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部分接种疫苗成年人的急性麻疹脑炎。

Acute measles encephalitis in partially vaccinated adults.

机构信息

Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City and Ha Noi, Viet Nam.

出版信息

PLoS One. 2013 Aug 13;8(8):e71671. doi: 10.1371/journal.pone.0071671. eCollection 2013.

Abstract

BACKGROUND

The pathogenesis of acute measles encephalitis (AME) is poorly understood. Treatment with immune-modulators is based on theories that post-infectious autoimmune responses cause demyelination. The clinical course and immunological parameters of AME were examined during an outbreak in Vietnam.

METHODS AND FINDINGS

Fifteen measles IgM-positive patients with confusion or Glasgow Coma Scale (GCS) score below 13, and thirteen with uncomplicated measles were enrolled from 2008-2010. Standardized clinical exams were performed and blood collected for lymphocyte and measles- and auto-antibody analysis. The median age of AME patients was 21 years, similar to controls. Eleven reported receiving measles vaccination when aged one year. Confusion developed a median of 4 days after rash. Six patients had GCS <8 and four required mechanical ventilation. CSF showed pleocytosis (64%) and proteinorrhachia (71%) but measles virus RNA was not detected. MRI revealed bilateral lesions in the cerebellum and brain stem in some patients. Most received dexamethasone +/- IVIG within 4 days of admission but symptoms persisted for ≥3 weeks in five. The concentration of voltage gated calcium channel-complex-reactive antibodies was 900 pM in one patient, and declined to 609 pM ∼ 3 months later. Measles-reactive IgG antibody avidity was high in AME patients born after vaccine coverage exceeded 50% (∼ 25 years earlier). AME patients had low CD4 (218/µl, p = 0.029) and CD8 (200/µl, p = 0.012) T-cell counts compared to controls.

CONCLUSION

Young adults presenting with AME in Vietnam reported a history of one prior measles immunization, and those aged <25 years had high measles-reactive IgG avidity indicative of prior vaccination. This suggests that one-dose measles immunization is not sufficient to prevent AME in young adults and reinforces the importance of maintaining high coverage with a two-dose measles immunization schedule. Treatment with corticosteroids and IVIG is common practice, and should be assessed in randomized clinical trials.

摘要

背景

急性麻疹性脑炎(AME)的发病机制尚不清楚。免疫调节剂的治疗基于感染后自身免疫反应导致脱髓鞘的理论。本研究对越南麻疹流行期间AME 的临床过程和免疫参数进行了研究。

方法和发现

2008 年至 2010 年期间,共纳入了 15 名麻疹 IgM 阳性且意识模糊或格拉斯哥昏迷量表(GCS)评分低于 13 分的患者,以及 13 名无并发症的麻疹患者。进行了标准化的临床检查,并采集血液进行淋巴细胞和麻疹及自身抗体分析。AME 患者的中位年龄为 21 岁,与对照组相似。11 名患者报告在 1 岁时接种过麻疹疫苗。皮疹后中位 4 天出现意识模糊。6 名患者 GCS<8,4 名患者需要机械通气。CSF 显示细胞增多症(64%)和蛋白血症(71%),但未检测到麻疹病毒 RNA。MRI 显示一些患者小脑和脑干双侧病变。大多数患者在入院后 4 天内接受地塞米松 +/-IVIG,但 5 名患者的症状持续了≥3 周。一名患者电压门控钙通道复合物反应性抗体浓度为 900 pM,约 3 个月后降至 609 pM。麻疹反应性 IgG 抗体亲和力在疫苗覆盖率超过 50%(约 25 年前)后出生的 AME 患者中较高(约 25 年前)。AME 患者的 CD4(218/µl,p=0.029)和 CD8(200/µl,p=0.012)T 细胞计数低于对照组。

结论

越南年轻成人 AME 患者报告有一次麻疹免疫接种史,年龄<25 岁的患者麻疹反应性 IgG 亲和力较高,提示一次麻疹免疫接种不足以预防年轻成人 AME,强化了两剂麻疹免疫接种计划保持高覆盖率的重要性。皮质类固醇和 IVIG 的治疗是常见的做法,应在随机临床试验中进行评估。

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