The spectrum of neurological disease associated with Zika and chikungunya viruses in adults in Rio de Janeiro, Brazil: A case series

Ravi Mehta; Cristiane Nascimento Soares; Raquel Medialdea-Carrera; Mark Ellul; Marcus Tulius Texeira da Silva; Anna Rosala-Hallas; Marcia Rodrigues Jardim; Girvan Burnside; Luciana Pamplona; Maneesh Bhojak; Radhika Manohar; Gabriel Amorelli Medeiros da Silva; Marcus Vinicius Adriano; Patricia Brasil; Rita Maria Ribeiro Nogueira; Carolina Cardoso Dos Santos; Lance Turtle; Patricia Carvalho de Sequeira; David Brown; Michael J. Griffiths; Ana Maria Bispo de Filippis; Tom Solomon

doi:10.1371/journal.pntd.0006212

The spectrum of neurological disease associated with Zika and chikungunya viruses in adults in Rio de Janeiro, Brazil: A case series

Ravi Mehta^*, Cristiane Nascimento Soares, Raquel Medialdea-Carrera, Mark Ellul, Marcus Tulius Texeira da Silva, Anna Rosala-Hallas, Marcia Rodrigues Jardim, Girvan Burnside, Luciana Pamplona, Maneesh Bhojak, Radhika Manohar, Gabriel Amorelli Medeiros da Silva, Marcus Vinicius Adriano, Patricia Brasil, Rita Maria Ribeiro Nogueira, Carolina Cardoso Dos Santos, Lance Turtle, Patricia Carvalho de Sequeira, David Brown, Michael J. GriffithsAna Maria Bispo de Filippis, Tom Solomon

^*Corresponding author for this work

Virus Reference Department General

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Abstract

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 1^stNovember 2015 and 1^stJune 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.

Original language	English
Article number	e0006212
Journal	PLoS Neglected Tropical Diseases
Volume	12
Issue number	2
DOIs	https://doi.org/10.1371/journal.pntd.0006212
Publication status	Published - 12 Feb 2018

Bibliographical note

Funding Information:
This work was supported by the United Kingdom Medical Research Council (https://www.mrc.ac.uk/, Grant number MC_PC_15096); the National Institute for Health Research Health Protection Research Unit (NIHR HPRU, http://www.hpruezi.nihr.ac.uk/) in Emerging and Zoonotic Infections at the University of Liverpool, in partnership with Public Health England (PHE) and Liverpool School of Tropical Medicine (LSTM); and the European Union’s Horizon 2020 research and innovation program under grant agreement No. 734584 (https://ec.europa.eu/programmes/horizon2020/). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health or Public Health England. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We would like to thank staff at the Fiocruz Flavivirus Reference Laboratory, in particular Angelica Mares-Guia, Ronaldo Lopes, Aline da Silva Santos, Cintia Damasceno, Maria Celeste Torres, Flavia Levy, Simone Sampaio, Eliane Araujo, Sheila Cheles, Marcos Cesar Lima de Mendonça and Marilda Siqueira for their ceaseless support.

Publisher Copyright:
© 2018 Mehta et al.

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Mehta, R., Soares, C. N., Medialdea-Carrera, R., Ellul, M., da Silva, M. T. T., Rosala-Hallas, A., Jardim, M. R., Burnside, G., Pamplona, L., Bhojak, M., Manohar, R., da Silva, G. A. M., Adriano, M. V., Brasil, P., Nogueira, R. M. R., Dos Santos, C. C., Turtle, L., de Sequeira, P. C., Brown, D., ... Solomon, T. (2018). The spectrum of neurological disease associated with Zika and chikungunya viruses in adults in Rio de Janeiro, Brazil: A case series. PLoS Neglected Tropical Diseases, 12(2), [e0006212]. https://doi.org/10.1371/journal.pntd.0006212

@article{0e39f1bc6105478a83eb76667f804f0d,

title = "The spectrum of neurological disease associated with Zika and chikungunya viruses in adults in Rio de Janeiro, Brazil: A case series",

abstract = "Background: During 2015–16 Brazil experienced the largest epidemic of Zika virus ever reported. This arthropod-borne virus (arbovirus) has been linked to Guillain-Barr{\'e} 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 1stNovember 2015 and 1stJune 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.",

author = "Ravi Mehta and Soares, {Cristiane Nascimento} and Raquel Medialdea-Carrera and Mark Ellul and {da Silva}, {Marcus Tulius Texeira} and Anna Rosala-Hallas and Jardim, {Marcia Rodrigues} and Girvan Burnside and Luciana Pamplona and Maneesh Bhojak and Radhika Manohar and {da Silva}, {Gabriel Amorelli Medeiros} and Adriano, {Marcus Vinicius} and Patricia Brasil and Nogueira, {Rita Maria Ribeiro} and {Dos Santos}, {Carolina Cardoso} and Lance Turtle and {de Sequeira}, {Patricia Carvalho} and David Brown and Griffiths, {Michael J.} and {de Filippis}, {Ana Maria Bispo} and Tom Solomon",

note = "Funding Information: This work was supported by the United Kingdom Medical Research Council (https://www.mrc.ac.uk/, Grant number MC_PC_15096); the National Institute for Health Research Health Protection Research Unit (NIHR HPRU, http://www.hpruezi.nihr.ac.uk/) in Emerging and Zoonotic Infections at the University of Liverpool, in partnership with Public Health England (PHE) and Liverpool School of Tropical Medicine (LSTM); and the European Union{\textquoteright}s Horizon 2020 research and innovation program under grant agreement No. 734584 (https://ec.europa.eu/programmes/horizon2020/). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health or Public Health England. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We would like to thank staff at the Fiocruz Flavivirus Reference Laboratory, in particular Angelica Mares-Guia, Ronaldo Lopes, Aline da Silva Santos, Cintia Damasceno, Maria Celeste Torres, Flavia Levy, Simone Sampaio, Eliane Araujo, Sheila Cheles, Marcos Cesar Lima de Mendon{\c c}a and Marilda Siqueira for their ceaseless support. Publisher Copyright: {\textcopyright} 2018 Mehta et al.",

year = "2018",

month = feb,

day = "12",

doi = "10.1371/journal.pntd.0006212",

language = "English",

volume = "12",

journal = "PLoS Neglected Tropical Diseases",

issn = "1935-2727",

publisher = "Public Library of Science",

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Mehta, R, Soares, CN, Medialdea-Carrera, R, Ellul, M, da Silva, MTT, Rosala-Hallas, A, Jardim, MR, Burnside, G, Pamplona, L, Bhojak, M, Manohar, R, da Silva, GAM, Adriano, MV, Brasil, P, Nogueira, RMR, Dos Santos, CC, Turtle, L, de Sequeira, PC, Brown, D, Griffiths, MJ, de Filippis, AMB & Solomon, T 2018, 'The spectrum of neurological disease associated with Zika and chikungunya viruses in adults in Rio de Janeiro, Brazil: A case series', PLoS Neglected Tropical Diseases, vol. 12, no. 2, e0006212. https://doi.org/10.1371/journal.pntd.0006212

TY - JOUR

T1 - The spectrum of neurological disease associated with Zika and chikungunya viruses in adults in Rio de Janeiro, Brazil

T2 - A case series

AU - Mehta, Ravi

AU - Soares, Cristiane Nascimento

AU - Medialdea-Carrera, Raquel

AU - Ellul, Mark

AU - da Silva, Marcus Tulius Texeira

AU - Rosala-Hallas, Anna

AU - Jardim, Marcia Rodrigues

AU - Burnside, Girvan

AU - Pamplona, Luciana

AU - Bhojak, Maneesh

AU - Manohar, Radhika

AU - da Silva, Gabriel Amorelli Medeiros

AU - Adriano, Marcus Vinicius

AU - Brasil, Patricia

AU - Nogueira, Rita Maria Ribeiro

AU - Dos Santos, Carolina Cardoso

AU - Turtle, Lance

AU - de Sequeira, Patricia Carvalho

AU - Brown, David

AU - Griffiths, Michael J.

AU - de Filippis, Ana Maria Bispo

AU - Solomon, Tom

N1 - Funding Information: This work was supported by the United Kingdom Medical Research Council (https://www.mrc.ac.uk/, Grant number MC_PC_15096); the National Institute for Health Research Health Protection Research Unit (NIHR HPRU, http://www.hpruezi.nihr.ac.uk/) in Emerging and Zoonotic Infections at the University of Liverpool, in partnership with Public Health England (PHE) and Liverpool School of Tropical Medicine (LSTM); and the European Union’s Horizon 2020 research and innovation program under grant agreement No. 734584 (https://ec.europa.eu/programmes/horizon2020/). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health or Public Health England. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We would like to thank staff at the Fiocruz Flavivirus Reference Laboratory, in particular Angelica Mares-Guia, Ronaldo Lopes, Aline da Silva Santos, Cintia Damasceno, Maria Celeste Torres, Flavia Levy, Simone Sampaio, Eliane Araujo, Sheila Cheles, Marcos Cesar Lima de Mendonça and Marilda Siqueira for their ceaseless support. Publisher Copyright: © 2018 Mehta et al.

PY - 2018/2/12

Y1 - 2018/2/12

N2 - 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 1stNovember 2015 and 1stJune 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.

AB - 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 1stNovember 2015 and 1stJune 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.

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U2 - 10.1371/journal.pntd.0006212

DO - 10.1371/journal.pntd.0006212

M3 - Article

C2 - 29432457

AN - SCOPUS:85044395544

SN - 1935-2727

VL - 12

JO - PLoS Neglected Tropical Diseases

JF - PLoS Neglected Tropical Diseases

IS - 2

M1 - e0006212

ER -

The spectrum of neurological disease associated with Zika and chikungunya viruses in adults in Rio de Janeiro, Brazil: A case series

Abstract

Bibliographical note

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