Fatal Outcome of Chikungunya Virus Infection in Brazil.


Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213

Informations de publication

Date de publication:
05 10 2021
Historique:
received: 17 07 2020
accepted: 22 07 2020
pubmed: 9 8 2020
medline: 21 10 2021
entrez: 9 8 2020
Statut: ppublish

Résumé

Chikungunya virus (CHIKV) emerged in the Americas in 2013 and has caused approximately 2.1 million cases and >600 deaths. A retrospective investigation was undertaken to describe clinical, epidemiological, and viral genomic features associated with deaths caused by CHIKV in Ceará state, northeast Brazil. Sera, cerebrospinal fluid (CSF), and tissue samples from 100 fatal cases with suspected arbovirus infection were tested for CHIKV, dengue virus (DENV), and Zika virus (ZIKV). Clinical, epidemiological, and death reports were obtained for patients with confirmed CHIKV infection. Logistic regression analysis was undertaken to identify independent factors associated with risk of death during CHIKV infection. Phylogenetic analysis was conducted using whole genomes from a subset of cases. Sixty-eight fatal cases had CHIKV infection confirmed by reverse-transcription quantitative polymerase chain reaction (52.9%), viral antigen (41.1%), and/or specific immunoglobulin M (63.2%). Co-detection of CHIKV with DENV was found in 22% of fatal cases, ZIKV in 2.9%, and DENV and ZIKV in 1.5%. A total of 39 CHIKV deaths presented with neurological signs and symptoms, and CHIKV-RNA was found in the CSF of 92.3% of these patients. Fatal outcomes were associated with irreversible multiple organ dysfunction syndrome. Patients with diabetes appear to die at a higher frequency during the subacute phase. Genetic analysis showed circulation of 2 CHIKV East-Central-South African (ECSA) lineages in Ceará and revealed no unique virus genomic mutation associated with fatal outcome. The investigation of the largest cross-sectional cohort of CHIKV deaths to date reveals that CHIKV-ECSA strains can cause death in individuals from both risk and nonrisk groups, including young adults.

Sections du résumé

BACKGROUND
Chikungunya virus (CHIKV) emerged in the Americas in 2013 and has caused approximately 2.1 million cases and >600 deaths. A retrospective investigation was undertaken to describe clinical, epidemiological, and viral genomic features associated with deaths caused by CHIKV in Ceará state, northeast Brazil.
METHODS
Sera, cerebrospinal fluid (CSF), and tissue samples from 100 fatal cases with suspected arbovirus infection were tested for CHIKV, dengue virus (DENV), and Zika virus (ZIKV). Clinical, epidemiological, and death reports were obtained for patients with confirmed CHIKV infection. Logistic regression analysis was undertaken to identify independent factors associated with risk of death during CHIKV infection. Phylogenetic analysis was conducted using whole genomes from a subset of cases.
RESULTS
Sixty-eight fatal cases had CHIKV infection confirmed by reverse-transcription quantitative polymerase chain reaction (52.9%), viral antigen (41.1%), and/or specific immunoglobulin M (63.2%). Co-detection of CHIKV with DENV was found in 22% of fatal cases, ZIKV in 2.9%, and DENV and ZIKV in 1.5%. A total of 39 CHIKV deaths presented with neurological signs and symptoms, and CHIKV-RNA was found in the CSF of 92.3% of these patients. Fatal outcomes were associated with irreversible multiple organ dysfunction syndrome. Patients with diabetes appear to die at a higher frequency during the subacute phase. Genetic analysis showed circulation of 2 CHIKV East-Central-South African (ECSA) lineages in Ceará and revealed no unique virus genomic mutation associated with fatal outcome.
CONCLUSIONS
The investigation of the largest cross-sectional cohort of CHIKV deaths to date reveals that CHIKV-ECSA strains can cause death in individuals from both risk and nonrisk groups, including young adults.

Identifiants

pubmed: 32766829
pii: 5885158
doi: 10.1093/cid/ciaa1038
pmc: PMC8492446
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2436-e2443

Subventions

Organisme : Brazilian National Council for Scientific and Technological Development
ID : 302584/2015-3
Organisme : Medical Research Council
ID : MR/S019510/1
Pays : United Kingdom
Organisme : Wellcome Trust and Royal Society Sir Henry Dale Fellowship
ID : 204311/Z/16/Z
Organisme : Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico
Organisme : Brazilian National Council for Scientific and Technological Development
ID : 408338/2018-0
Organisme : São Paulo Research Foundation
ID : 2017/13981-0
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R015600/1
Pays : United Kingdom

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

Auteurs

Shirlene Telmos Silva de Lima (STS)

Federal University of Ceará, Fortaleza, Brazil.
Central Public Health Laboratory of Ceará State, Fortaleza, Brazil.

William Marciel de Souza (WM)

Virology Research Center, University of São Paulo, Ribeirão Preto, Brazil.

John Washington Cavalcante (JW)

Federal University of Ceará, Fortaleza, Brazil.

Darlan da Silva Candido (D)

Department of Zoology, University of Oxford, Oxford, United Kingdom.

Marcilio Jorge Fumagalli (MJ)

Virology Research Center, University of São Paulo, Ribeirão Preto, Brazil.

Jean-Paul Carrera (JP)

Department of Zoology, University of Oxford, Oxford, United Kingdom.
Department of Research in Virology and Biotechnology, Gorgas Memorial Institute of Health Studies, Panama City, Panama.

Leda Maria Simões Mello (LM)

Central Public Health Laboratory of Ceará State, Fortaleza, Brazil.

Fernanda Montenegro De Carvalho Araújo (FM)

Central Public Health Laboratory of Ceará State, Fortaleza, Brazil.
Faculdade de Medicina do Centro Universitário Christus, Fortaleza, Ceará, Brazil.

Izabel Letícia Cavalcante Ramalho (IL)

Central Public Health Laboratory of Ceará State, Fortaleza, Brazil.

Francisca Kalline de Almeida Barreto (FK)

Federal University of Ceará, Fortaleza, Brazil.

Deborah Nunes de Melo Braga (DN)

Death Verification Service Dr Rocha Furtado, State Health Secretariat of Ceará, Fortaleza, Ceará, Brazil.

Adriana Rocha Simião (AR)

Federal University of Ceará, Fortaleza, Brazil.

Mayara Jane Miranda da Silva (MJ)

Evandro Chagas Institute, Ministry of Health, Ananindeua, Brazil.

Rhaquel de Morais Alves Barbosa Oliveira (RM)

Federal University of Ceará, Fortaleza, Brazil.

Clayton Pereira Silva Lima (CPS)

Evandro Chagas Institute, Ministry of Health, Ananindeua, Brazil.

Camila de Sousa Lins (C)

Faculdade de Medicina do Centro Universitário Christus, Fortaleza, Ceará, Brazil.

Rafael Ribeiro Barata (RR)

Evandro Chagas Institute, Ministry of Health, Ananindeua, Brazil.

Marcelo Nunes Pereira Melo (MN)

Faculdade de Medicina do Centro Universitário Christus, Fortaleza, Ceará, Brazil.

Michel Platini Caldas de Souza (MP)

Evandro Chagas Institute, Ministry of Health, Ananindeua, Brazil.

Luciano Monteiro Franco (LM)

Faculdade de Medicina do Centro Universitário Christus, Fortaleza, Ceará, Brazil.

Fábio Rocha Fernandes Távora (FR)

Faculdade de Medicina do Centro Universitário Christus, Fortaleza, Ceará, Brazil.

Daniele Rocha Queiroz Lemos (DR)

Faculdade de Medicina do Centro Universitário Christus, Fortaleza, Ceará, Brazil.

Carlos Henrique Morais de Alencar (CHM)

Federal University of Ceará, Fortaleza, Brazil.

Ronaldo de Jesus (R)

Universidade Federal de Minas Gerais, Brazil.

Vagner de Souza Fonseca (V)

Universidade Federal de Minas Gerais, Brazil.
Ministry of Health, Brasilia, Brazil.

Leonardo Hermes Dutra (LH)

Ministry of Health, Brasilia, Brazil.

André Luiz de Abreu (AL)

Ministry of Health, Brasilia, Brazil.

Emerson Luiz Lima Araújo (EL)

Ministry of Health, Brasilia, Brazil.

André Ricardo Ribas Freitas (AR)

Faculdade de Medicina São Leopoldo Mandic, Campinas, São Paulo, Brazil.

João Lídio da Silva Gonçalves Vianez Júnior (JLDSG)

Evandro Chagas Institute, Ministry of Health, Ananindeua, Brazil.

Oliver G Pybus (OG)

Department of Zoology, University of Oxford, Oxford, United Kingdom.

Luiz Tadeu Moraes Figueiredo (LTM)

Virology Research Center, University of São Paulo, Ribeirão Preto, Brazil.

Nuno Rodrigues Faria (NR)

Department of Zoology, University of Oxford, Oxford, United Kingdom.
Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.

Márcio Roberto Teixeira Nunes (MRT)

Evandro Chagas Institute, Ministry of Health, Ananindeua, Brazil.

Luciano Pamplona de Góes Cavalcanti (LPG)

Federal University of Ceará, Fortaleza, Brazil.

Fabio Miyajima (F)

Federal University of Ceará, Fortaleza, Brazil.
Oswaldo Cruz Foundation (Fiocruz), Branch Ceará, Eusebio, Brazil.

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Classifications MeSH