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.     

补肾活血方对原发性免疫性血小板减少症小鼠肠道免疫及淋巴细胞周期的影响

目的:通过研究补肾活血方对原发性免疫性血小板减少症(ITP)模型小鼠免疫系统的影响,探讨补肾活血方治疗ITP的效果及作用机制。方法:建立ITP小鼠模型,ELISA法检测小鼠肠黏液中免疫球蛋白的含量及小鼠肠系膜淋巴结淋巴细胞P53蛋白表达的变化;流式细胞仪检测小鼠肠系膜淋巴结淋巴细胞周期及淋巴细胞凋亡率的变化。结果:补肾活血方能够显著下调小鼠肠黏液中免疫球蛋白含量(P<0.05);下调P53蛋白表达,与模型组比较差异有统计学意义(P<0.01);显著升高G0/G1期淋巴细胞比例(P<0.05),降低S期淋巴细胞比例(P<0.05),降低淋巴细胞凋亡率(P<0.05),对淋巴细胞周期异常分布及异常凋亡有一定的改善作用。结论:补肾活血方对ITP小鼠有明显的治疗作用,其作用机制主要表现为下调ITP小鼠IgG、SIgA含量及淋巴细胞P53蛋白表达、改善ITP小鼠淋巴细胞周期异常分布、降低淋巴细胞凋亡率等,其具体机制有待进一步的研究探索。     

ITP患儿血小板内cAMP的研究

本文用放免法测定了38例正常儿及47例 ITP 患儿血小板内 cAMP 值。发现无论急、慢性患儿血小板内 cAMP 值均显著增高,其增高与血小板功能呈负相关,与血小板计数无相关性。急性患儿 PAIgG 增高,血小板内 cAMP 亦增高,二者之间呈正相关,而慢性患儿则无此相关性。并对 cAMP 的增高与 ITP 的发病机制进行了阐述。     

Rituximab in the management of chronic immune thrombocytopenic purpura: an effective and safe therapeutic alternative in refractory patients

Rituximab induces B-cell depletion; therefore, it has been used in the treatment of immune thrombocytopenic purpura (ITP). The aim of this retrospective study was to evaluate the effectiveness of rituximab in the treatment of 89 patients with chronic ITP refractory to several treatments. All the patients had platelet counts <30×10⁹/l. They had received a median of five (2–13) previous treatments, and 47 had undergone splenectomy. Rituximab was administered i.v. at 375 mg/m² in four weekly doses in 77 patients, and 12 patients received 1–6 doses. Forty-nine patients (55.1%) reached platelet counts >50×10⁹/l; 41 (46%) achieved a complete response (CR; platelets >100×10⁹/l), and eight (9%) obtained a partial response (platelets 50–100×10⁹/l). Overall, 31 patients (35%) maintained response, including 15 patients in whom splenectomy failed, with a median follow-up of 9 months (2–42), 12 for more than 1 year. The unique predictor of a maintained response was to reach a CR. Heavily treated patients (more than three different previous treatments, including any corticosteroids) and those with longer ITP duration (>10 years from diagnosis) had a worse response. Non-splenectomized patients had a better early response rate than those splenectomized. Rituximab was well tolerated, with two fever episodes following infusion and two reports of skin rash. Rituximab induced clinical responses in multi-treated refractory ITP patients with little toxicity and should be considered as an early therapeutic option in this setting, even as an alternative to splenectomy in selected patients.An erratum to this article can be found at     

CD47 is expressed at normal levels in patients with autoimmune haemolytic anaemia and/or immune thrombocytopenia

CD47 deficiency results in lethal autoimmune haemolytic anaemia (AIHA) and mild spontaneous thrombocytopenia in non-obese diabetic mice. It is unknown whether CD47 has an impact on AIHA of the warm type or autoimmune thrombocytopenia (ITP) in humans. Healthy blood donors (n= 11), patients with AIHA (n= 13), patients with ITP (n= 18) and one patient with Rh(null) phenotype were investigated. CD47 expression on red blood cells (RBC), platelets, granulocytes and lymphocytes and in plasma was determined by quantitative flow cytometry. All types of blood cells studied were found to carry CD47. Although CD47 expression on Rh(null) RBCs was decreased, there was no significant difference between CD47 expression on RBCs of healthy blood donors and on those of patients with AIHA or ITP. Similarly, CD47 was detectable in the plasma of the studied subjects. No evidence for a pathogenetic role of CD47 in autoimmune haemolysis or thrombocytopenia in humans could be demonstrated.     

多抗甲素注射液加小剂量脾区放疗ITP43例疗效观察

目的 探讨难治性特发性血小板减少性紫癜(ITP)的治疗方法。方法 多抗甲素注射液加小剂量脾区放疗，总剂量800—1200cGy。结果 43例患接受2个疗程的多抗甲素静滴及2个疗程的脾区照射，显效26例，良效9例，进步6例，无效2例，总有效率95．3％。结论 多抗甲素注射液作为一种免疫制剂，能直接提升血小板，使破坏了的血小板得到新生，而脾区照射可减少血小板的破坏和PAIgG的产生，因此认为2种方法合用对顽固性ITP的治疗提供了新的治疗途径。     

小剂量美罗华联合重组人血小板生成素治疗难治性特发性血小板减少性紫癜的护理

目的探讨小剂量美罗华联合重组人血小板生成素(rh TPO)治疗难治性特发性血小板减少性紫癜(ITP)的疗效及其护理。方法对诊断为难治性ITP的4例患者采用小剂量美罗华联合rh TPO治疗,治疗过程中实施有效的心理护理,严格规范药液的保管、配置及输注,积极预防和处理药物不良反应,并对副作用进行严密观察和护理。结果 4例患者中,1例获完全反应(CR),3例获部分反应(PR),发热1例、肝功能异常1例,所有患者均顺利完成治疗。结论小剂量美罗华联合rh TPO为难治性ITP的治疗提供了新途径,是一种安全有效的治疗方法,精心的护理能有效预防药物的毒副作用,保证治疗效果。     

Efficacy and safety of thrombopoietin receptor agonists in children with chronic immune thrombocytopenic purpura: meta-analysis

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder presenting with low platelet count <100 × 10⁹/L. The condition affects both adults and children. Thrombopoietin receptor agonists (TPO-RAs) are second-line of therapy that includes Romiplostim and Eltrombopag, which stimulate the production of normally functioning platelets. Although the biological effect of these drugs is well established, there has not been a meta-analysis in children. To estimate the efficacy and safety of Romiplostim and Eltrombopag, we performed a systematic review and meta-analysis in children with chronic ITP. Systematic literature search was conducted in the following database: PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL). Review Manager 5.3 for Windows was used to analyze the data. Five randomized controlled trials with total of 261 pediatric patients from 1–17 years of age were included. The efficacy and safety analysis showed TPO-RA groups were superior over placebo, and there was no difference in adverse event occurrence between TPO-RA (Romiplostim and Eltrombopag) and placebo groups. The efficacy and safety of Eltrombopag did not differ significantly from those of Romiplostim. Both drugs were effective in treatment of children with chronic ITP. Our findings extend the currently available data on ITP treatment and is helpful for pediatric health providers and for the design of future clinical trials.