Neurological disease in adults with Zika and chikungunya virus infection in Northeast Brazil: a prospective observational study
Neurological disease in adults with Zika and chikungunya virus infection in Northeast Brazil: a prospective observational study
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DOI：
10.1016/s1474-4422(20)30232-5
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发表时间：
2020-10-01
期刊：
影响因子：
48
通讯作者：
Solomon, Tom
中科院分区：
文献类型：
--
作者：
Brito Ferreira, Maria Lucia;Pessoa Militao de Albuquerque, Maria de Fatima;Solomon, Tom
自2015年以来，背景是节肢动物传播病毒（Arboviruses）Zika和Chikungunya在美洲遍布疫情，伴随着免疫介导的和感染性神经系统疾病的增加。与这些病毒相关的神经表现形式的光谱以及双重感染的重要性尚不完全清楚。我们的目的是研究神经系统介绍是否根据感染的Arbovirus以及双重感染的患者是否具有不同的疾病谱或严重程度。方法性报告了一项前瞻性观察性研究，在Zika和Chikungunya病毒的流行期间进行的一项前瞻性观察性研究，在雷神，佩南布科，七个龙鸟，七个领域。我们招募了18岁或以上的成年人，提到了二级和三级医院DA Restauranacao医院，患有急性神经系统疾病和可疑的灰烬病毒感染史。我们在血清或CSF中寻找寨卡病毒，基孔肯雅或登革热感染的证据。我们根据患者的arbovirus实验室诊断对患者进行了分组，然后比较了人口统计和临床特征。在2014年12月4日至2016年12月4日之间，发现了医院神经病学服务的1410例患者； 201（14％）的症状与Arbovirus感染一致，并且有足够的样本进行诊断测试，并被包括在研究中。中位年龄为48岁（IQR 34-60），女性为106（53％）。 201名患者中有148例（74％）有实验室弧病毒感染的证据。其中98（49％）患有单个病毒感染（41 [20％]患有Zika，55 [27％]患有Chikungunya，而两个[1％]患有登革热感染），而50（25％）有双重感染的证据，大多是Zika和Chikungunya病毒（46％[23％）患者。 arbovirus感染阳性的患者呈现广泛的中枢神经系统和周围神经系统（PNS）疾病。 Chikungunya感染更常见于CNS疾病（55例Chikungunya感染患者中的26例[47％]，而41例患有Zika感染的41例[15％]； P = 0.0008），尤其是脊髓炎（12 [22％]患者）。 Zika感染更常见于PNS疾病（41例Zika感染患者中有26例[63％]，而Chikungunya感染的55例中有9例[16％]； P = 0.0001），尤其是Guillain-Barre综合征（25 [61％]患者）。患有Zika和Chikungunya双重感染的Guillain-Barre综合征患者患有更具侵略性疾病，需要重症监护剂和更长的住院治疗，比单身感染的患者（中位数为24天[IQR 20-30] [IQR 20-30] vs 17天[10-20] [10-20]； P = 0.0028）。在46例寨卡病毒和奇京根尼亚双感染的46例患者中，有8名（17％）具有中风或短暂性缺血性发作，而96例寨卡病毒或chikungunya单一感染的患者中有5例（6％）（P = 0.047）（p = 0.047）。由Zikika或Chikunfundya造成了广泛的和重叠的神经功能和重叠谱。双重感染患者可能会增加急性脑血管疾病的风险。
Background Since 2015, the arthropod-borne viruses (arboviruses) Zika and chikungunya have spread across the Americas causing outbreaks, accompanied by increases in immune-mediated and infectious neurological disease. The spectrum of neurological manifestations linked to these viruses, and the importance of dual infection, are not known fully. We aimed to investigate whether neurological presentations differed according to the infecting arbovirus, and whether patients with dual infection had a different disease spectrum or severity.Methods We report a prospective observational study done during epidemics of Zika and chikungunya viruses in Recife, Pernambuco, a dengue-endemic area of Brazil. We recruited adults aged 18 years or older referred to Hospital da Restauracao, a secondary-level and tertiary-level hospital, with suspected acute neurological disease and a history of suspected arboviral infection. We looked for evidence of Zika, chikungunya, or dengue infection by viral RNA or specific IgM antibodies in serum or CSF. We grouped patients according to their arbovirus laboratory diagnosis and then compared demographic and clinical characteristics.Findings Between Dec 4, 2014, and Dec 4, 2016, 1410 patients were admitted to the hospital neurology service; 201 (14%) had symptoms consistent with arbovirus infection and sufficient samples for diagnostic testing and were included in the study. The median age was 48 years (IQR 34-60), and 106 (53%) were women. 148 (74%) of 201 patients had laboratory evidence of arboviral infection. 98 (49%) of them had a single viral infection (41 [20%] had Zika, 55 [27%] had chikungunya, and two [1%] had dengue infection), whereas 50 (25%) had evidence of dual infection, mostly with Zika and chikungunya viruses (46 [23%] patients). Patients positive for arbovirus infection presented with a broad range of CNS and peripheral nervous system (PNS) disease. Chikungunya infection was more often associated with CNS disease (26 [47%] of 55 patients with chikungunya infection vs six [15%] of 41 with Zika infection; p=0.0008), especially myelitis (12 [22%] patients). Zika infection was more often associated with PNS disease (26 [63%] of 41 patients with Zika infection vs nine [16%] of 55 with chikungunya infection; p=0.0001), particularly Guillain-Barre syndrome (25 [61%] patients). Patients with Guillain-Barre syndrome who had Zika and chikungunya dual infection had more aggressive disease, requiring intensive care support and longer hospital stays, than those with mono-infection (median 24 days [IQR 20-30] vs 17 days [10-20]; p=0.0028). Eight (17%) of 46 patients with Zika and chikungunya dual infection had a stroke or transient ischaemic attack, compared with five (6%) of 96 patients with Zika or chikungunya mono-infection (p=0.047).Interpretation There is a wide and overlapping spectrum of neurological manifestations caused by Zika or chikungunya mono-infection and by dual infections. The possible increased risk of acute cerebrovascular disease in patients with dual infection merits further investigation.