RESUMO
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 Restauração, 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-Barré syndrome (25 [61%] patients). Patients with Guillain-Barré 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. FUNDING: Fundação do Amparo a Ciência e Tecnologia de Pernambuco (FACEPE), EU's Horizon 2020 research and innovation programme, National Institute for Health Research. TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.
Assuntos
Febre de Chikungunya/diagnóstico , Febre de Chikungunya/epidemiologia , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/epidemiologia , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia , Adulto , Idoso , Brasil/epidemiologia , Febre de Chikungunya/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/sangue , Estudos Prospectivos , Infecção por Zika virus/sangueRESUMO
BACKGROUND: During 2015-16 Brazil experienced the largest epidemic of Zika virus ever reported. This arthropod-borne virus (arbovirus) has been linked to Guillain-Barré syndrome (GBS) in adults but other neurological associations are uncertain. Chikungunya virus has caused outbreaks in Brazil since 2014 but associated neurological disease has rarely been reported here. We investigated adults with acute neurological disorders for Zika, chikungunya and dengue, another arbovirus circulating in Brazil. METHODS: We studied adults who had developed a new neurological condition following suspected Zika virus infection between 1st November 2015 and 1st June 2016. Cerebrospinal fluid (CSF), serum, and urine were tested for evidence of Zika, chikungunya, and dengue viruses. RESULTS: Of 35 patients studied, 22 had evidence of recent arboviral infection. Twelve had positive PCR or IgM for Zika, five of whom also had evidence for chikungunya, three for dengue, and one for all three viruses. Five of them presented with GBS; seven had presentations other than GBS, including meningoencephalitis, myelitis, radiculitis or combinations of these syndromes. Additionally, ten patients positive for chikungunya virus, two of whom also had evidence for dengue virus, presented with a similar range of neurological conditions. CONCLUSIONS: Zika virus is associated with a wide range of neurological manifestations, including central nervous system disease. Chikungunya virus appears to have an equally important association with neurological disease in Brazil, and many patients had dual infection. To understand fully the burden of Zika we must look beyond GBS, and also investigate for other co-circulating arboviruses, particularly chikungunya.