Guillain-Barré syndrome during the Zika virus outbreak in Northeast Brazil: An observational cohort study

Sonja E. Leonhard; Susan Halstead; Suzannah B. Lant; Maria de Fatima Pessoa Militão de Albuquerque; Carlos Alexandre Antunes de Brito; Lívia Brito Bezerra de Albuquerque; Mark A. Ellul; Rafael Freitas de Oliveira França; Dawn Gourlay; Michael J. Griffiths; Adélia Maria de Miranda Henriques-Souza; Maria de Morais Machado; Raquel Medialdea-Carrera; Ravi Mehta; Roberta da Paz Melo; Solange D. Mesquita; Álvaro J.P. Moreira; Lindomar J. Pena; Marcela Lopes Santos; Lance Turtle; Tom Solomon; Hugh J. Willison; Bart C. Jacobs; Maria L. Brito Ferreira

doi:10.1016/j.jns.2020.117272

Guillain-Barré syndrome during the Zika virus outbreak in Northeast Brazil: An observational cohort study

Sonja E. Leonhard^*, Susan Halstead, Suzannah B. Lant, Maria de Fatima Pessoa Militão de Albuquerque, Carlos Alexandre Antunes de Brito, Lívia Brito Bezerra de Albuquerque, Mark A. Ellul, Rafael Freitas de Oliveira França, Dawn Gourlay, Michael J. Griffiths, Adélia Maria de Miranda Henriques-Souza, Maria de Morais Machado, Raquel Medialdea-Carrera, Ravi Mehta, Roberta da Paz Melo, Solange D. Mesquita, Álvaro J.P. Moreira, Lindomar J. Pena, Marcela Lopes Santos, Lance TurtleTom Solomon, Hugh J. Willison, Bart C. Jacobs, Maria L. Brito Ferreira

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Objective: To determine the clinical phenotype of Guillain-Barré syndrome (GBS) after Zika virus (ZIKV) infection, the anti-glycolipid antibody signature, and the role of other circulating arthropod-borne viruses, we describe a cohort of GBS patients identified during ZIKV and chikungunya virus (CHIKV) outbreaks in Northeast Brazil. Methods: We prospectively recruited GBS patients from a regional neurology center in Northeast Brazil between December 2014 and February 2017. Serum and CSF were tested for ZIKV, CHIKV, and dengue virus (DENV), by RT-PCR and antibodies, and serum was tested for GBS-associated antibodies to glycolipids. Results: Seventy-one patients were identified. Forty-eight (68%) had laboratory evidence of a recent arbovirus infection; 25 (52%) ZIKV, 8 (17%) CHIKV, 1 (2%) DENV, and 14 (29%) ZIKV and CHIKV. Most patients with a recent arbovirus infection had motor and sensory symptoms (72%), a demyelinating electrophysiological subtype (67%) and a facial palsy (58%). Patients with a recent infection with ZIKV and CHIKV had a longer hospital admission and more frequent mechanical ventilation compared to the other patients. No specific anti-glycolipid antibody signature was identified in association with arbovirus infection, although significant antibody titres to GM1, GalC, LM1, and GalNAc-GD1a were found infrequently. Conclusion: A large proportion of cases had laboratory evidence of a recent infection with ZIKV or CHIKV, and recent infection with both viruses was found in almost one third of patients. Most patients with a recent arbovirus infection had a sensorimotor, demyelinating GBS. We did not find a specific anti-glycolipid antibody signature in association with arbovirus-related GBS.

Original language	English
Article number	117272
Journal	Journal of the Neurological Sciences
Volume	420
DOIs	https://doi.org/10.1016/j.jns.2020.117272
Publication status	Published - 15 Jan 2021

Bibliographical note

Study funding:
This work was supported by Fundação do Amparo a Ciência e Tecnologia (FACEPE) (APQ-1623-4.01/15) and the Zika Preparedness Latin American Network.

Consortium (ZikaPLAN). ZikaPLAN has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement no. 734584. RMC, RM, ME, LT, SL and TS are supported by the National Institute for Health Research (NIHR) Health Protection Research Unit in Emerging and Zoonotic Infections at the University of Liverpool, in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (Grant No. IS-HPU-1112-10,117 and NIHR200907), and two NIHR Program Grants (RP-PG-0108-10,048 and 17/63/110). HJW, SH and DG are supported by the Wellcome Trust (grant numbers 092805 and 202,789).

The funding resources did not have any role in the writing of the manuscript or the decision to submit for publication.

Publisher Copyright: © 2020 The Author(s)

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Leonhard, S. E., Halstead, S., Lant, S. B., Militão de Albuquerque, M. D. F. P., de Brito, C. A. A., de Albuquerque, L. B. B., Ellul, M. A., de Oliveira França, R. F., Gourlay, D., Griffiths, M. J., de Miranda Henriques-Souza, A. M., de Morais Machado, M., Medialdea-Carrera, R., Mehta, R., da Paz Melo, R., Mesquita, S. D., Moreira, Á. J. P., Pena, L. J., Santos, M. L., ... Brito Ferreira, M. L. (2021). Guillain-Barré syndrome during the Zika virus outbreak in Northeast Brazil: An observational cohort study. Journal of the Neurological Sciences, 420, Article 117272. https://doi.org/10.1016/j.jns.2020.117272

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title = "Guillain-Barr{\'e} syndrome during the Zika virus outbreak in Northeast Brazil: An observational cohort study",

abstract = "Objective: To determine the clinical phenotype of Guillain-Barr{\'e} syndrome (GBS) after Zika virus (ZIKV) infection, the anti-glycolipid antibody signature, and the role of other circulating arthropod-borne viruses, we describe a cohort of GBS patients identified during ZIKV and chikungunya virus (CHIKV) outbreaks in Northeast Brazil. Methods: We prospectively recruited GBS patients from a regional neurology center in Northeast Brazil between December 2014 and February 2017. Serum and CSF were tested for ZIKV, CHIKV, and dengue virus (DENV), by RT-PCR and antibodies, and serum was tested for GBS-associated antibodies to glycolipids. Results: Seventy-one patients were identified. Forty-eight (68%) had laboratory evidence of a recent arbovirus infection; 25 (52%) ZIKV, 8 (17%) CHIKV, 1 (2%) DENV, and 14 (29%) ZIKV and CHIKV. Most patients with a recent arbovirus infection had motor and sensory symptoms (72%), a demyelinating electrophysiological subtype (67%) and a facial palsy (58%). Patients with a recent infection with ZIKV and CHIKV had a longer hospital admission and more frequent mechanical ventilation compared to the other patients. No specific anti-glycolipid antibody signature was identified in association with arbovirus infection, although significant antibody titres to GM1, GalC, LM1, and GalNAc-GD1a were found infrequently. Conclusion: A large proportion of cases had laboratory evidence of a recent infection with ZIKV or CHIKV, and recent infection with both viruses was found in almost one third of patients. Most patients with a recent arbovirus infection had a sensorimotor, demyelinating GBS. We did not find a specific anti-glycolipid antibody signature in association with arbovirus-related GBS.",

author = "Leonhard, {Sonja E.} and Susan Halstead and Lant, {Suzannah B.} and {Milit{\~a}o de Albuquerque}, {Maria de Fatima Pessoa} and {de Brito}, {Carlos Alexandre Antunes} and {de Albuquerque}, {L{\'i}via Brito Bezerra} and Ellul, {Mark A.} and {de Oliveira Fran{\c c}a}, {Rafael Freitas} and Dawn Gourlay and Griffiths, {Michael J.} and {de Miranda Henriques-Souza}, {Ad{\'e}lia Maria} and {de Morais Machado}, Maria and Raquel Medialdea-Carrera and Ravi Mehta and {da Paz Melo}, Roberta and Mesquita, {Solange D.} and Moreira, {{\'A}lvaro J.P.} and Pena, {Lindomar J.} and Santos, {Marcela Lopes} and Lance Turtle and Tom Solomon and Willison, {Hugh J.} and Jacobs, {Bart C.} and {Brito Ferreira}, {Maria L.}",

note = "Study funding: This work was supported by Funda{\c c}{\~a}o do Amparo a Ci{\^e}ncia e Tecnologia (FACEPE) (APQ-1623-4.01/15) and the Zika Preparedness Latin American Network. Consortium (ZikaPLAN). ZikaPLAN has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement no. 734584. RMC, RM, ME, LT, SL and TS are supported by the National Institute for Health Research (NIHR) Health Protection Research Unit in Emerging and Zoonotic Infections at the University of Liverpool, in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (Grant No. IS-HPU-1112-10,117 and NIHR200907), and two NIHR Program Grants (RP-PG-0108-10,048 and 17/63/110). HJW, SH and DG are supported by the Wellcome Trust (grant numbers 092805 and 202,789). The funding resources did not have any role in the writing of the manuscript or the decision to submit for publication. Publisher Copyright: {\textcopyright} 2020 The Author(s)",

year = "2021",

month = jan,

day = "15",

doi = "10.1016/j.jns.2020.117272",

language = "English",

volume = "420",

journal = "Journal of the Neurological Sciences",

issn = "0022-510X",

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Leonhard, SE, Halstead, S, Lant, SB, Militão de Albuquerque, MDFP, de Brito, CAA, de Albuquerque, LBB, Ellul, MA, de Oliveira França, RF, Gourlay, D, Griffiths, MJ, de Miranda Henriques-Souza, AM, de Morais Machado, M, Medialdea-Carrera, R, Mehta, R, da Paz Melo, R, Mesquita, SD, Moreira, ÁJP, Pena, LJ, Santos, ML, Turtle, L, Solomon, T, Willison, HJ, Jacobs, BC & Brito Ferreira, ML 2021, 'Guillain-Barré syndrome during the Zika virus outbreak in Northeast Brazil: An observational cohort study', Journal of the Neurological Sciences, vol. 420, 117272. https://doi.org/10.1016/j.jns.2020.117272

TY - JOUR

T1 - Guillain-Barré syndrome during the Zika virus outbreak in Northeast Brazil

T2 - An observational cohort study

AU - Leonhard, Sonja E.

AU - Halstead, Susan

AU - Lant, Suzannah B.

AU - Militão de Albuquerque, Maria de Fatima Pessoa

AU - de Brito, Carlos Alexandre Antunes

AU - de Albuquerque, Lívia Brito Bezerra

AU - Ellul, Mark A.

AU - de Oliveira França, Rafael Freitas

AU - Gourlay, Dawn

AU - Griffiths, Michael J.

AU - de Miranda Henriques-Souza, Adélia Maria

AU - de Morais Machado, Maria

AU - Medialdea-Carrera, Raquel

AU - Mehta, Ravi

AU - da Paz Melo, Roberta

AU - Mesquita, Solange D.

AU - Moreira, Álvaro J.P.

AU - Pena, Lindomar J.

AU - Santos, Marcela Lopes

AU - Turtle, Lance

AU - Solomon, Tom

AU - Willison, Hugh J.

AU - Jacobs, Bart C.

AU - Brito Ferreira, Maria L.

N1 - Study funding: This work was supported by Fundação do Amparo a Ciência e Tecnologia (FACEPE) (APQ-1623-4.01/15) and the Zika Preparedness Latin American Network. Consortium (ZikaPLAN). ZikaPLAN has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement no. 734584. RMC, RM, ME, LT, SL and TS are supported by the National Institute for Health Research (NIHR) Health Protection Research Unit in Emerging and Zoonotic Infections at the University of Liverpool, in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (Grant No. IS-HPU-1112-10,117 and NIHR200907), and two NIHR Program Grants (RP-PG-0108-10,048 and 17/63/110). HJW, SH and DG are supported by the Wellcome Trust (grant numbers 092805 and 202,789). The funding resources did not have any role in the writing of the manuscript or the decision to submit for publication. Publisher Copyright: © 2020 The Author(s)

PY - 2021/1/15

Y1 - 2021/1/15

N2 - Objective: To determine the clinical phenotype of Guillain-Barré syndrome (GBS) after Zika virus (ZIKV) infection, the anti-glycolipid antibody signature, and the role of other circulating arthropod-borne viruses, we describe a cohort of GBS patients identified during ZIKV and chikungunya virus (CHIKV) outbreaks in Northeast Brazil. Methods: We prospectively recruited GBS patients from a regional neurology center in Northeast Brazil between December 2014 and February 2017. Serum and CSF were tested for ZIKV, CHIKV, and dengue virus (DENV), by RT-PCR and antibodies, and serum was tested for GBS-associated antibodies to glycolipids. Results: Seventy-one patients were identified. Forty-eight (68%) had laboratory evidence of a recent arbovirus infection; 25 (52%) ZIKV, 8 (17%) CHIKV, 1 (2%) DENV, and 14 (29%) ZIKV and CHIKV. Most patients with a recent arbovirus infection had motor and sensory symptoms (72%), a demyelinating electrophysiological subtype (67%) and a facial palsy (58%). Patients with a recent infection with ZIKV and CHIKV had a longer hospital admission and more frequent mechanical ventilation compared to the other patients. No specific anti-glycolipid antibody signature was identified in association with arbovirus infection, although significant antibody titres to GM1, GalC, LM1, and GalNAc-GD1a were found infrequently. Conclusion: A large proportion of cases had laboratory evidence of a recent infection with ZIKV or CHIKV, and recent infection with both viruses was found in almost one third of patients. Most patients with a recent arbovirus infection had a sensorimotor, demyelinating GBS. We did not find a specific anti-glycolipid antibody signature in association with arbovirus-related GBS.

AB - Objective: To determine the clinical phenotype of Guillain-Barré syndrome (GBS) after Zika virus (ZIKV) infection, the anti-glycolipid antibody signature, and the role of other circulating arthropod-borne viruses, we describe a cohort of GBS patients identified during ZIKV and chikungunya virus (CHIKV) outbreaks in Northeast Brazil. Methods: We prospectively recruited GBS patients from a regional neurology center in Northeast Brazil between December 2014 and February 2017. Serum and CSF were tested for ZIKV, CHIKV, and dengue virus (DENV), by RT-PCR and antibodies, and serum was tested for GBS-associated antibodies to glycolipids. Results: Seventy-one patients were identified. Forty-eight (68%) had laboratory evidence of a recent arbovirus infection; 25 (52%) ZIKV, 8 (17%) CHIKV, 1 (2%) DENV, and 14 (29%) ZIKV and CHIKV. Most patients with a recent arbovirus infection had motor and sensory symptoms (72%), a demyelinating electrophysiological subtype (67%) and a facial palsy (58%). Patients with a recent infection with ZIKV and CHIKV had a longer hospital admission and more frequent mechanical ventilation compared to the other patients. No specific anti-glycolipid antibody signature was identified in association with arbovirus infection, although significant antibody titres to GM1, GalC, LM1, and GalNAc-GD1a were found infrequently. Conclusion: A large proportion of cases had laboratory evidence of a recent infection with ZIKV or CHIKV, and recent infection with both viruses was found in almost one third of patients. Most patients with a recent arbovirus infection had a sensorimotor, demyelinating GBS. We did not find a specific anti-glycolipid antibody signature in association with arbovirus-related GBS.

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U2 - 10.1016/j.jns.2020.117272

DO - 10.1016/j.jns.2020.117272

M3 - Article

C2 - 33360425

SN - 0022-510X

VL - 420

JO - Journal of the Neurological Sciences

JF - Journal of the Neurological Sciences

M1 - 117272

ER -

Guillain-Barré syndrome during the Zika virus outbreak in Northeast Brazil: An observational cohort study

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