established to coordinate and oversee objective 2 of the Polio Eradication and Endgame Strategic Plan 2013-2018, namely, (1) introduction of ≥1 dose of inactivated poliovirus vaccine in all 126 countries using oral poliovirus vaccine (OPV) only as of 2012, (2) full withdrawal of OPV, starting with the withdrawal of its type 2 component, and (3) using polio assets to strengthen immunization systems in 10 priority countries. The IMG's inclusive, transparent, and partnership-focused approach proved an effective means of leveraging the comparative and complementary strengths of each IMG member agency. This article outlines 10 key factors behind the IMG's success, providing a potential set of guiding principles for the establishment and implementation of other interagency collaborations and initiatives beyond the polio sphere.

背景与目标： ：成立了免疫系统管理小组（IMG），以协调和监督《 2013-2018年消灭脊灰和残局战略计划》的目标2，即（1）在所有126个国家中使用口服脊髓灰质炎病毒引入≥1剂灭活脊髓灰质炎疫苗仅从2012年起开始使用疫苗（OPV），（2）从其2型成分的退出开始全面撤消OPV，（3）在10个优先国家/地区使用脊髓灰质炎资产来加强免疫系统。 IMG的包容性，透明性和以伙伴关系为重点的方法证明是一种有效的手段，可以利用每个IMG成员机构的比较优势和互补优势。本文概述了IMG成功背后的10个关键因素，为在脊髓灰质炎领域之外建立和实施其他机构间合作和倡议提供了一组潜在的指导原则。

BACKGROUND & AIMS: :In the USA, California's highly-regarded Tobacco Control Program (CTCP) has defined its goal as "ending the tobacco epidemic for all population groups" by 2035. To understand local advocates' perceptions of endgame-oriented policies, we interviewed 28 advocates from California communities that had recently adopted tobacco control policies. There was no consensus among participants on which specific policies would constitute the tobacco endgame in California. There was an agreement, however, that policymakers should promote policies that would impact communities with the highest tobacco use prevalence and that policies should be 'clean', avoiding exemptions. Participants were cognizant of California's history of tobacco control policy innovations beginning locally and eventually being adopted at the state level. Many commented that recent policy innovations in the state had begun a conversation that made more 'radical' ideas seem possible. California tobacco control advocates are engaged in local endgame policy discussions and prepared to advance California's endgame goal.

背景与目标： ：在美国，加利福尼亚州备受推崇的烟草控制计划（CTCP）将其目标定义为“到2035年消除所有人群的烟草流行”。为了了解当地倡导者对以禁毒为导向的政策的看法，我们采访了来自28个倡导者最近采用了烟草控制政策的加利福尼亚社区。参与者之间没有达成共识，即哪些具体政策将构成加利福尼亚的烟草终结游戏。但是，达成了一项协议，政策制定者应提倡对烟草使用率最高的社区产生影响的政策，并且政策应“干净”，避免豁免。参与者认识到加利福尼亚的烟草控制政策创新历史始于本地，并最终在州一级被采用。许多人评论说，该州最近的政策创新已经开始了对话，使更多“激进”的想法似乎成为可能。加州烟草控制倡导者正在参与当地的禁毒政策讨论，并准备推进加利福尼亚的禁毒目标。

BACKGROUND & AIMS: :The Polio Endgame Strategy 2019-2023 has been developed. However, more effective and efficient surveillance activities should be conducted with the preparedness of emergence for vaccine-derived poliovirus (VDPV) or wild poliovirus (WPV). We reviewed the impact of the case-based acute flaccid paralysis (AFP) surveillance (1991 to 2018) and environmental surveillance (2011 to 2018) in polio eradication in Shandong province of China. Clinical characteristics of AFP cases and enterovirus (EV) investigation of research samples were assessed. During the period, 10,224 AFP cases were investigated, and 352 sewage samples were collected. The nonpolio AFP rate sustained at over 2.0/100,000 since 1997. Of 10,224 cases, males and young children experienced a higher risk of severe diseases, and 68.5% suffered lower limb paralysis. We collected 1,707 EVs from AFP cases, including 763 polioviruses and 944 nonpolio enteroviruses (NPEVs). No WPV was isolated since 1992. The AFP surveillance showed high sensitivity in detecting 143 vaccine-associated paralytic poliomyelitis (VAPP) cases and 6 VDPVs. For environmental surveillance, 217 (61.6%) samples were positive for poliovirus, and altogether, 838 polioviruses and 2,988 NPEVs were isolated. No WPV was isolated in environmental surveillance, although one VDPV2 was identified. Phylogenetic analysis revealed environmental surveillance had the capacity to detect a large scope of NPEVs. The case-based AFP surveillance will be indispensable for detecting VAPP cases and VDPV circulation in countries using oral polio vaccine. Environmental surveillance is advantageous in identifying EV circulation and responding to ongoing circulating VDPV outbreaks and should be expanded to complement the AFP surveillance.IMPORTANCE Interrupting wild poliovirus transmission and stopping circulating vaccine-derived poliovirus (cVDPV) outbreaks have been proposed as two global goals by the World Health Organization in the Global Polio Eradication Initiative (GPEI). This analysis, based on the 28-year acute flaccid paralysis (AFP) surveillance and 8-year environmental surveillance, provides continued high-quality surveillance performance in achieving the GPEI and detecting the circulation of enterovirus. Given the ongoing cVDPV outbreaks in the world, we present the surveillance capacity of environmental surveillance in capturing enterovirus circulation. The final poliovirus (especially VDPV) elimination has become increasingly complex, and the case-based AFP surveillance alone will lead to difficulties in early detecting dynamics of poliovirus transmission and monitoring the extent of environmental circulation. This study goes beyond previous work to provide a detailed comprehensive evaluation of the enterovirus surveillance and can be used to formulate a set of implementation plan and performance indicators for environmental surveillance.

背景与目标： ：已经制定了《 2019-2023年小儿麻痹症残局策略》。但是，应该为疫苗衍生的脊髓灰质炎病毒（VDPV）或野生脊髓灰质炎病毒（WPV）的出现做好准备，进行更有效的监视活动。我们回顾了基于病例的急性弛缓性麻痹（AFP）监测（1991年至2018年）和环境监测（2011年至2018年）在中国山东省消灭脊髓灰质炎的影响。评估了AFP病例的临床特征和研究样本的肠道病毒（EV）调查。在此期间，调查了10224例AFP病例，收集了352个污水样品。自1997年以来，非政治性AFP比率一直维持在2.0 / 100,000以上。在10,224例病例中，男性和幼儿患严重疾病的风险更高，下肢瘫痪的发生率为68.5％。我们从AFP病例中收集了1,707辆EV，包括763例脊髓灰质炎病毒和944例非策略性肠道病毒（NPEV）。自1992年以来未分离出WPV。AFP监测显示出对143例疫苗相关性麻痹性脊髓灰质炎（VAPP）病例和6例VDPV的高度敏感性。对于环境监测，有217例（61.6％）样本的脊髓灰质炎病毒呈阳性，共分离出838例脊髓灰质炎病毒和2,988台NPEV。尽管发现了一个VDPV2，但在环境监测中没有隔离WPV。系统发育分析表明，环境监测具有检测大范围NPEV的能力。在使用口服脊髓灰质炎疫苗的国家中，基于病例的AFP监视对于检测VAPP病例和VDPV流通将是必不可少的。环境监测有利于识别EV循环并应对持续的循环VDPV暴发，应加以扩大以补充AFP监测。世界卫生组织参与的全球根除脊髓灰质炎行动（GPEI）。该分析基于28年急性弛缓性麻痹（AFP）监测和8年环境监测，在实现GPEI和检测肠病毒循环方面提供了持续的高质量监测性能。鉴于世界范围内持续不断的cVDPV暴发，我们介绍了环境监测在捕获肠道病毒循环中的监测能力。最终消除脊髓灰质炎病毒（尤其是VDPV）变得越来越复杂，仅基于病例的AFP监视将导致在早期检测脊髓灰质炎病毒传播的动态以及监测环境循环程度方面遇到困难。这项研究超出了先前的工作范围，可提供对肠道病毒监测的详细全面评估，并可用于制定一套环境监测的实施计划和性能指标。

BACKGROUND & AIMS: PURPOSE OF REVIEW:Focusing on the key developments since January 2019, this review aims to inform policymakers and clinical practitioners on the latest on evolving global polio epidemiology and scientific advancements to guide strategies for eradication. RECENT FINDINGS:An upsurge in wild poliovirus type 1 cases in Pakistan and Afghanistan and an expansion of type 2 circulating vaccine-derived poliovirus transmission in multiple countries threaten the remarkable progress made over past several decades by the global eradication program. These challenges have also spurred innovation on multiple fronts, including earlier detection, enhanced environmental surveillance and safer and more affordable vaccine options. SUMMARY:A concerted effort to adapt program strategies to address context-specific challenges and continued focus on innovations to enhance detection and response capabilities will be the key to achieve and sustain eradication of all types of polioviruses.

背景与目标： 审查的目的：本次审查的重点是自2019年1月以来的主要进展，旨在向政策制定者和临床医生提供有关不断发展的全球脊髓灰质炎流行病学和科学进展的最新信息，以指导消灭策略。
最近的发现：在巴基斯坦和阿富汗，野生脊髓灰质炎病毒1型病例激增，以及在多个国家/地区传播的2型循环疫苗衍生脊髓灰质炎病毒传播的扩大，威胁了全球消灭计划在过去几十年中取得的显着进展。这些挑战也刺激了多个方面的创新，包括更早发现，增强环境监测以及更安全，更实惠的疫苗选择。
摘要：作出协调一致的努力来调整计划策略以应对特定环境的挑战，并继续关注创新以增强检测和响应能力，这将是实现和持续消除所有类型的脊髓灰质炎病毒的关键。

BACKGROUND & AIMS: BACKGROUND:China's Expanded Program on Immunization (EPI) has provided 4 doses of oral poliovirus vaccine (OPV) since the 1970s. Inactivated poliovirus vaccine (IPV) became available in 2010 in Hangzhou as a private-sector, parent-chosen alternative to OPV. In 2015, WHO recommended that countries with all-OPV vaccination schedules introduce at least one dose of IPV, to mitigate risk associated with the withdrawal of type 2 OPV. We analyzed polio vaccine coverage and utilization in Hangzhou to determine patterns of IPV use and the occurrence of vaccine-associated paralytic polio (VAPP) in the various patterns identified. METHODS:Children born between 2010 and 2014 and registered in Hangzhou's Immunization Information System (HZIIS) were included. VAPP cases were detected through the acute flaccid paralysis surveillance system. We used descriptive epidemiological methods to determine IPV and OPV usage patterns and VAPP occurrence. RESULTS:HZIIS data from 566,894 children were analyzed. Coverage levels of polio vaccine were greater than 92% for each birth cohort. Percentages of children using OPV-only, IPV-only, and IPV/OPV sequential schedules were 70.57%, 27.01% and 2.41%, respectively. IPV-only schedule utilization increased by birth cohort regardless of geographical area or whether the child was locally-born. The highest use of an all-IPV schedule (79.85%) was among urban, locally-born children in the 2014 birth cohort. Five VAPP cases were identified during the study years; all cases occurred following the first polio vaccine dose, which was always OPV for the cases. Type 2 vaccine virus was isolated from 2 VAPP cases, and type 2 and type 3 vaccine virus was isolated from one VAPP case. The incidence of VAPP in the 2010-2014 birth cohorts was 3.76 per 1million doses of OPV. CONCLUSION:Children in Hangzhou had high polio vaccination coverage. IPV-only schedule use increased by year, and was highest in urban areas among locally-born children. All cases of VAPP were associated with the first dose of OPV.

背景与目标： 背景：自1970年代以来，中国的扩大免疫规划（EPI）已提供了4剂口服脊髓灰质炎病毒疫苗（OPV）。灭活的脊髓灰质炎病毒疫苗（IPV）于2010年在杭州上市，作为私营部门的父母选择的OPV替代品。在2015年，世卫组织建议制定了全OPV疫苗接种计划的国家至少注射一剂IPV，以减轻与撤回2型OPV有关的风险。我们分析了杭州的脊髓灰质炎疫苗覆盖率和利用情况，以确定了IPV的使用模式以及所确定的各种模式中与疫苗相关的麻痹性脊髓灰质炎（VAPP）的发生。
方法：纳入2010年至2014年之间出生并在杭州市免疫信息系统（HZIIS）中注册的孩子。通过急性弛缓性麻痹监测系统发现了VAPP病例。我们使用描述性流行病学方法来确定IPV和OPV使用模式以及VAPP的发生。
结果：分析了566894名儿童的HZIIS数据。每个出生队列的脊髓灰质炎疫苗覆盖率大于92％。使用仅使用OPV，仅使用IPV和IPV / OPV顺序时间表的儿童的百分比分别为70.57％，27.01％和2.41％。无论出生地区或孩子在当地出生，仅按IPV计划的使用率都会随出生队列的增加而增加。在2014年出生的队列中，所有IPV计划的使用率最高（79.85％）在城市本地出生的儿童中。在研究年中发现了五例VAPP病例；所有病例均在第一剂脊髓灰质炎疫苗之后发生，对于该病例，该剂量始终为OPV。从2例VAPP病例中分离出2型疫苗病毒，从1例VAPP病例中分离出2型和3型疫苗病毒。每100万剂OPV中，2010-2014年出生队列中VAPP的发生率为3.76。
结论：杭州市儿童脊髓灰质炎疫苗接种率较高。仅使用IPV的时间表使用量逐年增加，在本地出生的儿童中，城市使用率最高。所有VAPP病例均与第一剂OPV相关。

BACKGROUND & AIMS: INTRODUCTION:Managing the polio endgame requires access to sufficient quantities of poliovirus vaccines. After oral poliovirus vaccine (OPV) cessation, outbreaks may occur that require outbreak response using monovalent OPV (mOPV) and/or inactivated poliovirus vaccine. Areas covered: We review the experience and challenges with managing vaccine supplies in the context of the polio endgame. Building on models that explored polio endgame risks and the potential mOPV needs to stop outbreaks from live poliovirus reintroductions, we conceptually explore the potential demands for finished and bulk mOPV doses from a stockpile in the context of limited shelf-life of finished vaccine and time delays to convert bulk to finished vaccine. Our analysis suggests that the required size of the mOPV stockpile varies by serotype, with the highest expected needs for serotype 1 mOPV. Based on realizations of poliovirus risks after OPV cessation, the stockpile required to eliminate the chance of a stock-out appears considerably larger than the currently planned mOPV stockpiles. Expert commentary: The total required stockpile size depends on the acceptable probability of a stock-out, and increases with longer times to finish bulk doses and shorter shelf-lives of finished doses. Successful polio endgame management will require careful attention to poliovirus vaccine supplies.

背景与目标： 简介：管理小儿麻痹症终末期需要获得足够数量的小儿麻痹症病毒疫苗。口服脊髓灰质炎病毒疫苗（OPV）停止后，可能发生暴发，需要使用单价OPV（mOPV）和/或灭活的脊髓灰质炎病毒疫苗应对暴发。涵盖的领域：我们回顾了在小儿麻痹症残局背景下管理疫苗供应的经验和挑战。基于探索脊髓灰质炎终末期风险和潜在mOPV需阻止活脊灰病毒再引入爆发的模型的模型，我们从概念上探讨了在成品疫苗保质期有限和时间延迟的情况下，库存对成品和批量mOPV剂量的潜在需求将散装疫苗转变为成品疫苗。我们的分析表明，所需的mOPV贮藏量因血清型而异，血清型1 mOPV的预期需求最高。基于OPV停止后脊髓灰质炎病毒风险的认识，消除当前缺货机会所需的库存似乎比当前计划的mOPV库存要大得多。专家评论：总所需储备量取决于可接受的缺货概率，并且随着完成批量剂量的时间增加和完成剂量的货架期缩短而增加。成功的脊髓灰质炎终末管理将需要特别注意脊髓灰质炎疫苗的供应。

BACKGROUND & AIMS: :The aim of this study was to investigate the anti-proliferative, apoptotic, cytotoxic, and anti-oxidant effects of extracts from the lichen Cladonia pocillumon human breast cancer cells (MCF-7), and to characterize the anti-microbial features.  MCF-7 cells were treated with methanolic C. pocillum extract for 24h. The cytotoxicity of the extract was tested with MTT. Moreover, its anti-proliferative effects were examined with immunocytochemical method. Apoptosis and biochemical parameters were detected in MCF-7. The methanol and chloroform extracts of the lichen were tested for anti-microbial activity against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans using the disc diffusion method and calculation of minimal inhibitory concentrations. Although BrdU incorporation was not observed in MCF-7 cells treated with methanol extract at a concentration above 0.2 mg/mL, a significant decrease was observed int he percentage of PCNA immunoreactive cells in groups treated with 0.2, 0.4, 06, and 0.8 mg/mL methanol extracts of C.pocillum (49±6.3, 44±5.2, 23±2.5, 0, respectively) compared to that of control (85±4.5). The percentage of apoptotic cells significantly increased in groups treated with 0.2, 0.4, 0.6, and 0.8 mg/mL extracts of the C.pocillum (54±3.5, 76±2.6, 77±1.8, 82±4.2, respectively) compared with that of control group (3.9±1.5).The half-maximal inhibitory concentration of the methanol extract against MCF-7 cells was 0.802 mg/mL .Although the chloroform extract showed more effective anti-microbial activity overall, the methanol extract showed higher anti-fungal activity. Collectively, the results of our study indicate that C.pocillum extracts have strong anti-microbial and apoptotic effects. This lichen therefore shows potential for development as a natural anti-microbial, anti-oxidant, and apoptotic agent.

背景与目标： ：这项研究的目的是研究地衣人子草Cladonia pocillumon人乳腺癌细胞（MCF-7）提取物的抗增殖，凋亡，细胞毒性和抗氧化作用，并表征其抗微生物特性。将MCF-7细胞用甲醇梭状芽孢杆菌提取物处理24小时。用MTT测试提取物的细胞毒性。此外，用免疫细胞化学方法检查了它的抗增殖作用。在MCF-7中检测凋亡和生化参数。使用圆盘扩散法并计算最小抑菌浓度，测试了地衣的甲醇和氯仿提取物对金黄色葡萄球菌，粪肠球菌，大肠杆菌，铜绿假单胞菌和白色念珠菌的抗微生物活性。尽管在浓度高于0.2 mg / mL的甲醇提取物处理的MCF-7细胞中未观察到BrdU掺入，但在0.2、0.4、06和0.8 mg / mL的组中观察到PCNA免疫反应性细胞的百分比显着降低与对照的对照（85±4.5）相比，mL的柠檬毛提取物甲醇提取物（分别为49±6.3、44±5.2、23±2.5、0）。与0.2 mg / mL，0.4 mg / mL，0.6 mg / mL和0.8 mg / mL的青花菜提取物相比，凋亡细胞的百分比显着增加（分别为54±3.5、76±2.6、77±1.8、82±4.2）。对照组（3.9±1.5）。甲醇提取物对MCF-7细胞的最大半数抑制浓度为0.802 mg / mL。尽管氯仿提取物总体上显示出更有效的抗菌活性，但甲醇提取物显示出更高的抗微生物活性。真菌活动。总体而言，我们的研究结果表明，茶树提取物具有很强的抗微生物和凋亡作用。因此，这种地衣显示出作为天然抗微生物剂，抗氧化剂和凋亡剂的发展潜力。

BACKGROUND & AIMS: :In a Perspective linked to the research article by Isobel Blake and colleagues, Elizabeth Miller and T. Jacob John discuss the path towards global polio eradication and the challenges, strategies, and necessary precautions around oral polio vaccine cessation.

背景与目标： ：在与Isobel Blake及其同事的研究文章相关的《观点》中，伊丽莎白·米勒和T.雅各布·约翰讨论了全球消灭小儿麻痹症的途径以及戒除小儿麻痹症疫苗的挑战，策略和必要的预防措施。