Enhancing global vaccine pharmacovigilance: Proof-of-concept study on aseptic meningitis and immune thrombocytopenic purpura following measles-mumps containing vaccination

New vaccines designed to prevent diseases endemic in low and middle-income countries (LMICs) are now being introduced without prior record of utilization in countries with robust pharmacovigilance systems. To address this deficit, our objective was to demonstrate feasibility of an international hospital-based network for the assessment of potential epidemiological associations between serious and rare adverse events and vaccines in any setting. This was done through a proof-of-concept evaluation of the risk of immune thrombocytopenic purpura (ITP) and aseptic meningitis (AM) following administration of the first dose of measles-mumps-containing vaccines using the self-controlled risk interval method in the primary analysis. The World Health Organization (WHO) selected 26 sentinel sites (49 hospitals) distributed in 16 countries of the six WHO regions. Incidence rate ratios (IRR) of 5.0 (95% CI: 2.5–9.7) for ITP following first dose of measles-containing vaccinations, and of 10.9 (95% CI: 4.2–27.8) for AM following mumps-containing vaccinations were found. The strain-specific analyses showed significantly elevated ITP risk for measles vaccines containing Schwarz (IRR: 20.7; 95% CI: 2.7–157.6), Edmonston-Zagreb (IRR: 11.1; 95% CI: 1.4–90.3), and Enders’Edmonston (IRR: 8.5; 95% CI: 1.9–38.1) strains. A significantly elevated AM risk for vaccines containing the Leningrad-Zagreb mumps strain (IRR: 10.8; 95% CI: 1.3–87.4) was also found. This proof-of-concept study has shown, for the first time, that an international hospital-based network for the investigation of rare vaccine adverse events, using common standardized procedures and with high participation of LMICs, is feasible, can produce reliable results, and has the potential to characterize differences in risk between vaccine strains. The completion of this network by adding large reference hospitals, particularly from tropical countries, and the systematic WHO-led implementation of this approach, should permit the rapid post-marketing evaluation of safety signals for serious and rare adverse events for new and existing vaccines in all settings, including LMICs.     

麻疹-流行性腮腺炎-流行性乙型脑炎联合减毒活疫苗的稳定性研究

目的考察麻疹-流行性腮腺炎（流腮）-流行性乙型脑炎（乙脑）联合减毒活疫苗（Measles,Mumps and Japanese Encephalitis Combined Attenuated Live Vaccine;M-M-JEV）的稳定性。方法将M-M-JEV,37℃放置7d,检测病毒滴度;2-8℃放置0-25个月,检测外观、水分、病毒滴度、安全试验、异常毒性,0月和18个月时进行全检;（-30±2）℃放置0-30个月,检测外观、水分、病毒滴度、安全试验、异常毒性,0月、18个月、30个月时进行全检。结果所有检测结果,均符合2010年版《中华人民共和国药典》三部麻疹减毒活疫苗、流腮减毒活疫苗和乙脑减毒活疫苗的质量标准。结论 M-M-JEV有较好的稳定性。     

The weight of MMRV-related febrile convulsions among other clinical factors contributing to febrile convulsions in children

Background

It was previously demonstrated that MMRV vaccine causes a higher rate of febrile convulsions (FC) compared to the MMR vaccine. Additional risk factors for FC include age, familial tendency, day care attendance, viral diseases, complications at birth and developmental delay.

Objective

We evaluated the relative and attributable risk of FC for vaccinees’ age, ethnicity, low birth weight, preterm birth and MMRV vaccination in 10–24 months old children.

Methods

Data on medical history and vaccination were extracted from data warehouses of Clalit Health Services and Israel's Ministry of Health and linked on an individual record level for 90,294 MMR- and 8344 MMRV-vaccinees. A retrospective study design was used to reveal the risk factors associated with FC in study participants.

Results

During the second week after immunization, an elevated relative risk of FC was demonstrated in MMRV-recipients (adjusted RR = 2.16 (95%CI: 1.01; 4.64)). However, the cumulative incidence of FC during the entire 40-day observation period did not differ between the MMR and MMRV vaccinees. The MMRV-specific attributable risk of FC was not statistically significant at any point of observation period and was exceedingly low compared to other risk factors, equaling 5.3 FC cases per 10,000 vaccinees (95%CI: −1.4; 12.2).

Discussion

Our findings demonstrate that MMRV-associated FC in 10–24 months old contributes very marginally to the overall rate of FC in this population.

Conclusion

Given the low number of MMRV-specific FC cases, their transient nature and the benefit of vaccination, the overall benefit-risk of the vaccine can be considered favourable. Nonetheless, the option of separate immunization with MMR + V should be offered to parents, in order to maintain sufficient vaccine uptake in the population.     

2008 - 2012 年成都市温江区流行性腮腺炎疫情分析

目的了解成都市温江区流行性腮腺炎（流腮）的流行特点和趋势,为制定流腮预防控制策略提供依据。、方法采用描述流行病学方法对2008—2012年温江区流腮监测资料和2008年温江区流腮疫苗接种资料进行统计分析。结果2008—2012年温江区流腮报告病例为1097例,2008年发病率最高为137．25／10万;2010年发病率最低为27．36／10万。2008年下半年开展3—16岁儿童流腮疫苗预防接种,应种27347人,实种23710人,接种率达86．70％。春末夏初为明显发病高峰季节,占总发病数的43．39％,其中5月发病最高占总发病数的15．77％。3—14岁年龄组占总发病数的81．13％,男性发病率高于女性（x2=83．06,P〈0．01）,学生、托幼儿童占总发病数的83．50％。城市及城乡结合地区占总发病数的84．32％高于农村。结论2008—2012年成都市温江区流腮发病重点单位是学校和托幼机构,建议适时开展流腮疫苗接种活动。     

2016—2021年厦门市流行性腮腺炎流行特征分析与趋势预测

目的 了解和掌握厦门市流行性腮腺炎的流行特征及变化趋势。方法 从国家传染病监测系统收集2016—2021年厦门市流行性腮腺炎的发病资料,计算并分析不同性别、年龄、时间的发病率变化情况;用年平均变化百分比(annual mean percentage change, APC)评价发病率变化趋势,用GM(1,1)模型预测未来三年发病率。结果2016—2021年厦门市共报告流行性腮腺炎2 332例,发病率在3.99/10万~13.60/10万之间波动,年平均发病率9.20/10万,男性(10.98/10万)高于女性(7.27/10万),发病年龄集中在1~14岁(1 976例,占84.73%),其中学生和幼托机构儿童1 727例。发病时间呈双高峰分布,发病例数最多在5月和11月。全市发病率年均下降21.61%(t=-3.49,P<0.05)。GM(1,1)模型建模预测值与实际值误差11.14%,预测2022—2024年发病率将进一步下降。结论 厦门市流行性腮腺炎发病率呈下降趋势,但仍处在福建省中上水平,应进一步加强疫苗接种和行为干预。     

一起小学流行性腮腺炎爆发的调查分析

目的核实疫情,确定某小学流行性腮腺炎（简称流腮）暴发的存在并描述疫情三间分布特征和流行强度,探讨发病危险因素。结论按照病例定义,开展病例搜索,描述其三间分布后,结合现场流行病学调查情况,形成假设,再采用病例对照研究方法验证假设。结果某小学2009年5月1日至6月18日搜索到符合病例定义的病例共33例。首例病例5月21日发病,6月14-17日出现发病高峰。二（3）班罹患率最高,为28%。男生罹患率为12%,女生罹患率为9%。病例对照研究表明,在校就餐是危险因素;吃午饭前洗手、平时洗手时使用肥皂是保护因素。结论根据病例临床表现、三间分布特征,确定某小学存在流行性腮腺炎暴发;建议校方减少学生在教室就餐的机会,加强宣传教育,提高学生自我保护意识,养成良好的洗手习惯。     

2005-2006年北京市东城区流行性腮腺炎发病的流行病学分析

目的 了解北京市东城区流行性腮腺炎(流腮)流行病学特征,为控制流行性腮腺炎提供科学依据.方法 利用流行性腮腺炎疫情资料,包括法定传染病报告系统和流腮监测系统流行病学个案调查及实验室监测资料,分析东城区流行性腮腺炎流行病学特征.结果 2005-2006年北京市东城区报告本地区流腮病例159例,年平均发病率11.28/10万.发病主要集中在5～15岁,占67.30%.学生发病占55.35%;3～5月发病占33.33%;有免疫史发病占50.31%.麻风腮疫苗免疫期限小于5年与免疫期限大于5年、无免疫史间差别显著.结论 提高麻风腮疫苗接种率的同时,适时地加强免疫是预防和控制流行性腮腺炎发生不可忽视的重要措施.     

Kinetics of antibody and memory B cell responses after MMR immunization in children and young adults

The persistence of antigen-specific memory B-cells (MBCs) in children and young adults long time after vaccination against measles, mumps and rubella (MMR) is not known. Here we have looked at the Swedish immunization program and examined children 1–10 years after the first MMR dose in early childhood, as well as young adults 7–18 years after the second dose of MMR. We show that Ab titers and MBCs against measles and rubella have different kinetics, indicating that the MBC pool and the corresponding Ab titers are regulated independently. These data fit well with other findings that continuous IgG secretion comes from long-lived plasma cells and not MBCs. We also demonstrate that individuals with low post-vaccination Ab titers might have an adequate MBC response. It remains to be shown if memory B-cells provide the same protection as specific antibodies, but our data is a valuable complement to the incomplete knowledge about correlates of protection after vaccination.     

仙人掌加蛋清外敷治疗流行性腮腺炎效果观察

目的观察仙人掌捣烂加蛋清外敷治疗流行性腮腺炎的疗效。方法将42例患者随机分成治疗组24例和对照组18例。治疗组采用仙人掌捣烂加蛋清外敷联合内科常规治疗，对照组单用内科常规治疗。观察治疗后两组患者治疗有效率。结果治疗组总有效率为95．8％，对照组为66．7％，两组比较，P〈0．05，差异具有统计学意义。结论采用仙人掌捣烂加蛋清外敷联合内科常规治疗流行性腮腺炎，优于单用内科常规治疗，值得临床推广应用。     

基于德尔菲法的《中医、中西医结合流行性腮腺炎诊疗指南》第二轮专家问卷调查方法和结果分析

采用德尔菲（Delphi）法，在第一轮专家问卷的基础上，编制《中医、中西医结合流行性腮腺炎诊疗指南》第二轮专家问卷，向全国30位专家发送问卷调查，回收有效问卷24份，从诊断、证型、治法、处方等方面进行统计分析。旨在建立科学、客观、系统的中医、中西医结合流行性腮腺炎诊疗指南。