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.     

The polio vaccination story of Pakistan

BackgroundTo describe in chronological detail Pakistan’s decades long battle against poliovirus and evaluate the multiple factors impacting it.Main bodyPakistan’s fight is documented through various published research articles and reports on Pakistan’s progress in eradication of polio published by international agencies involved in elimination of poliovirus worldwide. The socioeconomic, religious, and political factors, violent religious militancy, conspiracy theories resulting in vaccine refusals are documented in detail emphasizing the ups and downs in the fight at different times since 1994 to present. Pakistan and Afghanistan are the only two countries in the world reporting cases caused by wild polio virus type 1 (WPV1) since 2017 and the only two countries that have never stopped the transmission of WPV1 Pakistan needs to work on a war footing to eliminate the disease. The need to act urgently is now being increasingly recognized by the Pakistani Government.ConclusionMany difficulties still remain. Pakistan has reached a critical stage in the fight against polio. The world will not accept any further delay or complacency as there is apprehension around the world that Pakistan may “export” polio to other countries and undermine the worldwide success in eradicating polio.     

Vaccination against serogroup B Neisseria meningitidis: Perceptions and attitudes of parents

BackgroundA vaccine against serogroup B Neisseria meningitidis, major cause of bacterial meningitis in children and adults, has recently been developed. In a context of an increasing parental mistrust against vaccinations, understanding the reason for their choices is crucial in order to improve immunization coverage. Our study aimed at evaluating parental attitudes and perceptions towards serogroup B meningococcal invasive disease vaccination.MethodsA prospective observational study was conducted in different French independent-practice medical offices (general practitioners and paediatricians) and nurseries between May 1 and December 31, 2013, using a questionnaire distributed in electronic and paper forms to parents having at least one child between the ages of 2 months and 16 years old.Results1270 parents were included, of whom 671 (52.8%) spontaneously stated to be in favour of this vaccination. Their choice was mainly justified by the severity of the disease (63.8%) and the desire to protect their child (51.7%). In multivariate analysis, the young age of parents (OR 0.949 per additional year; p < 10⁻³), the history of vaccination against serogroup C meningococcal invasive diseases (OR 6.755; p < 10⁻³), and the prior knowledge of the vaccine (OR 2.081; p = 0.001) were associated with vaccination acceptance. The main reasons for refusal were the lack of hindsight on this new vaccine (50.6%) and the fear of side effects (45.5%). After objective information on the disease and the vaccine, only 6.3% of the entire responding population would refuse to consider vaccination.ConclusionsThe spontaneous acceptance rate of vaccination against serogroup B meningococcal invasive disease is insufficient. However, after objective information by their physician or public health authorities, only a few parents would in the end be completely resistant.     

sIPV process development for costs reduction

Polio is expected to be eradicated within only a few years from now. Upon polio eradication, the use of oral polio vaccines, which can cause circulating and virulent vaccine derived polio viruses, will be stopped. From this moment onwards, inactivated polio vaccines (IPV) will be used for worldwide vaccination against polio. An increased demand for IPV is thus anticipated. As a result, process development studies regarding the IPV production process, developed in the 1960s, have intensified. Studies on yield optimization aiming at costs reduction as well as the use of alternative polio viruses, which are more biosafe for manufacturing, are actual. Here our strategy to setup a new IPV production process using attenuated Sabin polio virus strains is presented. Moreover, aspects on reduction of the costs of goods and the impact of process optimization on sIPV costs are reviewed.     

Children vaccination coverage surveys: Impact of multiple sources of information and multiple contact attempts

BackgroundMonitoring vaccination coverage is an essential component of vaccination program evaluation. In Québec (Canada), children vaccination coverage surveys are conducted every two years since 2006. The objectives of this study were to evaluate the impact of supplementing data based on vaccination booklets with data from vaccine providers, on the final estimated vaccination coverage and to compare vaccination coverage between respondents to each survey contact attempt.MethodsData from six cross-sectional surveys were used, which included 3508 children aged 2 years. Parents were invited to transcribe the information available in their child’s vaccination booklet on the questionnaire received by mail. The survey included a maximum of 4 contact attempts to obtain a response. Data were completed among vaccine providers identified by parents. The main outcome was a complete vaccination status by 24 months of age.ResultsThe addition of data from vaccine providers to those present in vaccination booklets increased the proportion of children fully vaccinated from 5.5% to 23.7% depending on the survey year. The proportion of children fully vaccinated by 24 months of age estimated among respondents to contact 1 was only 2.1% higher than the estimates among all respondents.ConclusionsWithout validation among vaccine providers for children with missing doses according to vaccination booklets, results underestimated vaccination coverage in the target population. Conducting multiple contact attempts increased the response rate but had limited impact on the validity of estimates. It would be useful in future surveys to present the coverage obtain from respondents to each contact attempt.     

Campaigns with oral polio vaccine may lower mortality and create unexpected results

Three studies from Guinea-Bissau found conflicting effects of OPV-at-birth (OPV0) on child survival. One study from 2004 suggested excess male mortality among children receiving OPV0 compared with children receiving NoOPV0 during a period of shortage of OPV. However, two subsequent studies showed beneficial effects of OPV0. In 2004, two national OPV-campaigns had been conducted in Guinea-Bissau. In a reanalysis of the 2004-study, in a survival analysis the age-adjusted mortality rate of study participants was 67% (95% CI = 42–81%) lower after the OPV-campaigns than before the campaigns. In the OPV0 group only 22% (655/3031 person-years (pyrs)) of follow-up time was “after” the OPV-campaigns whereas 55% (473/859 pyrs) of the time in the NoOPV0 group was post-campaign (p < 0.0001, Chi²). Censoring for OPV-campaigns in the original study removed excess male mortality and made the three studies more homogeneous. Overall, there is now considerable evidence that OPV, like other live vaccines, has important beneficial non-specific effects.     

重庆市不同地区人群脊髓灰质炎中和抗体水平调查

目的了解重庆市人群脊髓灰质炎（脊灰）中和抗体水平,发现脊灰免疫薄弱环节。方法根据重庆地域分布特征,随机缺陷取3个区县,每个区县7个年龄组,分别为〈1岁,1～2岁,3～4岁,5～6岁,7～14岁,15～19岁,≥20岁,每个年龄组随机抽取30名对象开展血清学检测和问卷调查。结果共调查629名对象：①Ⅰ、Ⅱ、Ⅲ型脊灰抗体几何平均值（GMT）分别为1∶77.86、1∶76.5、1∶26.41,Ⅰ、Ⅱ、Ⅲ型脊灰抗体阳性率分别为85.85%、90.78%、73.29%。②各型抗体GMT均随年龄增长呈明显下降的趋势。③男性Ⅰ、Ⅱ型脊灰抗体水平较女性高。④有疫苗免疫史人群各型抗体GMT和阳性率比无免疫史和不详的人群高。⑤Ⅰ型和Ⅲ型脊灰抗体阳性率在地域分布上差异有统计学意义（P〈0.05）。结论调查地区人群脊灰中和抗体阳性率70.00%以上、GMT总体保持在较高水平,但是各型抗体GMT均随年龄增长呈明显下降的趋势;在经济地理环境较差的地区,应加强脊灰疫苗接种的质量评价;针对大年龄儿童及成人适时开展补充免疫等措施保持人群较高的免疫水平。     

Safety of a quadrivalent meningococcal serogroups A,C, W and Y conjugate vaccine (MenACWY-CRM) administered with routine infant vaccinations: Results of an open-label,randomized, phase 3b controlled study in healthy infants

Background

The highest risk for invasive meningococcal disease (IMD) is in infants aged <1 year. Quadrivalent meningococcal conjugate vaccination has the potential to prevent IMD caused by serogroups A, C, W and Y. This phase 3b, multinational, open-label, randomized, parallel-group, multicenter study evaluated the safety of a 4-dose series of MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, concomitantly administered with routine vaccinations to healthy infants.

Methods

Two-month-old infants were randomized 3:1 to receive MenACWY-CRM with routine vaccines or routine vaccines alone at ages 2, 4, 6 and 12 months. Adverse events (AEs) that were medically attended and serious adverse events (SAEs) were collected from all subjects from enrollment through 18 months of age. In a subset, detailed safety data (local and systemic solicited reactions and all AEs) were collected for 7 days post vaccination. The primary objective was a non-inferiority comparison of the percentages of subjects with ≥1 severe systemic reaction during Days 1–7 after any vaccination of MenACWY-CRM plus routine vaccinations versus routine vaccinations alone (criterion: upper limit of 95% confidence interval [CI] of group difference <6%).

Results

A total of 7744 subjects were randomized with 1898 in the detailed safety arm. The percentage of subjects with severe systemic reactions was 16% after MenACWY-CRM plus routine vaccines and 13% after routine vaccines alone (group difference 3.0% (95% CI −0.8, 6.4%). Although the non-inferiority criterion was not met, post hoc analysis controlling for significant center and group-by-center differences revealed that MenACWY-CRM plus routine vaccinations was non-inferior to routine vaccinations alone (group difference −0.1% [95% CI −4.9%, 4.7%]). Rates of solicited AEs, medically attended AEs, and SAEs were similar across groups.

Conclusion

In a large multinational safety study, a 4-dose series of MenACWY-CRM concomitantly administered with routine vaccines was clinically acceptable with a similar safety profile to routine vaccines given alone.     

The muscle findings in a pediatric patient with live attenuated oral polio vaccine-related flaccid monoplegia

A pediatric patient, who was given live-attenuated oral polio vaccine twice without distinct gait disturbance during infancy, begun to present limp at 3 years. His gait disturbance became remarkable with aging. At 7 years, he was unable to dorsiflex the left ankle, and presented flaccid monoplegia of the left lower extremity, and the left Achilles tendon reflex was diminished. Magnetic resonance imaging revealed multiple crack-lines in the left anterior tibial muscle, but was unable to detect any distinct lesion at responsible level of L4, L5 and S1 anterior horn cells’ degeneration. Electromyography showed continuous fibrillation potentials, but muscle biopsy presented nearly normal in this muscle. The serum levels of polio antibody type 1 and type 2 titers were elevated 64× respectively, while the type 3 antibody titer was not elevated 4×. This patient was diagnosed as live attenuated oral polio vaccine-related flaccid monoplegia, with mild clinical course.