2020年南宁市流行性腮腺炎ARIMA模型预测研究

目的 建立自回归移动平均模型(auto-regressive integrated moving average,ARIMA)预测南宁市流行性腮腺炎的发病率,为防控流行性腮腺炎提供理论依据. 方法 采用SPSS 23.0软件,使用南宁市2013年1月-2019年6月流行性腮腺炎月发病率建立ARIMA模型,运用2019年...     

杭州市流行性腮腺炎疫苗前时代人群抗体水平调查

为了解流行性腮腺炎（腮腺炎）疫苗前时代杭州城乡人群免疫状况,为制订免疫方案提供依据,并积累本底资料,于1995年对城乡＜50岁的927人进行了腮腺炎血凝抑制（HI）抗体调查．结果：HI抗体阳性率为55．77％,几何平均滴度倒数（GMRT）为3．06±3.61;城区HI抗体阳性率和GMRT分别为56．65％和3．11±3.75,乡村分别为54.61％和2.99±3．44;男性分别为54.55％和2．94±3．51,女性分别为57．05％和3.19±3．72;城乡或男女HI抗体阳性率和GMRT的差异均无显著的统计学意义。人群HI抗体阳性率随年龄增长先升后降,＜5.5～9、10～14、15～19、20～29、30～39、40～49岁组的HI抗体阳性率分别为22．28％、53．30％、75．17％、75．86％、61.60％、62．71％、65．75％,其差异有非常显著的统计学意义（x2=132．15,p＜0.01）．结果提示：10岁以下儿童,特别是1～4岁儿童是预防腮腺炎的重点保护对象．     

A highly efficacious live attenuated mumps virus–based SARS-CoV-2 vaccine candidate expressing a six-proline stabilized prefusion spike

With the rapid increase in SARS-CoV-2 cases in children, a safe and effective vaccine for this population is urgently needed. The MMR (measles/mumps/rubella) vaccine has been one of the safest and most effective human vaccines used in infants and children since the 1960s. Here, we developed live attenuated recombinant mumps virus (rMuV)–based SARS-CoV-2 vaccine candidates using the MuV Jeryl Lynn (JL2) vaccine strain backbone. The soluble prefusion SARS-CoV-2 spike protein (preS) gene, stablized by two prolines (preS-2P) or six prolines (preS-6P), was inserted into the MuV genome at the P–M or F–SH gene junctions in the MuV genome. preS-6P was more efficiently expressed than preS-2P, and preS-6P expression from the P–M gene junction was more efficient than from the F–SH gene junction. In mice, the rMuV-preS-6P vaccine was more immunogenic than the rMuV-preS-2P vaccine, eliciting stronger neutralizing antibodies and mucosal immunity. Sera raised in response to the rMuV-preS-6P vaccine neutralized SARS-CoV-2 variants of concern, including the Delta variant equivalently. Intranasal and/or subcutaneous immunization of IFNAR1^−/− mice and golden Syrian hamsters with the rMuV-preS-6P vaccine induced high levels of neutralizing antibodies, mucosal immunoglobulin A antibody, and T cell immune responses, and were completely protected from challenge by both SARS-CoV-2 USA-WA1/2020 and Delta variants. Therefore, rMuV-preS-6P is a highly promising COVID-19 vaccine candidate, warranting further development as a tetravalent MMR vaccine, which may include protection against SARS-CoV-2.

The current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused tremendous damage to all aspects of our society (1–3). As of 1 June 2022, nearly 528 million cases have been reported worldwide, with nearly 6.3 million deaths (∼1.20% mortality). Symptoms of SARS-CoV-2 infection are primarily respiratory although increasing numbers of other syndromes such as cognitive deficits are being reported. As of June 2022, several SARS-CoV-2 vaccines based on messenger RNA (mRNA), inactivated virus, and adenovirus vectors (Ad26.COV2.S and ChAdOx1) have been approved for vaccination in humans over the age of 5 (4). These vaccines are highly efficacious, reaching 70 to 95% effectiveness against SARS-CoV-2 infection (4).Despite the high success of the current SARS-CoV-2 vaccines, there are several limitations. Protection provided by current vaccines begins to decline after 3 mo (5), which has required a third or fourth dose to boost the immune response. Current vaccines are less effective against recently emergent SARS-CoV-2 variants of concern (VoCs) (6–9). More and more evidence has shown that vaccine-induced neutralizing antibodies were significantly weakened or insufficient to neutralize VoCs such as the Delta variant (7–9), which spreads much faster and causes more severe illness than the earlier strains. In addition, the current vaccines neutralize the most recently emerged variant, Omicron, ∼40 times less efficiently compared with early SARS-CoV-2 isolates (10, 11). The mRNA vaccines are expensive to produce, hard to transport internationally, and difficult to store in many countries because of the requirement for expensive −80 °C freezers.A safe and efficacious pediatric SARS-CoV-2 vaccine is needed to halt the current pandemic. Pfizer’s mRNA vaccine is 90.7% effective in preventing COVID-19 symptoms in children 5 to 11 y old (12, 13). On 17 June 2022, Food and Drug Administration (FDA) authorized emergency use of the Moderna and Pfizer mRNA vaccines for children down to 6 mo of age. As of 23 June 2022, a total of 13.7 million COVID-19 cases have occurred in children, representing 18.8% of the total COVID-19 cases in the United States. Notably, COVID-19 cases in children have increased significantly after the reopening of schools. Therefore, development of other vaccine platforms and strategies to enhance durability, reduce cost, and enhance stability are essential for terminating the pandemic.Historically, the MMR (measles/mumps/rubella) vaccine has been one of the safest and most effective human vaccines ever developed (14–16). The application in children started in the 1960s and provides long-lasting protection against these three viruses (14, 16). Among the three MMR components, measles virus (MeV) and mumps virus (MuV) are nonsegmented negative-sense (NNS) RNA viruses, belonging to the family Paramyxoviridae in the order Mononegavirales. The MuV genome is 15,384 nt in length, and it encodes seven structural proteins arranged in the order 3′-leader-N-P-M-F-SH-HN-L-trailer-5′ (17). The limited number of discrete genes of the NNS RNA genome and the intergenic regions available for inserting additional genes facilitates the development of live vectored vaccines. MuV is an excellent viral vector for delivery of vaccines against other highly pathogenic viruses, primarily because of its high safety and efficacy, well-established good manufacturing practices, induction of long-lived immunity, and the potential for the development of a quadrivalent vaccine against four major pediatric diseases (18, 19).In this study, we developed a suite of safe and highly efficacious recombinant MuV (rMuV)–based SARS-CoV-2 vaccine candidates expressing a stabilized prefusion spike with two prolines (preS-2P) or six prolines (preS-6P) at different gene junctions in the MuV genome. Among them, the rMuV-based preS-6P vaccine induces a broad neutralizing antibody against VoCs and T cell immunity, and provides complete protection against SARS-CoV-2 WA1 and the Delta variant challenge in animal models.     

French national diagnostic and care protocol for Kawasaki disease

Kawasaki disease (KD) is an acute vasculitis with a particular tropism for the coronary arteries. KD mainly affects male children between 6 months and 5 years of age. The diagnosis is clinical, based on the international American Heart Association criteria. It should be systematically considered in children with a fever, either of 5 days or more, or of 3 days if all other criteria are present. It is important to note that most children present with marked irritability and may have digestive signs. Although the biological inflammatory response is not specific, it is of great value for the diagnosis. Because of the difficulty of recognising incomplete or atypical forms of KD, and the need for urgent treatment, the child should be referred to a paediatric hospital as soon as the diagnosis is suspected. In the event of signs of heart failure (pallor, tachycardia, polypnea, sweating, hepatomegaly, unstable blood pressure), medical transfer to an intensive care unit (ICU) is essential. The standard treatment is an infusion of IVIG combined with aspirin (before 10 days of fever, and for a minimum of 6 weeks), which reduces the risk of coronary aneurysms. In case of coronary involvement, antiplatelet therapy can be maintained for life. In case of a giant aneurysm, anticoagulant treatment is added to the antiplatelet agent. The prognosis of KD is generally good and most children recover without sequelae. The prognosis in children with initial coronary involvement depends on the progression of the cardiac anomalies, which are monitored during careful specialised cardiological follow-up.     

Long-term immunoprotection after live attenuated measles-mumps-rubella booster vaccination in children with juvenile idiopathic arthritis

IntroductionVaccines, especially live attenuated vaccines, in children with JIA pose a great challenge due to both potential lower immunogenicity and safety as a result of immunosuppressive treatment. For many years, in the Netherlands, JIA patients receive a measles-mumps-rubella (MMR) booster vaccine at the age of nine years as part of the national immunization program.ObjectivesTo study long-term humoral immunoprotection in a large cohort of JIA patients who received the MMR booster vaccine while being treated with immunomodulatory therapies at the Wilhelmina Children’s Hospital in Utrecht, the Netherlands.MethodsMMR-specific IgG antibody concentrations in stored serum samples of vaccinated JIA patients were determined with chemiluminescent microparticle immunoassays (CMIA). Samples were analyzed five years after MMR booster vaccination and at last available follow-up visit using both crude and adjusted analyses. Additional clinical data were collected from electronic medical records.ResultsIn total, 236 samples from 182 patients were analyzed, including 67 samples that were available five years post-vaccination, and an additional 169 samples available from last visits with a median duration after vaccination of 6.9 years (IQR: 2.8–8.8). Twenty-eight patients were using biologic disease-modifying antirheumatic drugs (bDMARDS) of whom 96% anti-TNF agents and 4% tocilizumab. Percentages of protective antibody levels against measles after five years were significantly lower for patients who used bDMARD therapy at vaccination compared to patients who did not: 60% versus 86% (P = 0.03). For mumps (80% versus 94%) and rubella (60% versus 83%) this difference did not reach statistical significance (P = 0.11 and P = 0.07, respectively). Antibody levels post-vaccination decreased over time, albeit not significantly different between bDMARD users and non-bDMARD users.ConclusionThe MMR booster vaccine demonstrated long-term immunogenicity in the majority of children with JIA from a large cohort, although lower percentages of protective measles antibody levels were observed in bDMARD users. Hence, it might be indicated to measure antibody levels at least five years after MMR booster vaccination in the latter group and advice an extra booster accordingly.     

基于优劣解距离法、秩和比法和线性插值法的我国儿童保健工作质量综合评价

目的：运用优劣解距离法（TOPSIS法）、秩和比法及线性插值法对2020年全国31个省（区、市）儿童保健工作质量进行综合评价，对比分析3种方法对儿童保健工作质量评价的应用价值，为制定儿童健康发展规划提供参考依据。方法：收集2021年《中国卫生健康统计年鉴》中，全国31个省（区、市）的低出生体重率（%）、围产儿死亡率（‰）、5岁以下儿童低体重患病率（%）等6项反映儿童保健工作质量的常见指标，运用TOPSIS法、秩和比法和线性插值法分别对全国31个省（区、市）的儿童保健工作质量进行评价，采用Spearman相对系数法对3种评价方法的排序结果进行相关性分析。结果：相关性分析结果表明，3种方法的评价结果具有高度的正相关关系，其中，秩和比法和线性插值法排序结果的一致性最好（R=0.968,P<0.01），其次是TOPSIS法和秩和比法（R=0.845,P<0.01），第三是TOPSIS法和线性插值法（R=0.832,P<0.01）。虽然3种方法的评价结果具有高度的正相关关系，但是其评价结果仍有一定的差别。对3种方法评价结果进行综合排序，2020年儿童保健工作质量排名居前3位的省...     

Common issues and improvement solution of vaccine hesitancy in children with underlying neurological conditions: Experience from one National Children’s Medical Center in China

BackgroundParents and healthcare providers usually defer or avoid immunization for children with neurological conditions. This study was conducted to investigate the common issues of immunization among these special children and the impact of specialists’ recommendation on improving immunization practice.MethodWe included 2,221 children with underlying neurological conditions seeking vaccination consultation at the first Immunization Advisory Clinic in China during 2017–2019. The primary neurological conditions and immunization status were analyzed. All parents were informed to self-report the adverse events following catch-up immunization. For specially concerned children with hereditary disorders, immune-related encephalopathy and epilepsy, we conducted the active follow-up to monitor the compliance with recommendation and the adverse events.ResultAll counselling children were assessed as not having any contraindication of immunization. A total of 2,019 (90.9%) children with underlying neurological conditions had delayed immunization and 99 (4.5%) had non-immunization. The coverage rate of age-appropriate vaccines was 56.1%. The most concerned vaccines were diphtheria, tetanus and acellular pertussis combined vaccine, diphtheria and tetanus combined vaccine, meningococcal polysaccharide vaccine and Japanese encephalitis vaccine. Resuming immunization was recommended for the 2,048 (92.2%) children. Most of counselling children complied with the specialists’ recommendation. Neither progress nor flaring of the neurological medical conditions was reported from parents.ConclusionVaccine hesitancy was a common issue for Chinese children with all kinds of neurological conditions. Specialized consultation on immunization is helpful to build vaccine confidence for the special children. Immunization for children with underlying neurological conditions is generally safe.     

Safety,tolerability, and immunogenicity of V114 pneumococcal vaccine compared with PCV13 in a 2+1 regimen in healthy infants: A phase III study (PNEU-PED-EU-2)

BackgroundThis phase III study evaluated safety, tolerability, and immunogenicity of V114 (15-valent pneumococcal conjugate vaccine) in healthy infants. V114 contains all 13 serotypes in PCV13 and additional serotypes 22F and 33F.MethodsHealthy infants were randomized to two primary doses and one toddler dose (2+1 regimen) of V114 or PCV13 at 3, 5, and 12 months of age; diphtheria, tetanus, pertussis (DTaP), inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib), hepatitis B (HepB) vaccine was administered concomitantly. Adverse events (AEs) were collected on Days 1–14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-primary series, immediately prior to toddler dose, and 30 days post-toddler dose. Primary objectives included non-inferiority of V114 to PCV13 for 13 shared serotypes and superiority of V114 to PCV13 for serotypes 22F and 33F.Results1191 healthy infants were randomized to V114 (n = 595) or PCV13 (n = 596). Proportions of participants with solicited AEs and serious AEs were comparable between groups. V114 met non-inferiority criteria for 13 shared serotypes, based on difference in proportions with serotype-specific IgG ≥0.35 μg/mL (lower bound of two-sided 95% confidence interval [CI] >−10.0) and IgG geometric mean concentration (GMC) ratios (lower bound of two-sided 95% CI >0.5) at 30 days post-toddler dose. V114 met superiority criteria for serotypes 22F and 33F, based on response rates (lower bound of two-sided 95% CI >10.0) and IgG GMC ratios (lower bound of two-sided 95% CI >2.0) at 30 days post-toddler dose.Antibody responses to DTaP-IPV-Hib-HepB met non-inferiority criteria, based on antigen-specific response rates.ConclusionA two-dose primary series plus toddler dose of V114 was well-tolerated in healthy infants. Compared with PCV13, V114 provided non-inferior immune responses to 13 shared serotypes and superior immune responses to additional serotypes 22F and 33F.     

Use of live viral vaccines after HCT: Still a lot to learn

Revaccination program after HCT is necessary due to the loss of lifelong immunity acquired by previous vaccination or infections. The program is complex and even in a favourable scenario, it takes more than 2 years to be completed. As the complexity of HCT increases (alternative donors, diversity of monoclonal antibodies), studies evaluating the response to vaccination in this population are welcome, especially those that evaluate live attenuated vaccines given their scarcity. Furthermore, measles, mumps, rubella and even yellow fever, and poliomyelitis outbreaks have perplexed infectious diseases clinicians and epidemiologists globally, most of them due to the decline in vaccination coverage rates in children and adults, because of the growth of antivaccine movements around the world. The study of Lin et al. adds important information about measles, mumps and rubella vaccination after HCT.