Polio survivors have poorer walking adaptability than healthy individuals

BackgroundFalling is a major health problem in polio survivors, often occurring as a result of tripping, slipping or misplaced steps. Therefore, reduced walking adaptability possibly plays an important role.Research questionDoes walking adaptability, assessed on an interactive treadmill, differ between polio survivors and healthy individuals?MethodsIn this cross-sectional study, 48 polio survivors with at least one reported fall in the past year and/or fear of falling and 25 healthy individuals of similar age walked at self-selected comfortable fixed speed on an instrumented treadmill. Walking adaptability was measured as i) target-stepping accuracy (determined as variable error [VE] in mm independent of speed) in three conditions; 0 %, 20 % and 30 % variation in step length and width, and ii) anticipatory and reactive obstacle avoidance (ObA and ObR, in percentage successfully avoided). All trials were checked for valid step detection.Results46 polio survivors (mean ± SD age: 63.2 ± 8.7 years) and 25 healthy individuals (64.3 ± 6.6 years, p = 0.585) showed valid step detection. Compared to healthy individuals (mean±SE VE: 30.6±1.2 mm), polio survivors stepped less accurately onto targets (36.4±0.9 mm, p = 0.001), especially with their least-affected leg. Polio survivors avoided fewer obstacles successfully (mean±SE ObA: 83±3 %, ObR: 59±4 %) than healthy individuals (100±0.3 %, p < 0.001 and 94±3 %, p < 0.001, respectively), with a stronger decline in success rates from anticipatory to reactive obstacle avoidance for polio survivors (p < 0.001).SignificancePolio survivors reporting falls and/or fear of falling had a demonstrably reduced walking adaptability, especially so for reactive obstacle avoidance, which requires step adjustments under high time-pressure demands. Future research should study the merit of walking-adaptability assessment to currently used clinical methods of fall-risk assessment within this population.     

Altered supraspinal motor networks in survivors of poliomyelitis: A cortico-muscular coherence study

ObjectivePoliomyelitis results in changes to the anterior horn cell. The full extent of cortical network changes in the motor physiology of polio survivors has not been established. Our aim was to investigate how focal degeneration of the lower motor neurons (LMN) in infancy/childhood affects motor network connectivity in adult survivors of polio.MethodsSurface electroencephalography (EEG) and electromyography (EMG) were recorded during an isometric pincer grip task in 25 patients and 11 healthy controls. Spectral signal analysis of cortico-muscular (EEG-EMG) coherence (CMC) was used to identify the cortical regions that are functionally synchronous and connected to the periphery during the pincer grip task.ResultsA pattern of CMC was noted in polio survivors that was not present in healthy individuals. Significant CMC in low gamma frequency bands (30–47 Hz) was observed in frontal and parietal regions.ConclusionThese findings imply a differential engagement of cortical networks in polio survivors that extends beyond the motor cortex and suggest a disease-related functional reorganisation of the cortical motor network.SignificanceThis research has implications for other similar LMN conditions, including spinal muscular atrophy (SMA). CMC has potential in future clinical trials as a biomarker of altered function in motor networks in post-polio syndrome, SMA, and other related conditions.     

Spanish newsreel NO-DO (1943-1975). The diffusion of science as a legitimizing instrument of the Franco regime: polio and other immuno-preventable diseases

The official NO-DO newsreels were screened in Spain on a weekly basis from 1943 to 1981. These official news and documentary programmes were compulsory in cinemas from the moment they were first produced until the end of the Francoist dictatorship (1975). NO-DO held an information monopoly and was used as the regime's propaganda tool to indoctrinate the population, building stories tailored to the regime's interests and masking social realities. In this study, we examined newsreels on medical subjects relating to diseases preventable by vaccination. A majority of reports centred on poliomyelitis, and two differentiated periods could be defined, coinciding with the development of Franco regime's foreign policy. Further, from the gender perspective, we analyse the female stereotypes in the battle against vaccine preventable diseases Therefore, the news coverage of polio is of special relevance. In conclusion, this topic offers a good opportunity to reflect on the political role of popular science and science communication in a specific historical context.     

Enhancing viral vaccine production using engineered knockout vero cell lines – A second look

The global adoption of vaccines to combat disease is hampered by the high cost of vaccine manufacturing. The work described herein follows two previous publications (van der Sanden et al., 2016; Wu et al., 2017) that report a strategy to enhance poliovirus and rotavirus vaccine production through genetic modification of the Vero cell lines used in large-scale vaccine manufacturing. CRISPR/Cas9 gene editing tools were used to knockout Vero target genes previously shown to play a role in polio- and rotavirus production. Subsequently, small-scale models of current industry manufacturing systems were developed and adopted to assess the increases in polio- and rotavirus output by multiple stable knockout cell lines. Unlike previous studies, the Vero knockout cell lines failed to achieve desired target yield increases. These findings suggest that additional research will be required before implementing the genetically engineered Vero cell lines in the manufacturing process for polio- and rotavirus vaccines to be able to supply vaccines at reduced prices.     

Global polio eradication: Where are we in Europe and what next?

The world was never so close to reach the polio eradication: only 37 cases notified in 2016 in only three countries, but the game is not yet at the end. The risk of polio outbreaks in the EU is smaller than it has ever been in the past, but it is not so small that we can ignore it. The EU MS must remain alert and plan and prepare for managing polio events or outbreaks because of the possible dire consequences. The IPV only vaccination schedule universally applied in EU has achieved satisfactory coverage, but constantly leaving small accumulating pockets of susceptible individuals. Moreover the IPV only schedule is not an absolute barrier against poliovirus silent transmission as demonstrated in the recent Israel outbreak. The availability of annually revised S.O.P. from WHO GPEI on the identification and response of a polio event, without local poliovirus transmission or a polio outbreak with sustained transmission, helps and challenge EU countries to update their polio national preparedness plans. The EU/EEA area, in fact, is a peculiar area regarding the polio risk both for its vaccination policy, the large polio vaccines manufactures and the constant immigration from areas at polio high risk, but also EU include cultural and financial potentials crucial to sustain the polio end game strategy and reach the benefit of a world without polio risk. Poliovirus eradication will continue to be challenged as long as there is the worldwide presence of polioviruses in laboratories and vaccine production plants. Most of the world’s OPV vaccines are produced in the EU and many laboratories and research centers store and handle polio viruses. EU Member States are engaged actively in implementing the poliovirus biocontainment plans that are part of the polio eradication strategy and to certify the destruction of poliovirus strains and potentially contaminated biological materials.     

Assessment of poliovirus antibody seroprevalence in polio high risk areas of West Africa

We conducted a serological survey of anti-polio antibodies in polio high-risk areas of Mali, Guinea and Cote d’Ivoire to assess risk of future poliovirus outbreaks.Random community sampling of children 6–11 and 36–48 months-old was conducted; neutralizing antibodies against poliovirus were detected using microneutralization assay.We analysed 1059/1064 (99.5%) of enrolled children. Seroprevalence to poliovirus type 1 (PV1) across all age groups and locations ranged between 92 and 100%, for PV2 it was 77–100%, and 89–95% for PV3. PV2 seroprevalence in the younger age group in Guinea and Cote d’Ivoire was <80%. History of <4 polio vaccine doses and acute malnutrition were associated with seronegativity (OR = 2.1 CI95% = 1.5–3.1, OR = 1.8 CI95% = 1.1–3.3 respectively).The risk of poliovirus outbreak following importation is low because of high population immunity to PV1, however, due to large cohort of PV2 seronegative children any future detection of vaccine-derived poliovirus type 2 requires urgent response to arrest rapid spread.     

New insights into physiopathology of immunodeficiency-associated vaccine-derived poliovirus infection; systematic review of over 5 decades of data

Widespread administration of oral poliovirus vaccine (OPV) has decreased global incidence of poliomyelitis by ≈99.9%. However, the emergence of vaccine-derived polioviruses (VDPVs) is threatening polio-eradication program. Primary immunodeficiency (PID) patients are at higher risks of vaccine-associated paralytic poliomyelitis (VAPP) and prolonged excretion of immunodeficiency-associated VDPV (iVDPV).We searched Embase, Medline, Science direct, Scopus, Web of Science, and CDC and WHO databases by 30 September 2016, for all reports of iVDPV cases. Patient-level data were extracted form eligible studies. Data on immunization coverage and income-level of countries were extracted from WHO/UNICEF and the WORLD BANK databases, respectively. We assessed bivariate associations between immunological, clinical, and virological parameters, and exploited multivariable modeling to identify independent determinants of poliovirus evolution and patients’ outcomes. Study protocol was registered with PROSPERO (CRD42016052931).4329 duplicate-removed titles were screened. A total of 107 iVDPV cases were identified from 68 eligible articles. The majority of cases were from higher income countries with high polio-immunization coverage. 74 (69.81%) patients developed VAPP. Combined immunodeficiency patients showed lower rates of VAPP (p < .001) and infection clearance (p = .02), compared to humoral immunodeficiency patients. The rate of poliovirus genomic evolution was higher at early stages of replication, decreasing over time until reaching a steady state. Independent of replication duration, higher extent (p = .04) and rates (p = .03) of genome divergence contributed to a less likelihood of virus clearance. PID type (p < .001), VAPP occurrence (p = .008), and income-level of country (p = .04) independently influenced patients’ survival.With the use of OPV, new iVDPVs will emerge independent of the rate of immunization coverage. Inherent features of PIDs contribute to the clinical course of iVDPV infection and virus evolution. This finding could shed further light on poliomyelitis pathogenesis and iVDPV evolution pattern. It also has implications for public health, the polio eradication effort and the development of effective antiviral interventions.     

中国2001～2013年疫苗衍生脊髓灰质炎病毒及病例流行病学特征分析

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。     

中国2012年脊髓灰质炎实验室网络的运转与评价

目的通过对中国2012年脊髓灰质炎（脊灰）实验室网络（Polio Laboratory Network,PLN）监测数据（未包括香港、澳门特别行政区和台湾地区,下同）进行统计分析,评估其运转情况,为中国重新恢复无脊灰状态提供实验室依据。方法分析中国免疫规划监测信息管理系统数据库中,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）病例个案调查表和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（National Polio Laboratory,NPL）的监测数据库,总结PLN运转中的质量控制,评价PLN的各项运转指标。结果中国2012年PLN共收集了6163例AFP病例的12204份粪便标本,14d内双份粪便标本采集率为92．6％,合格粪便标本采集率为92．1％。按世界卫生组织（World Health Organization,WHO）第4版《脊灰实验室手册》的要求进行病毒分离和鉴定,试验结果28d内及时反馈率为99％。2012年,在116例AFP病例粪便标本中分离到脊灰病毒（Poliovirus,PV）,分离率为2．10％（116／5534）;在680例AFP病例粪便标本中分离到非脊灰肠道病毒（Non—polio Enterovirus,NPEV）,分离率为12．29％（680／5534）。2012年,NPL收到PLN送检的283株PV,对375株单血清型PV采用衣壳蛋白（Capsid Protein）VP1编码区核苷酸序列测定与分析进行型内鉴定（Intratypic Differentiation,ITD）,发现7例（共计25株）疫苗衍生（Vaccine—derived）PV（VDPV）,其中Ⅰ型2株,Ⅱ型16株,Ⅲ型7株,未发现野生型（Wild Type）PV（WPV）。2012年,NPL收到环境监测送检的314株PV,全部采用VP1编码区核苷酸序列测定与分析进行ITD,在山东省发现1株VDPV。2012年8月,NPL作为WHO西太平洋区脊灰参比实验室接受并以优异的成绩通过了WHO的年度现场认证;2012年10月,NPL以满分的成绩通过了荧光定量聚合酶链反应（Polymerase Chain Reaction,PCR）和VDPV筛查的职能考核;2012年12月,又以满分通过了WHO核苷酸序列测定和分析的第一次职能考核。在中国PLN中,有11个省级CDC脊灰实验室参加并通过了WHO的实验室现场评估认证;22个省级CDC脊灰实验室参加并以满分的成绩通过了荧光定量PCR和VDPV筛查的职能考核。2012年10月9日,WHO通过对中国AFP病例监测质量和结果的评估,宣布中国重新恢复无脊灰状态。结论2012年,PLN运转正常、敏感有效,在AFP病例和环境监测中未发现WPV,为中国恢复无脊灰状态提供了关键的技术支撑作用。