A collaborative approach to investigating the risk of thrombocytopenic purpura after measles-mumps-rubella vaccination in England and Denmark

The assessment of rare adverse events following vaccination may not be possible within a single country due to an insufficiently large denominator population. In 2008 a European consortium (VAESCO) was funded to perform collaborative vaccine safety studies. To help assess the feasibility of multi-country collaboration England and Denmark, who have established vaccine safety research infrastructures, undertook to work to a common protocol and share results and data to estimate the risk of a known true adverse event, thrombocytopenic purpura (TP) following measles-mumps-rubella (MMR) vaccination. TP is a known rare reaction to MMR and therefore provided an opportunity to assess whether two countries would produce similar results when working collaboratively. Despite some initial problems with ensuring data were comparable, the two countries gave very similar estimates of the relative incidence in the 6 weeks after vaccination and a pooled relative incidence estimate of 2.13 (95% confidence interval 1.55-2.94) and attributable risk of 1 in 50,000 doses. Both countries used hospital admissions for TP and the analysis was performed using the self controlled case series method which is particularly suited to collaborative studies because of its implicit control for individual level confounding. The study therefore shows the potential for vaccine safety collaborations across Europe to detect true associations through use of common protocols and sharing of results or data.     

幽门螺杆菌根治在儿童免疫性血小板减少性紫癜中的治疗意义

目的 探讨幽门螺杆菌(Hp)根治在儿童免疫性血小板减少性紫癜(ITP)中的治疗意义.方法 选取于2016年4月至2017年2月到湖北民族学院附属民大医院就诊的伴Hp感染的80例ITP患儿,根据随机数表法,将所有患儿分为观察组和对照组,每组各40例.对照组接受糖皮质激素治疗;观察组在对照组的基础上进行Hp根治治疗.治疗一段时间后,对比分析两组患儿治疗前后的血流变学和血小板参数的水平变化,对比分析两组患儿的Hp根除率、临床疗效和一年内复发率.结果 治疗后,观察组患者的Hp感染情况明显低于对照组(χ2=6.14,P<0.05).治疗后,观察组患者总有效率为92.50%,明显高于对照组的55.00%,差异有统计学意义(χ2=23.10,P<0.05).观察组患者一年内总复发率为5.00%(2例),对照组患者一年内总复发率为36.67%(11例),观察组患者的一年内总复发率明显低于对照组,差异有统计学意义(χ2=7.44,P=0.01).治疗后,观察组的血小板明显高于对照组(t=6.46,P<0.05).观察组的血小板相关免疫球蛋白G、血小板分布宽度、大型血小板比例、血浆黏度、血小板凝集率、红细胞电泳时间、红细胞压积比、血沉水平明显低于对照组(t值分别为-16.54、-13.28、-16.79、-8.97、-6.51、-5.40、-2.94、-4.35,均P<0.05).结论 儿童ITP与Hp感染有关,根除Hp治疗能够有效提高儿童ITP的临床疗效,降低复发率.     

Vaccination associated thrombocytopenic purpura in children

Patients who presented with purpura and blood platelets <30x10(9)/l within 1 month after vaccination were collected from a population based material of 506 consecutive pediatric patients with newly diagnosed ITP. Of the 35 such patients, 24 had thrombocytopenia after MMR vaccination giving an estimated ITP risk of approximately 1 in 30,000 MMR inoculations. Symptoms of the 35 patients were nearly always acute. Thrombocytopenia disappeared within a month in 74% of the study patients and lasted longer than 6 months in only 10%. Bleeding episodes were uncommon during the follow-up period. We conclude that the incidence of symptomatic thrombocytopenia after vaccinations is much lower than that after respective natural infections and that the outcome in most cases is excellent.     

The effect of measles-mumps-rubella (MMR) immunization on the immune responses of previously immunized primary school children

Current policies for measles control call for administration of a second dose of vaccine to immunize those who failed to respond to the initial dose and to boost the responses of those with low levels of antibody. However, there has been concern expressed publicly that reimmunization may have adverse immunologic consequences. To determine the effects of reimmunization on immune responses, primary school children (N=38, mean age=6.14+/-0.35 years) with documented previous measles-mumps-rubella vaccine (MMR) immunization during infancy 4-5 years earlier were studied before and 1 month after receiving MMR as a part of routine reimmunization in Beer-Sheva, Israel. A substantial number of children were seronegative to measles (24%), mumps (34%) and rubella (44%). On reimmunization all seroconverted to mumps and rubella and all but one (92%) seroconverted to measles. The geometric mean titer of measles virus neutralizing antibody increased from 171 to 724 and the greatest increases occurred in those with the lowest pre-immunization titers. Moderate increases in levels of total IgM, IgG and IgE were detected in those with increases in antibody to measles virus. After reimmunization leukocyte counts decreased significantly from (5.8 x 10(6))+/-2.3 to (3.4 x 10(6))+/-0.7 ml(-1) (P=0.0001). The percentages of both CD4(+) and CD8(+) T cells decreased while the CD4:CD8 ratio remained unchanged. The percentage of CD56(+) natural killer (NK) cells increased from 5.2+/-2.7 to 7.2+/-2.8 (P=0.01). Functional assays showed improved lymphoproliferation in response to stimulation with phytohemagglutinin and tetanus toxoid and stable NK lytic activity. Therefore, reimmunization was accompanied by decreased leukocyte counts, but leukocyte function was unchanged or improved.     

免疫性血小板减少性紫癜合并幽门螺杆菌感染患儿免疫功能变化及治疗效果

目的分析免疫性血小板减少性紫癜合并幽门螺杆菌感染患者免疫功能的变化及治疗效果。方法选取某院2011年3月-2012年3月收治的80例血小板减少性紫癜患儿作为观察组,根据患儿是否感染幽门螺杆菌,分为感染亚组和未感染亚组;同时,选择同期80例健康儿童作为对照组,比较各组间淋巴细胞亚群测定结果、临床疗效以及复发率。结果观察组幽门螺杆菌阳性率为55.00%（44/80）,显著高于对照组的2.50%（2/80）,差异有统计学意义（χ2=12.48,P=0.008）。各组间CD4+、CD4+/CD8+以及CD19+T淋巴细胞比较,差异有统计学意义（均P＜0.05）;其中感染亚组患儿CD4+［（13.40±4.65）%］、CD4+/CD8+T淋巴细胞［（0.69±0.18）%］明显低于未感染亚组［分别为（28.56±3.82）%、（1.04±0.23）%］,而CD19+T淋巴细胞［（45.21±10.20）%］则明显高于未感染亚组［（22.05±2.23）%］;未感染亚组和感染亚组患儿CD4+、CD4+/CD8+T淋巴细胞明显低于对照组［分别为（40.20±3.42）%、（1.54±0.42）%］,而CD19+T淋巴细胞明显高于对照组［(11.02±2.89)%］。感染亚组和未感染亚组患儿治疗有效率分别为90.91%、91.67%,两组差异无统计学意义（P＞0.05）。感染亚组患儿经抗幽门螺杆菌感染治疗后血小板减少性紫癜复发率（20.45%）显著低于未感染亚组患儿（30.56%;χ2=6.396,P=0.038）。结论通过免疫功能检测,有助于临床诊断免疫性血小板减少性紫癜合并幽门螺杆菌的感染。     

Risk analysis of aseptic meningitis after measles-mumps-rubella vaccination in Korean children by using a case-crossover design

Epidemiologic study of a vaccine's adverse events is not easy; so many countries have no reliable data. Vaccines containing the Urabe or Hoshino strain have been withdrawn from use in several countries. However, the data are not strong enough to form the basis of a recommendation not to use specific strains. The authors used a case-crossover design to estimate the relative risk of aseptic meningitis in children after receiving the measles-mumps-rubella vaccine in Korea. Study subjects were hospitalized children aged 8-36 months who had aseptic meningitis in 1998. Cases were confirmed by hospital chart reviews using previously defined criteria. Through a telephone survey, the authors obtained vaccination date and place information from parents' vaccination records. Study results showed that no significant risk was associated with the Jeryl Lynn or Rubini strain of the vaccine (relative risk = 0.6, 95% confidence interval (CI): 0.18, 1.97). For the Urabe or Hoshino strain, the relative risk was 5.5 (95% CI: 2.6, 11.8); the risk increased in the third week after vaccination (relative risk = 15.6, 95% CI: 5.9, 41.2) and was elevated until the sixth week. The case-crossover design was useful in confirming the risk of acute adverse events after receiving vaccines.     

Understanding variation in measles-mumps-rubella immunization coverage--a population-based study

BACKGROUND: Coverage of the Measles-Mumps-Rubella combined vaccine (MMR) has declined in recent years in the UK, following adverse publicity about possible links between the vaccine, autism, and Crohn's disease. The objectives of this study were to assess geographical variation in trends in MMR coverage and to identify the factors affecting MMR uptake at population level. METHODS: We conducted an ecological study of immunization coverage by second birthday, based on routinely collected data from 1993-2004 for England. Trends in MMR uptake were assessed in 95 District Health Authorities in England over the study period. We investigated the relationship between MMR immunization uptake and deprivation, ethnicity, education, population density, rurality, and socioeconomic class. RESULTS: Since 2000, MMR coverage has declined significantly in virtually all areas of England. Population density and deprivation were both strongly correlated with low MMR uptake. The decline in coverage since 1993-94 was significantly related to the proportion of educated population and was greater in densely populated areas. CONCLUSION: Decline in MMR coverage now affects most areas of England. The lowest rates of MMR coverage remain in urban areas, particularly in inner cities, which also tend to show high levels of deprivation. Public health resources should continue to target inner city areas, as well as focus on the concerns of the better educated about vaccine safety.     

儿童特发性血小板减少性紫癜202例临床分析

目的分析儿童特发性血小板减少性紫癜(idiopathic thrombocytopenic purpura,ITP)的临床表现及治疗情况,比较急、慢性ITP的不同点。方法对安徽医科大学第一附属医院2008年1月~2010年12月期间,住院的202例ITP病例临床资料进行回顾性分析。结果 202例ITP患儿,男106例(52.48%),女96例(47.52%),急性ITP 177例(87.62%),慢性、难治性ITP 25例(12.38%),6岁及以下患儿156例(77.23%),6岁以上46例(22.77%);有174例(86.14%)ITP患儿发病时血小板呈重度、极重度减少,但临床多为轻度出血(81.68%);急性组单用激素治疗有效率89.66%,单用丙种球蛋白治疗有效率73.33%,两者联合治疗有效率为88.98%;慢性、难治性ITP激素联合丙种球蛋白治疗有效率54.55%。结论儿童ITP多见于6岁及以下,男女发病机会均等,该病临床发病急而症状轻。对急性ITP应用激素和(或)丙种球蛋白治疗可取得较好的疗效。     

特发性血小板减少性紫癜患者糖皮质激素治疗期感染的危险因素分析

目的探讨接受糖皮质激素治疗的特发性血小板减少性紫癜(ITP)患者感染危险因素,以期为临床该类患者减少感染提供科学有效的依据。方法回顾性分析2007-2012年41例接受糖皮质激素治疗的ITP患者临床资料,采用SPSS17.0软件对所有数据进行统计分析,采用单因素分析和多因素logistic回归分析法找出导致接受糖皮质激素激素治疗的ITP患者感染的危险因素。结果年龄>60岁、女性、有侵入性操作、住院>6周、合并糖尿病及缺铁性贫血患者感染率分别为11.61%、7.36%、12.78%、19.05%、20.63%及14.71%,均高于≤60岁、男性、无侵入性操作、住院≤6周、无糖尿病及无贫血患者的4.60%、3.64%、3.33%、2.86%、4.26%及4.75%;使用抗菌药物患者感染率1.83%,低于未使用抗菌药物患者的7.37%;激素用量过大、不及时减量的患者感染率均较高;以上因素差异均有统计学意义(P<0.05)。结论高龄、女性、合并糖尿病、激素治疗未及时减量的ITP患者发生医院感染的风险较大,临床应给与重视,而使用抗菌药物治疗可以降低ITP感染发生。     

大剂量地塞米松对ITP患者调节性T细胞及叉头状转录因子FoxP3表达的影响

目的:观察特发性血小板减少性紫癜(ITP)患者调节性T细胞(Treg)和叉头状转录因子FoxP3的表达情况及地塞米松治疗前后的变化。方法:用流式细胞术检测ITP患者外周血Treg、FoxP3的表达情况并与正常人群进行比较、并同时记录大剂量地塞米松治疗前后ITP患者Treg、FoxP3的表达情况,比较激素治疗对机体免疫的影响。结果:ITP患者外周血中CD4+T细胞的比例显著低于正常组(P<0.05),CD4+CD25+Treg及CD4+CD25+T在总CD4+T细胞中所占比例也低于正常对照组(P<0.05)。ITP患者未经激素治疗前外周血中FoxP3表达比例明显低于正常对照组(P<0.05),经大剂量地塞米松治疗后Foxp3表达比例升高(P<0.05),与正常人群比较差别仍有统计学意义(P<0.05)。结论:ITP患者的Foxp3表达下降,CD4+CD25+Treg细胞患者数量减少,Treg及Foxp3在ITP的发生发展中起到重要作用,大剂量地塞米松可显著提高CD4+CD25+Treg及FoxP3的表达。     

单病种护理质量控制在小儿特发性血小板减少性紫癜中的应用

目的 探讨单病种护理质量控制在小儿特发性血小板减少性紫癜中的应用效果。方法 将我院2020年1月—2021年6月收治的60例特发性血小板减少性紫癜患儿按照随机数字表法进行编号和分组,其中单号患儿纳入为对照组(30例),接受传统护理模式;双号为观察组(30例),按照小儿特发性血小板减少性紫癜护理质量控制标准分阶段实施评估,制定护理计划,落实护理措施。比较两组患儿:⑴临床治疗相关指标(治疗有效率、平均住院时间及住院费用);⑵护理水平相关指标(护理质量、护理人员业务能力);⑶护理效果相关指标(护理依从性、健康教育知晓率及护理满意度)。结果 ⑴观察组治疗总有效率为80.00%(24/30)高于对照组53.33%(16/30)(χ2=4.800,P=0.028);观察组住院时间及住院费用少于对照组(P<0.001);⑵观察组护理质量及护理人员业务能力高于对照组(P<0.001);⑶护理后,观察组护理依从性、健康教育知晓率及护理满意度高于对照组(P<0.006～0.010)。结论 实施单病种护理质量控制标准管理,有利于提高患儿临床治疗效果及护理效果,提升护理水平,缩短住院时间及费用。     

环孢素A与长春新碱治疗免疫性血小板减少性紫癜的效果

目的:探究对比环孢素A与长春新碱治疗难治性免疫性血小板减少性紫癜的效果.方法:选取医院收治的难治性免疫性血小板减少性紫癜患者43例,随机分为两组,对照组21例、观察组22例,给予对照组患者长春新碱治疗,观察组患者采用环孢素A治疗,比较两组患者治疗总有效率、治疗前后细胞生长因子情况及血小板计数.结果:经环孢素A治疗后,观察组治疗总有效率、治疗后细胞生长因子情况及血小板计数均优于对照组,其差异具有统计学意义(P＜0.05).结论:应用环孢素A治疗难治性免疫性血小板减少性紫癜,患者细胞生长因子及血小板计数恢复较快,治疗总有效率显著提升,临床效果显著.     

儿童慢性特发性血小板减少性紫癜Th1和Th2功能极化分析

目的探讨Th1/Th2极化改变与儿童cITP之间关系。方法流式细胞仪检测21例cITP患儿糖皮质激素治疗前后和28例健康者外周血CD3＋CD8-细胞内IFN-γ和IL-4表达。结果cITP患儿治疗前Th0、Th1细胞和Th1/Th2比值较对照组显著降低（P〈0.01）,治疗后Th0、Th1细胞和Th1/Th2比值较治疗前显著增高（P〈0.01）,与对照组比较,治疗后cITP患儿Th0、Th1细胞增高（P〈0.05）,Th2细胞和Th1/Th2比值无显著差异（P〉0.05）。结论cITP患儿起病时表现为Th1减低,Th2相对优势表达,治疗有效者表现为Th1显著增高,Th2无改变,cITP起病时Th1分泌的IFN-γ分泌减少可促进产生自身抗体,糖皮质激素治疗主要通过增加IFN-γ的分泌达到治疗目的。     

Antibody dynamics after tick-borne encephalitis and measles-mumps-rubella vaccination in children post early thymectomy

Thymectomized patients (TP) showed a delayed humoral immune response to tick-borne-encephalitis-virus (TBEV) vaccination, which served as a neo-antigen. From the previously published cohort, the TBEV-specific IgG concentrations and avidities were analyzed in 17 TP compared to 30 non-thymectomized healthy controls (HC) 220 weeks after the first TBE vaccination to identify patients with waning antibodies. Only in HC, increase of avidity was significant between 8 and 220 weeks (p<0.001), whereas TP showed a lower avidity maturation at week 48 (p<0.05). Cytomegalovirus (CMV) seropositivity at vaccination did not influence the humoral immune response. The ability of TP to maintain measles, mumps and rubella (MMR)-specific antibodies at least 8 years post (MMR) vaccination was evaluated in the serum samples of TP, retrospectively. Although all TP had MMR vaccination at least 6 months after thymectomy, TP showed no significant difference regarding MMR-specific IgG concentrations or avidities compared to HC. Regarding TBE vaccination, the data confirmed the previous observation of a delayed primary immune response in TP to TBE vaccine and also revealed an altered memory priming by paucity of high-avidity antibodies.     

Eltrombopag for the treatment of chronic idiopathic (immune) thrombocytopenic purpura (ITP)

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of eltrombopag for the treatment of adults with chronic idiopathic (immune) thrombocytopenic purpura (ITP), based on a review of the manufacturer's submission (MS) to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. ITP is an autoimmune disorder by which antibodies are formed against platelets with annual incidence rates in the UK/USA ranging from 1.13 to 6.62 cases per 100,000 adults. Eltrombopag increases the production of platelets at a rate that outpaces their destruction by the immune system, and has a UK marketing authorisation both for the treatment of adult ITP in splenectomised patients who are refractory to other treatments and as a second-line treatment for adult non-splenectomised patients for whom surgery is contraindicated. Both splenectomised and non-splenectomised patient groups were considered in the analysis. Two economic models were presented, one for a watch-and-rescue treatment scenario and the second for the long-term treatment of patients with more severe ITP. The submission's evidence was sourced from the relatively high-quality RAISE [RAndomized placebo-controlled Idiopathic thrombocytopenic purpura (ITP) Study with Eltrombopag] randomised controlled trial. The study indicated a statistically significant difference in favour of eltrombopag compared with placebo in the odds of achieving the primary outcome of a platelet count of between 50 and 400 × 109/l during the 6-month treatment period (odds ratio 8.2, 99% confidence interval 3.6 to 18.7). In the eltrombopag group, 50/83 (60%) non-splenectomised patients and 18/49 (37%) splenectomised patients achieved this outcome. Median duration of response for all patients was 10.9 weeks (splenectomised patients 6 weeks and non-splenectomised patients 13.4 weeks). Patients treated with eltrombopag required less rescue medication and had lower odds of bleeding events than placebo-treated subjects in both patient groups. In the watch-and-rescue economic model, the ERG found that substantial reductions in the cost of eltrombopag are needed for the incremental cost-effectiveness ratio (ICER) to fall below ￡ 30,000. Further analyses found that the ICER varied from ￡33,561 to ￡ 103,500 per quality-adjusted life-year (QALY) (splenectomised) and from ￡ 39,657 to ￡ 150,245 per QALY (non-splenectomised). Other than bleeding, no adverse events were modelled. In relation to the long-term treatment model, the ERG found that using non-randomised non-comparative data may result in biased estimates of unknown magnitude and direction. None of the treatment sequences resulted in an ICER approaching the recommended threshold of ￡ 30,000. The base-case results, using a 2-year time horizon and prescribing eltrombopag as second-line treatment post rituximab, were found to be favourable towards eltrombopag. In conclusion, based on the MS and additional ERG work, eltrombopag appears to be a safe treatment for ITP (although long-term follow-up studies are awaited) and has short-term efficacy. However, there is no robust evidence on long-term efficacy or cost-effectiveness of eltrombopag, and there is a lack of robust direct evidence on the effectiveness and cost-effectiveness of eltrombopag compared with other relevant comparators. NICE did not recommend eltrombopag for the treatment of chronic ITP within its marketing authorisation for splenectomised or non-splenectomised patients.