Neurological disease in adults with Zika and chikungunya virus infection in Northeast Brazil: a prospective observational study

Maria Lúcia Brito Ferreira, Maria de Fatima Pessoa Militão de Albuquerque, Carlos Alexandre Antunes de Brito, Rafael Freitas de Oliveira França, Álvaro José Porto Moreira, Maria Íris de Morais Machado, Roberta da Paz Melo, Raquel Medialdea-Carrera, Solange Dornelas Mesquita, Marcela Lopes Santos, Ravi Mehta, Rafael Ramos e Silva, Sonja E. Leonhard, Mark Ellul, Anna Rosala-Hallas, Girvan Burnside, Lance Turtle, Michael J. Griffiths, Bart C. Jacobs, Maneesh BhojakHugh J. Willison, Lindomar José Pena, Carlos A. Pardo, Ricardo A.A. Ximenes, Celina Maria Turchi Martelli, David Brown, Marli Tenório Cordeiro, Suzannah Lant, Tom Solomon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)826-839
Number of pages14
JournalThe Lancet Neurology
Volume19
Issue number10
DOIs
Publication statusPublished - Oct 2020

Bibliographical note

Funding Information:
This work was supported by Fundação do Amparo a Ciência e Tecnologia de Pernambuco (FACEPE; APQ-1623–4.01/15) and the EU Zika Preparedness Latin American Network consortium (ZikaPLAN). ZikaPLAN has received funding from the EU's Horizon 2020 research and innovation programme under grant agreement number 734584. DWGB is also partly supported by the EU's Horizon 2020 research and innovation programme grant agreement number 734857 as part of the Zikaction consortium. RM-C, RM, MJG, ME, LT, SL, and TS are also supported by the National Institute for Health Research (NIHR) Health Protection Research Unit in Emerging and Zoonotic Infections (NIHR200907) at the University of Liverpool (Liverpool, UK), in partnership with Public Health England, in collaboration with Liverpool School of Tropical Medicine and the University of Oxford, and two NIHR programme grants (RP-PG-0108–10,048 and 17/63/110). CAP is supported by a National Institutes of Health grant R01 NS110122. HJW is supported by a Wellcome Trust award (WT 202789/Z/16/Z). LT is a Wellcome clinical career development fellow, supported by grant number 205228/Z/16/Z. This work was conducted independently of influence from the NIHR and the views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, the Department of Health, or Public Health England.

Funding Information:
This work was supported by Funda??o do Amparo a Ci?ncia e Tecnologia de Pernambuco (FACEPE; APQ-1623?4.01/15) and the EU Zika Preparedness Latin American Network consortium (ZikaPLAN). ZikaPLAN has received funding from the EU's Horizon 2020 research and innovation programme under grant agreement number 734584. DWGB is also partly supported by the EU's Horizon 2020 research and innovation programme grant agreement number 734857 as part of the Zikaction consortium. RM-C, RM, MJG, ME, LT, SL, and TS are also supported by the National Institute for Health Research (NIHR) Health Protection Research Unit in Emerging and Zoonotic Infections (NIHR200907) at the University of Liverpool (Liverpool, UK), in partnership with Public Health England, in collaboration with Liverpool School of Tropical Medicine and the University of Oxford, and two NIHR programme grants (RP-PG-0108?10,048 and 17/63/110). CAP is supported by a National Institutes of Health grant R01 NS110122. HJW is supported by a Wellcome Trust award (WT 202789/Z/16/Z). LT is a Wellcome clinical career development fellow, supported by grant number 205228/Z/16/Z. This work was conducted independently of influence from the NIHR and the views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, the Department of Health, or Public Health England.

Publisher Copyright:
© 2020 Elsevier Ltd

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

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