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January 05, 2016; 86 (1) Article

Chikungunya virus–associated encephalitis

A cohort study on La Réunion Island, 2005–2009

Patrick Gérardin, Thérèse Couderc, Marc Bintner, Patrice Tournebize, Michel Renouil, Jérome Lémant, Véronique Boisson, Gianandrea Borgherini, Frédérik Staikowsky, Frédéric Schramm, Marc Lecuit, Alain Michault
First published November 25, 2015, DOI: https://doi.org/10.1212/WNL.0000000000002234
Patrick Gérardin
From the Centre Hospitalier Universitaire (CHU) (P.G., M.B., P.T., M.R., J.L., V.B., G.B., A.M.) and Centre d'Investigation Clinique–Épidémiologie Clinique (CIC1410) de La Réunion (Inserm, CHU, Université de La Réunion, Union Régionale des Médecins Libéraux de la Réunion) (P.G.), Saint Pierre, La Réunion; UMR PIMIT (Inserm U 1187, CNRS 9192, IRD 249, Université de La Réunion) (P.G., A.M.), CYROI, Saint-Denis, La Réunion; Biology of Infection Unit (T.C., M.L.), Institut Pasteur, Paris; Inserm U1117 (T.C., M.L.), Paris; CHU Henri Mondor (F. Staikowsky), Créteil; Université de Strasbourg (F. Schramm), EA 7290, Faculté de Médecine, Strasbourg; and Université Paris Descartes (M.L.), Sorbonne Paris Cité, Division of Infectious Diseases and Tropical Medicine, Necker Enfants Malades University Hospital, Institut Imagine (M.L.), Paris, France.
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Thérèse Couderc
From the Centre Hospitalier Universitaire (CHU) (P.G., M.B., P.T., M.R., J.L., V.B., G.B., A.M.) and Centre d'Investigation Clinique–Épidémiologie Clinique (CIC1410) de La Réunion (Inserm, CHU, Université de La Réunion, Union Régionale des Médecins Libéraux de la Réunion) (P.G.), Saint Pierre, La Réunion; UMR PIMIT (Inserm U 1187, CNRS 9192, IRD 249, Université de La Réunion) (P.G., A.M.), CYROI, Saint-Denis, La Réunion; Biology of Infection Unit (T.C., M.L.), Institut Pasteur, Paris; Inserm U1117 (T.C., M.L.), Paris; CHU Henri Mondor (F. Staikowsky), Créteil; Université de Strasbourg (F. Schramm), EA 7290, Faculté de Médecine, Strasbourg; and Université Paris Descartes (M.L.), Sorbonne Paris Cité, Division of Infectious Diseases and Tropical Medicine, Necker Enfants Malades University Hospital, Institut Imagine (M.L.), Paris, France.
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Marc Bintner
From the Centre Hospitalier Universitaire (CHU) (P.G., M.B., P.T., M.R., J.L., V.B., G.B., A.M.) and Centre d'Investigation Clinique–Épidémiologie Clinique (CIC1410) de La Réunion (Inserm, CHU, Université de La Réunion, Union Régionale des Médecins Libéraux de la Réunion) (P.G.), Saint Pierre, La Réunion; UMR PIMIT (Inserm U 1187, CNRS 9192, IRD 249, Université de La Réunion) (P.G., A.M.), CYROI, Saint-Denis, La Réunion; Biology of Infection Unit (T.C., M.L.), Institut Pasteur, Paris; Inserm U1117 (T.C., M.L.), Paris; CHU Henri Mondor (F. Staikowsky), Créteil; Université de Strasbourg (F. Schramm), EA 7290, Faculté de Médecine, Strasbourg; and Université Paris Descartes (M.L.), Sorbonne Paris Cité, Division of Infectious Diseases and Tropical Medicine, Necker Enfants Malades University Hospital, Institut Imagine (M.L.), Paris, France.
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Patrice Tournebize
From the Centre Hospitalier Universitaire (CHU) (P.G., M.B., P.T., M.R., J.L., V.B., G.B., A.M.) and Centre d'Investigation Clinique–Épidémiologie Clinique (CIC1410) de La Réunion (Inserm, CHU, Université de La Réunion, Union Régionale des Médecins Libéraux de la Réunion) (P.G.), Saint Pierre, La Réunion; UMR PIMIT (Inserm U 1187, CNRS 9192, IRD 249, Université de La Réunion) (P.G., A.M.), CYROI, Saint-Denis, La Réunion; Biology of Infection Unit (T.C., M.L.), Institut Pasteur, Paris; Inserm U1117 (T.C., M.L.), Paris; CHU Henri Mondor (F. Staikowsky), Créteil; Université de Strasbourg (F. Schramm), EA 7290, Faculté de Médecine, Strasbourg; and Université Paris Descartes (M.L.), Sorbonne Paris Cité, Division of Infectious Diseases and Tropical Medicine, Necker Enfants Malades University Hospital, Institut Imagine (M.L.), Paris, France.
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Michel Renouil
From the Centre Hospitalier Universitaire (CHU) (P.G., M.B., P.T., M.R., J.L., V.B., G.B., A.M.) and Centre d'Investigation Clinique–Épidémiologie Clinique (CIC1410) de La Réunion (Inserm, CHU, Université de La Réunion, Union Régionale des Médecins Libéraux de la Réunion) (P.G.), Saint Pierre, La Réunion; UMR PIMIT (Inserm U 1187, CNRS 9192, IRD 249, Université de La Réunion) (P.G., A.M.), CYROI, Saint-Denis, La Réunion; Biology of Infection Unit (T.C., M.L.), Institut Pasteur, Paris; Inserm U1117 (T.C., M.L.), Paris; CHU Henri Mondor (F. Staikowsky), Créteil; Université de Strasbourg (F. Schramm), EA 7290, Faculté de Médecine, Strasbourg; and Université Paris Descartes (M.L.), Sorbonne Paris Cité, Division of Infectious Diseases and Tropical Medicine, Necker Enfants Malades University Hospital, Institut Imagine (M.L.), Paris, France.
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Jérome Lémant
From the Centre Hospitalier Universitaire (CHU) (P.G., M.B., P.T., M.R., J.L., V.B., G.B., A.M.) and Centre d'Investigation Clinique–Épidémiologie Clinique (CIC1410) de La Réunion (Inserm, CHU, Université de La Réunion, Union Régionale des Médecins Libéraux de la Réunion) (P.G.), Saint Pierre, La Réunion; UMR PIMIT (Inserm U 1187, CNRS 9192, IRD 249, Université de La Réunion) (P.G., A.M.), CYROI, Saint-Denis, La Réunion; Biology of Infection Unit (T.C., M.L.), Institut Pasteur, Paris; Inserm U1117 (T.C., M.L.), Paris; CHU Henri Mondor (F. Staikowsky), Créteil; Université de Strasbourg (F. Schramm), EA 7290, Faculté de Médecine, Strasbourg; and Université Paris Descartes (M.L.), Sorbonne Paris Cité, Division of Infectious Diseases and Tropical Medicine, Necker Enfants Malades University Hospital, Institut Imagine (M.L.), Paris, France.
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Véronique Boisson
From the Centre Hospitalier Universitaire (CHU) (P.G., M.B., P.T., M.R., J.L., V.B., G.B., A.M.) and Centre d'Investigation Clinique–Épidémiologie Clinique (CIC1410) de La Réunion (Inserm, CHU, Université de La Réunion, Union Régionale des Médecins Libéraux de la Réunion) (P.G.), Saint Pierre, La Réunion; UMR PIMIT (Inserm U 1187, CNRS 9192, IRD 249, Université de La Réunion) (P.G., A.M.), CYROI, Saint-Denis, La Réunion; Biology of Infection Unit (T.C., M.L.), Institut Pasteur, Paris; Inserm U1117 (T.C., M.L.), Paris; CHU Henri Mondor (F. Staikowsky), Créteil; Université de Strasbourg (F. Schramm), EA 7290, Faculté de Médecine, Strasbourg; and Université Paris Descartes (M.L.), Sorbonne Paris Cité, Division of Infectious Diseases and Tropical Medicine, Necker Enfants Malades University Hospital, Institut Imagine (M.L.), Paris, France.
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Gianandrea Borgherini
From the Centre Hospitalier Universitaire (CHU) (P.G., M.B., P.T., M.R., J.L., V.B., G.B., A.M.) and Centre d'Investigation Clinique–Épidémiologie Clinique (CIC1410) de La Réunion (Inserm, CHU, Université de La Réunion, Union Régionale des Médecins Libéraux de la Réunion) (P.G.), Saint Pierre, La Réunion; UMR PIMIT (Inserm U 1187, CNRS 9192, IRD 249, Université de La Réunion) (P.G., A.M.), CYROI, Saint-Denis, La Réunion; Biology of Infection Unit (T.C., M.L.), Institut Pasteur, Paris; Inserm U1117 (T.C., M.L.), Paris; CHU Henri Mondor (F. Staikowsky), Créteil; Université de Strasbourg (F. Schramm), EA 7290, Faculté de Médecine, Strasbourg; and Université Paris Descartes (M.L.), Sorbonne Paris Cité, Division of Infectious Diseases and Tropical Medicine, Necker Enfants Malades University Hospital, Institut Imagine (M.L.), Paris, France.
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Frédérik Staikowsky
From the Centre Hospitalier Universitaire (CHU) (P.G., M.B., P.T., M.R., J.L., V.B., G.B., A.M.) and Centre d'Investigation Clinique–Épidémiologie Clinique (CIC1410) de La Réunion (Inserm, CHU, Université de La Réunion, Union Régionale des Médecins Libéraux de la Réunion) (P.G.), Saint Pierre, La Réunion; UMR PIMIT (Inserm U 1187, CNRS 9192, IRD 249, Université de La Réunion) (P.G., A.M.), CYROI, Saint-Denis, La Réunion; Biology of Infection Unit (T.C., M.L.), Institut Pasteur, Paris; Inserm U1117 (T.C., M.L.), Paris; CHU Henri Mondor (F. Staikowsky), Créteil; Université de Strasbourg (F. Schramm), EA 7290, Faculté de Médecine, Strasbourg; and Université Paris Descartes (M.L.), Sorbonne Paris Cité, Division of Infectious Diseases and Tropical Medicine, Necker Enfants Malades University Hospital, Institut Imagine (M.L.), Paris, France.
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Frédéric Schramm
From the Centre Hospitalier Universitaire (CHU) (P.G., M.B., P.T., M.R., J.L., V.B., G.B., A.M.) and Centre d'Investigation Clinique–Épidémiologie Clinique (CIC1410) de La Réunion (Inserm, CHU, Université de La Réunion, Union Régionale des Médecins Libéraux de la Réunion) (P.G.), Saint Pierre, La Réunion; UMR PIMIT (Inserm U 1187, CNRS 9192, IRD 249, Université de La Réunion) (P.G., A.M.), CYROI, Saint-Denis, La Réunion; Biology of Infection Unit (T.C., M.L.), Institut Pasteur, Paris; Inserm U1117 (T.C., M.L.), Paris; CHU Henri Mondor (F. Staikowsky), Créteil; Université de Strasbourg (F. Schramm), EA 7290, Faculté de Médecine, Strasbourg; and Université Paris Descartes (M.L.), Sorbonne Paris Cité, Division of Infectious Diseases and Tropical Medicine, Necker Enfants Malades University Hospital, Institut Imagine (M.L.), Paris, France.
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Marc Lecuit
From the Centre Hospitalier Universitaire (CHU) (P.G., M.B., P.T., M.R., J.L., V.B., G.B., A.M.) and Centre d'Investigation Clinique–Épidémiologie Clinique (CIC1410) de La Réunion (Inserm, CHU, Université de La Réunion, Union Régionale des Médecins Libéraux de la Réunion) (P.G.), Saint Pierre, La Réunion; UMR PIMIT (Inserm U 1187, CNRS 9192, IRD 249, Université de La Réunion) (P.G., A.M.), CYROI, Saint-Denis, La Réunion; Biology of Infection Unit (T.C., M.L.), Institut Pasteur, Paris; Inserm U1117 (T.C., M.L.), Paris; CHU Henri Mondor (F. Staikowsky), Créteil; Université de Strasbourg (F. Schramm), EA 7290, Faculté de Médecine, Strasbourg; and Université Paris Descartes (M.L.), Sorbonne Paris Cité, Division of Infectious Diseases and Tropical Medicine, Necker Enfants Malades University Hospital, Institut Imagine (M.L.), Paris, France.
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Alain Michault
From the Centre Hospitalier Universitaire (CHU) (P.G., M.B., P.T., M.R., J.L., V.B., G.B., A.M.) and Centre d'Investigation Clinique–Épidémiologie Clinique (CIC1410) de La Réunion (Inserm, CHU, Université de La Réunion, Union Régionale des Médecins Libéraux de la Réunion) (P.G.), Saint Pierre, La Réunion; UMR PIMIT (Inserm U 1187, CNRS 9192, IRD 249, Université de La Réunion) (P.G., A.M.), CYROI, Saint-Denis, La Réunion; Biology of Infection Unit (T.C., M.L.), Institut Pasteur, Paris; Inserm U1117 (T.C., M.L.), Paris; CHU Henri Mondor (F. Staikowsky), Créteil; Université de Strasbourg (F. Schramm), EA 7290, Faculté de Médecine, Strasbourg; and Université Paris Descartes (M.L.), Sorbonne Paris Cité, Division of Infectious Diseases and Tropical Medicine, Necker Enfants Malades University Hospital, Institut Imagine (M.L.), Paris, France.
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Citation
Chikungunya virus–associated encephalitis
A cohort study on La Réunion Island, 2005–2009
Patrick Gérardin, Thérèse Couderc, Marc Bintner, Patrice Tournebize, Michel Renouil, Jérome Lémant, Véronique Boisson, Gianandrea Borgherini, Frédérik Staikowsky, Frédéric Schramm, Marc Lecuit, Alain Michault
Neurology Jan 2016, 86 (1) 94-102; DOI: 10.1212/WNL.0000000000002234

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Abstract

Objective: To estimate the cumulative incidence rate (CIR) of Chikungunya virus (CHIKV)–associated CNS disease during the La Réunion outbreak, and assess the disease burden and patient outcome after 3 years.

Methods: CHIKV-associated CNS disease was characterized retrospectively in a cohort of patients with positive CHIKV reverse transcriptase PCR or anti-CHIKV immunoglobulin M antibodies in the CSF and fulfilling International Encephalitis Consortium criteria for encephalitis or encephalopathy. Neurologic sequelae were assessed after 3 years.

Results: Between September 2005 and June 2006, 57 patients were diagnosed with CHIKV-associated CNS disease, including 24 with CHIKV-associated encephalitis, the latter corresponding to a CIR of 8.6 per 100,000 persons. Patients with encephalitis were observed at both extremes of age categories. CIR per 100,000 persons were 187 and 37 in patients below 1 year and over 65 years, respectively, both far superior to those of cumulated causes of encephalitis in the United States in these age categories. The case-fatality rate of CHIKV-associated encephalitis was 16.6% and the proportion of children discharged with persistent disabilities estimated between 30% and 45%. Beyond the neonatal period, the clinical presentation and outcomes were less severe in infants than in adults.

Conclusions: In the context of a large outbreak, CHIKV is a significant cause of CNS disease. As with other etiologies, CHIKV-associated encephalitis case distribution by age follows a U-shaped parabolic curve.

GLOSSARY

ADEM=
acute disseminated encephalomyelitis;
CHIKV=
Chikungunya virus;
CFR=
case-fatality rate;
CIR=
cumulative incidence rate;
DQ=
development quotient;
DWI=
diffusion-weighted imaging;
ECSA=
East Central South African;
IEC=
International Encephalitis Consortium;
IgM=
immunoglobulin M;
LP=
lumbar puncture;
NECACD=
nonencephalitic Chikungunya virus–associated CNS disease;
WNV=
West Nile virus

Footnotes

  • ↵† Deceased.

  • Coinvestigators of the Encephalchik Study Group are listed on the Neurology® Web site at Neurology.org.

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received February 18, 2015.
  • Accepted in final form August 31, 2015.
  • © 2015 American Academy of Neurology
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Disputes & Debates: Rapid online correspondence

  • Re:A dramatic neuroinfectious outbreak in Brazil possibly linked to Arboviruses
    • Patrick Gerardin, M.D., Ph.D., CHU Reunion, Saint Pierrepatrick.gerardin@chu-reunion.fr
    • Therese Couderc, Paris, France; Hanitra Randrianaivo, Saint Pierre, Reunion; Xavier Fritel, Poitiers, France; Marc Lecuit, Paris, France
    Submitted January 26, 2016
  • A dramatic neuroinfectious outbreak in Brazil possibly linked to Arboviruses
    • Joao R.M. Oliveira, Professor, Federal University of Pernambucojoao.ricardo@ufpe.br
    Submitted January 26, 2016
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