Presence of lysine at aa 335 of the hemagglutinin-neuraminidase protein of mumps virus vaccine strain Urabe AM9 is not a requirement for neurovirulence

The recent global resurgence of mumps has drawn attention to the continued need for robust mumps immunization programs. Unfortunately, some vaccines derived from inadequately attenuated vaccine strains of mumps virus have caused meningitis in vaccinees, leading to withdrawal of certain vaccine strains from the market, public resistance to vaccination, or in some cases, cessation of national mumps vaccination programs. The most widely implicated mumps vaccine in cases of postvaccination meningitis is derived from the Urabe AM9 strain, which remains in use in some countries. The Urabe AM9 vaccine virus has been shown to exhibit a considerable degree of nucleotide and amino acid heterogeneity. Some studies have specifically implicated variants containing a lysine residue at amino acid position 335 in the hemagglutinin-neuraminidase (HN) protein with neurotoxicity, whereas a glutamic acid residue at this position was associated with attenuation. To test this hypothesis we generated two modified Urabe AM9 cDNA clones coding either for a lysine or a glutamic acid at position 335 in the HN gene. The two viruses were rescued by reverse genetics and characterized in vitro and in vivo. Both viruses exhibited similar growth kinetics in neuronal and non-neuronal cell lines and were of similar neurotoxicity when tested in rats, suggesting that amino acid 335 is not a crucial determinant of Urabe AM9 growth or neurovirulence.     

流行性腮腺炎流行病学调查分析与控制对策

目的分析新兴县流行性腮腺炎的流行病学特点，以提供防治参考。方法运用描述性流行病学的统计方法对新兴县2008年报告的腮腺炎病例进行分析。结果新兴县2008年1月至12月共报告流行性腮腺炎23例，年报告发病率为4.98／10万，病例主要集中在流动人口较多的新城镇、太平镇等地区，6月为高发月份，占总发病数26.08％，发病人群主要是10-15岁小学生，占60.86％，腮腺炎相关疫苗免疫史空白和免疫史不详占73.73％。结论加强儿童腮腺炎疫苗的接种工作，重点是流动儿童，发生疫情及时采取综合措施，是控制流行性腮腺炎疫情的重要手段。     

Long-term survivors following autologous haematopoetic stem cell transplantation have significant defects in their humoral immunity against vaccine preventable diseases,years on from transplant

Current international guidelines recommend routinely vaccinating haematopoetic stem cell transplant (HSCT) recipients. Despite significant infection-related mortality following autologous HSCT, routine vaccination programmes (RVP) completion is poor. For recovered HSCT recipients, it is uncertain whether catch-up vaccination remains worthwhile years later.To determine potential susceptibility to vaccine preventable infections, we measured antibody titres in 56 patients, a median of 7 years (range 0–29) following autologous HSCT, who had not completed RVP. We found that almost all participants had inadequate titres against diphtheria (98.2%) and pneumococcal infection (100%), and a significant proportion had inadequate titres against measles (34.5%). Of those subsequently vaccinated according to available guidelines, many mounted adequate serological responses.These data suggest a pragmatic catch-up approach for autologous HSCT recipients who have not completed RVP is advisable, with universal vaccination against some pathogens (e.g. Streptococcus pneumoniae and diphtheria) and serologically-guided approaches for others (e.g. measles and varicella zoster virus).     

Establishment of a model to assess mumps virus neurovirulence in neonatal Wistar rats

Mumps virus (MuV) is highly neurotropic and neurovirulent, hence, the neurovirulence of virus seeds used in the production of mumps vaccines must be tested. The previous neurovirulence evaluation method involves measuring the area of the cavity in the Lewis neonatal rat brain caused by MuV through paraffin sectioning and hematoxylin-eosin (HE) staining. However, the processes of paraffin sectioning and HE staining are time consuming and complicated. To solve this problem, in this study, a vibratome sectioning system was first deployed to evaluate MuV neurovirulence in the rat brain instead of paraffin sectioning and HE staining. The results showed that the vibratome sectioning method could assess the neurovirulence potential of MuV more objectively and efficiently. In addition, the effects of different MuV doses and the ages of the rats in days on this evaluation method were explored. The results indicate that MuV at no less than 10 50 % cell culture infective dose (CCID₅₀) could cause obvious cavity formation in 1-day-old rat brains. The neonatal rat model developed in this study could evaluate the neurovirulence of different MuV strains with high sensitivity and good repeatability.     

Cost-effectiveness analyses of monovalent mumps vaccination programs for Japanese children

BackgroundThe most common preventative measure against mumps is vaccination with mumps vaccine. Over 122 countries have implemented mumps vaccine routine immunization programs, mostly via Measles-Mumps-Rubella (MMR) vaccine. In Japan, the unexpectedly high incidence of aseptic meningitis caused by mumps vaccine led to the discontinuation of the MMR national vaccination program in 1993, inadvertently resulting in the re-emergence of mumps. Plans of introducing monovalent mumps vaccine into routine vaccination schedule have become one of the emerging topics in health policy that has warranted the need in evaluating its value for money.MethodsWe conducted cost-effectiveness analyses with Markov model and calculated incremental cost-effectiveness ratios (ICERs) of two different vaccination programs (a single-dose program at one-year-old, a two-dose program with second dose uptakes at five) compared to status quo from both payers’ and societal perspectives. Transition probabilities and utility weights in estimating quality-adjusted life-year (QALY), and disease treatment costs were either estimated or obtained from literature. Costs per vaccination were assumed at ¥6140 (US$58;1US$ = ¥106).ResultsBoth programs reduce disease treatment costs compared to status quo, while the reduction cannot offset vaccination cost. ICER of either program is found to be under ¥5,000,000 (US$47,170)/QALY willingness-to-pay (WTP) threshold from either perspective. Results of probabilistic sensitivity analyses expressed by net monetary benefit indicated that at the WTP threshold, the acceptability is at 92.6% for two-dose vaccination program, 0% for single-dose vaccination program, and 7.4% for current no vaccination program. Two-dose program was optimal among the alternatives. One-way sensitivity analyses revealed that proportion of mumps-related hearing loss among mumps cases and vaccine effectiveness (VE) were key variables in changing the ICERs.ConclusionRoutine vaccination program of single- and two-dose programs were cost-effective from both payers’ and societal perspectives. Between the two, the two-dose vaccination program was observed to be more favorable.     

Mumps interstitial nephritis: a case report

Mumps is still a common childhood disease in rural areas where mumps vaccination is not widespread. A 14-year-old girl with fatal interstitial nephritis as a complication of mumps is reported. The patient had not been vaccinated with mumps vaccine and had contracted mumps during a village epidemic. The illness began with parotitis, and renal insufficiency developed within a week. The patient’s renal function rapidly deteriorated and the outcome was fatal. The postmortem renal necropsy sample demonstrated interstitial mononuclear cell infiltration, edema, and focal tubular epithelial cell damage, confirming the clinical diagnosis. In developing countries routine mumps vaccination may help to prevent possible fatal complications of mumps. Furthermore, patients with mumps, especially complicated cases, should be followed closely. Received: 19 August 1998 / Revised: 7 December 1998 / Accepted: 8 December 1998     

状态空间模型在流行性腮腺炎防控评价中的应用

目的 分析2012年和2014年流行性腮腺炎（腮腺炎）流行特征，探讨山东省2剂次含腮腺炎成分疫苗（MuCV）接种的预防效果。方法 在一定模型假定基础上，结合相关文献设置合理参数，构建状态空间模型，利用迭代滤波对模型进行参数估计。结果 2012年和2014年托幼及学生人群基础再生数（R₀）分别为4.49（95%CI：4.30~4.67）和2.50（95%CI：2.38~2.61）。结论 状态空间模型能够很好地描述腮腺炎传播过程；山东省实行2剂MuCV能够有效降低腮腺炎在人群中的传播；托幼和学生是实现腮腺炎进一步控制的重要人群，应进一步提高2剂次MuCV接种率。     

优质护理对小儿流行性腮腺炎治疗的作用

目的探究优质护理对小儿流行性腮腺炎治疗的作用。方法在2010年6月~2013年6月我院收治了100例流行性腮腺炎患儿,并通过抽签法将100例患儿分为研究组和参照组,每组各50例患儿,其中对研究组患儿在进行常规护理的同时进行优质护理,对参照组患儿进行常规护理,对两组患儿的恢复情况进行分析。结果对研究组和参照组的患儿进行不同的护理,可以看出研究组的患儿病情的恢复情况比参照组患儿的情况要明显,因此(P0.05)具有统计学意义。结论优质的护理对于小儿流行性腮腺炎治疗起到了积极的作用,不仅有效的治愈了患儿的疾病,也使得家长更加安心,值得临床推广。     

Cross-neutralization between vaccine and circulating wild-type mumps viruses in Korea

Mumps is a contagious disease caused by the mumps virus. It can be prevented using mumps vaccines, administered as a measles-mumps-rubella (MMR) vaccine. For first and second dose immunization, children aged 12–15 months and 4–6 years have been administered this vaccine since 1997 in Korea. Nevertheless, mumps outbreaks still occur in vaccinated populations worldwide. Hence, immunity against these diseases may be attenuated, or there are antigenic differences between currently available vaccine strains and circulating wild-type viruses. After the introduction of national immunization programs in Korea, mumps cases became sporadic. Viral genotypes F, H, and I have emerged since 1998 whereas the vaccine strains belong to genotype A. Here, we compared the amino acid sequences of the haemagglutinin-neuraminidase (HN) gene from wild-type viruses and the mumps vaccine and measured the cross-neutralization titers between them. We selected the F, H, and I wild-type mumps strains circulating in Korea from 1998 to 2016 and analyzed changes in the amino acid sequence of the protein encoded by the HN gene. We measured mumps virus-specific IgG and rapid focus reduction neutralization test (FRNT) titers in Korean isolates and sera obtained from 50 children aged 1–2 years who had been administered a single dose of MMR vaccine. Analysis of the HN protein sequences disclosed no changes in the glycosylation sites but did reveal 4–5 differences between the Korean isolates and the genotype A vaccine strain in terms of the neutralizing epitope sites on their HN proteins. Post-vaccination FRNT titers were significantly lower against genotypes F, H, and I than they were against genotype A. This finding highlights the possibility of a recurrence of mumps outbreaks in vaccinated populations depending on the degree of genetic conservation of the HN gene. Further research into this issue is needed to prevent the resurgence of mumps.     

Mumps Hoshino and Torii vaccine strains were distinguished from circulating wild strains

Aseptic meningitis and acute parotitis have been observed after mumps vaccination. Mumps outbreaks have been reported in Japan because of low vaccine coverage, and molecular differentiation is required to determine whether these cases are vaccine associated. RT-nested PCR was performed in the small hydrophobic gene region, and viruses were differentiated by restriction fragment length polymorphism assay. A total of 584 nucleotides were amplified. The PCR product of the Hoshino strain was cut into two fragments (313 and 271 nucleotides) by MfeI; that of the Torii strain was digested with EcoT22I, resulting in 332- and 252-nucleotide fragments. Both strains were genotype B and had an XbaI site, resulting in two fragments: 299 and 285 nucleotides. Current circulating wild types were cut only by XbaI or MfeI. However, the MfeI site of the wild types was different from that of the Hoshino strain, resulting in 451- and 133-nucleotide fragments. Using three restriction enzymes, two mumps vaccine strains were distinguished from wild types, and this separation was applied to the identification of vaccine-related adverse events.