Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City and Ha Noi, Viet Nam.
PLoS One. 2013 Aug 13;8(8):e71671. doi: 10.1371/journal.pone.0071671. eCollection 2013.
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.
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.
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.
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。
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。
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。