Immunogenicity to poliovirus type 2 following two doses of fractional intradermal inactivated poliovirus vaccine: A novel dose sparing immunization schedule

IntroductionThe polio eradication endgame strategic plan calls for the sequential removal of Sabin poliovirus serotypes from the trivalent oral poliovirus vaccine (tOPV), starting with type 2, and the introduction of ≥1 dose of inactivated poliovirus vaccine (IPV), to maintain an immunity base against poliovirus type 2. The global removal of oral poliovirus type 2 was successfully implemented in May 2016. However, IPV supply constraints has prevented introduction in 21 countries and led to complete stock-out in >20 countries.MethodsWe conducted a literature review and contacted corresponding authors of recent studies with fractional-dose IPV (fIPV), one-fifth of intramuscular dose administered intradermally, to conduct additional type 2 immunogenicity analyses of two fIPV doses compared with one full-dose IPV.ResultsFour studies were identified that assessed immunogenicity of two fIPV doses compared to one full-dose IPV. Two fractional doses are more immunogenic than 1 full-dose, with type 2 seroconversion rates improving between absolute 19–42% (median: 37%, p < 0.001) and relative increase of 53–125% (median: 82%), and antibody titer to type 2 increasing by 2–32-fold (median: 10-fold). Early age of administration and shorter intervals between doses were associated with lower immunogenicity.DiscussionOverall, two fIPV doses are more immunogenic than a single full-dose, associated with significantly increased seroconversion rates and antibody titers. Two fIPV doses together use two-fifth of the vaccine compared to one full-dose IPV. In response to the current IPV shortage, a schedule of two fIPV doses at ages 6 and 14 weeks has been endorsed by technical oversight committees and has been introduced in some affected countries.     

口含糖果对结肠镜检查前肠道准备质量的影响

目的 评价口含糖果对结肠镜检查前服用复方聚乙二醇电解质散(PEG)进行肠道准备的效果.方法 选取2018年1―12月于钦州市第一人民医院行结肠镜检查的病人160例,按照随机数字表并结合病人意愿分为观察组和对照组各80例,对照组按照结肠镜检查常规行肠道准备及服药指导,观察组在对照组基础上指导其间歇有计划地口含糖果.比较两组肠道清洁度、服药达标率(服药量≥75％)、不良反应发生率及接受再次服药意愿.结果 观察组肠道清洁度评分明显优于对照组(P<0.05).观察组低血糖(1.27％比10.52％)、恶心(18.98％比32.89％)、及呕吐(7.59％比25.00％)发生率均明显低于对照组(P<0.05).观察组服药达标率(98.73％比89.47％)、服药完成率(78.48％比63.16％)及口感满意度(82.27％比65.79％)均明显高于对照组(P<0.05).结论 结肠镜检查前有计划地间歇口含糖果可提高肠道清洁度,减少病人不良反应,提高病人口服泻药依从性.     

Immunogenicity and safety of an adjuvanted inactivated polio vaccine,IPV-Al,following vaccination in children at 2, 4, 6 and at 15–18 months

BackgroundAvailability of affordable inactivated polio vaccines (IPV) is of major importance to meet the increasing global supply needs. The results presented here demonstrate non-inferiority of a reduced-dose, aluminium hydroxide-adjuvanted IPV (IPV-Al) to standard IPV.MethodsA phase 3, observer-blinded, randomised, clinical trial was conducted in Panama in infants who received either IPV-Al (n = 400) or standard IPV (n = 400) at age 2, 4 and 6 months. In the booster trial, subjects received a single dose of IPV-Al at age 15–18 months. The primary endpoint was type-specific seroconversion, defined as an antibody titre ≥4-fold higher than the estimated maternal antibody titre and a titre ≥8, one month after the primary vaccination series. In the booster trial, the primary endpoint was the type-specific booster effects (geometric mean titre (GMT) post-booster (Day 28)/GMT pre-booster (Day 0).ResultsSeroconversion rates following primary vaccination with IPV-Al vs IPV were: 96.1% vs 100% (type 1); 100% vs 100% (type 2); and 99.2% vs 100% (type 3) respectively. IPV-Al was non-inferior to IPV, as the lower 95% confidence limits of the treatment differences were above the pre-defined −10%-point limit: 3.94% (-6.51; −2.01) for type 1; 0.0% (-1.30; −1.37) for type 2; −0.85 (-2.46; 0.40) for type 3. The booster effects for the group primed with IPV-Al versus the group primed with IPV were 25.3 vs 9.2 (type 1), 19.1 vs 6.5 (type 2) and 50.4 vs 12.5 (type 3). IPV-Al had a comparable safety profile to that of IPV.ConclusionsNon-inferiority of IPV-Al to standard IPV with respect to seroconversion after vaccination at 2, 4 and 6 months was confirmed for all three poliovirus serotypes. A robust booster response was demonstrated following vaccination with IPV-Al, regardless of the primary vaccine received. Both vaccines were well tolerated.ClinicalTrials.gov identifiers: NCT03025750 and NCT03671616.Funding: Bill & Melinda Gates Foundation.     

Safety,immunogenicity and lot-to-lot consistency of a new Bivalent Oral Polio Vaccine (bOPV) in healthy Infants: Results of a Phase III,observer blind,randomized, controlled clinical study

BackgroundPoliomyelitis infection continues to be endemic in few countries despite rigorous efforts for eradication. A new Bivalent Oral Polio Vaccine (BBio bOPV) was tested in a Phase III Clinical study.MethodsAn observer blind, randomized, controlled clinical study was conducted comparing BBio bOPV with a licensed bOPV (SII bOPV). Initially in Part 1, 40 children 5–6 years of age were given a single dose of either vaccine in 1:1 ratio. In Part 2, 1080 infants of 6–8 weeks of age were received in 1:1:1:1 ratio one of the 3 lots of BBio bOPV or SII bOPV at 6, 10 and 14 weeks of age. Blood samples were collected to assess neutralizing antibody responses against Polio Type 1 and 3 viruses. Safety of the vaccines were recorded.ResultsAll children were seroprotected against both Type 1 and Type 3 polioviruses post-vaccination. More than 96% of the infants demonstrated seroconversion as well as seroprotection against both types of polioviruses. The geometric mean titres (GMT) for Type 1 and Type 3 antibodies were comparable between the groups. The 3 lots of BBio bOPV generated similar GMTs of Type 1 and Type 3 antibodies. In total 387 participants reported at least one adverse event and 18 serious adverse events. None of these events were vaccine related.ConclusionsThe new bOPV vaccine demonstrated immunogenicity that was non-inferior to a licensed bOPV vaccine. Consistency in immune response by 3 consecutively manufactured lots was also demonstrated. The vaccine did not cause any adverse event.Clinicaltrials.gov.identifier: NCT02766816.     

Evaluating cessation of the type 2 oral polio vaccine by modeling pre- and post-cessation detection rates

The globally synchronized removal of the attenuated Sabin type 2 strain from the oral polio vaccine (OPV) in April 2016 marked a major change in polio vaccination policy. This change will provide a significant reduction in the burden of vaccine-associated paralytic polio (VAPP), but may increase the risk of circulating vaccine-derived poliovirus (cVDPV2) outbreaks during the transition period. This risk can be monitored by tracking the disappearance of Sabin-like type 2 (SL2) using data from the polio surveillance system. We studied SL2 prevalence in 17 countries in Africa and Asia, from 2010 to 2016 using acute flaccid paralysis surveillance data. We modeled the peak and decay of SL2 prevalence following mass vaccination events using a beta-binomial model for the detection rate, and a Ricker function for the temporal dependence. We found type 2 circulated the longest of all serotypes after a vaccination campaign, but that SL2 prevalence returned to baseline levels in approximately 50 days. Post-cessation model predictions identified 19 anomalous SL2 detections outside of model predictions in Afghanistan, India, Nigeria, Pakistan, and western Africa. Our models established benchmarks for the duration of SL2 detection after OPV2 cessation. As predicted, SL2 detection rates have plummeted, except in Nigeria where OPV2 use continued for some time in response to recent cVDPV2 detections. However, the anomalous SL2 detections suggest specific areas that merit enhanced monitoring for signs of cVDPV2 outbreaks.     

Polio eradication in India: Progress,but environmental surveillance and vigilance still needed

Poliomyelitis has appeared in epidemic form, become endemic on a global scale, and has been reduced to near elimination, all within the span of documented medical history.     

How is walking speed related to muscle strength? A study of healthy persons and persons with late effects of polio

OBJECTIVES: To evaluate the relationship between walking speed and muscle strength in the lower extremities in healthy persons and in persons with late effects of polio and to compare the models for these relationships. DESIGN: Retrospective analysis. SETTING: University hospital department. PARTICIPANTS: An urban sample of 144 healthy men and women (age range, 40-79 y) and 234 (146 women, 88 men) subjects with late polio. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Muscle strength in the lower extremities was measured and combined into an index. Walking speed for spontaneous and maximal walking was measured. A nonlinear regression model was developed. RESULTS: Evidence was provided for the nonlinear relationship between walking speed and strength. A specific strength threshold could not be identified. The asymptote of this curve for maximal walking was 2.57 m/s in the healthy group and 2.02 m/s in the subjects with late effects of polio. A high body mass index (>25 kg/m2) lowered the asymptote. CONCLUSIONS: It is important to prevent strength decrease that approaches the critical level where a further reduction affects walking speed more evidently. The difference in the relationship between muscle strength and walking speed for the 2 groups studied may partly depend on biomechanic imbalance between muscle groups.     

Managing population immunity to reduce or eliminate the risks of circulation following the importation of polioviruses

Poliovirus importations into polio-free countries represent a major concern during the final phases of global eradication of wild polioviruses (WPVs). We extend dynamic transmission models to demonstrate the dynamics of population immunity out through 2020 for three countries that only used inactivated poliovirus vaccine (IPV) for routine immunization: the US, Israel, and The Netherlands. For each country, we explore the vulnerability to re-established transmission following an importation for each poliovirus serotype, including the impact of immunization choices following the serotype 1 WPV importation that occurred in 2013 in Israel. As population immunity declines below the threshold required to prevent transmission, countries become at risk for re-established transmission. Although importations represent stochastic events that countries cannot fully control because people cross borders and polioviruses mainly cause asymptomatic infections, countries can ensure that any importations die out. Our results suggest that the general US population will remain above the threshold for transmission through 2020. In contrast, Israel became vulnerable to re-established transmission of importations of live polioviruses by the late 2000s. In Israel, the recent WPV importation and outbreak response use of bivalent oral poliovirus vaccine (bOPV) eliminated the vulnerability to an importation of poliovirus serotypes 1 and 3 for several years, but not serotype 2. The Netherlands experienced a serotype 1 WPV outbreak in 1992–1993 and became vulnerable to re-established transmission in religious communities with low vaccine acceptance around the year 2000, although the general population remains well-protected from widespread transmission. All countries should invest in active management of population immunity to avoid the potential circulation of imported live polioviruses. IPV-using countries may wish to consider prevention opportunities and/or ensure preparedness for response. Countries currently using a sequential IPV/OPV schedule should continue to use all licensed OPV serotypes until global OPV cessation to minimize vulnerability to circulation of imported polioviruses.