Fatal outcome of chikungunya virus infection in Brazil

Federal University of Ceará. Fortaleza, CE, Brazil / Central Public Health Laboratory of Ceará State. Fortaleza, CE, Brazil.University of São Paulo. Virology Research Center. Ribeirão Preto, SP, Brazil.Federal University of Ceará. Fortaleza, CE, Brazil.University of Oxford. Department of Zoology. oxford, United Kingdom.University of São Paulo. Virology Research Center. Ribeirão Preto, SP, Brazil.University of Oxford. Department of Zoology. oxford, United Kingdom / Gorgas Memorial Institute of Health Studies. Department of Research in Virology and Biotechnology. Panama City, Panama.Central Public Health Laboratory of Ceará State. Fortaleza, CE, Brazil.Central Public Health Laboratory of Ceará State. Fortaleza, CE, Brazil / Centro Universitário Christus. Faculdade de Medicina. Fortaleza, CE, Brazil.Central Public Health Laboratory of Ceará State. Fortaleza, CE, Brazil.Federal University of Ceará. Fortaleza, CE, Brazil.State Health Secretariat of Ceará. Death Verification Service Dr Rocha Furtado. Fortaleza, CE, Brazil.Federal University of Ceará. Fortaleza, CE, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Federal University of Ceará. Fortaleza, CE, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Centro Universitário Christus. Faculdade de Medicina. Fortaleza, CE, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Centro Universitário Christus. Faculdade de Medicina. Fortaleza, CE, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Centro Universitário Christus. Faculdade de Medicina. Fortaleza, CE, Brazil.Centro Universitário Christus. Faculdade de Medicina. Fortaleza, CE, Brazil.Centro Universitário Christus. Faculdade de Medicina. Fortaleza, CE, Brazil.Federal University of Ceará. Fortaleza, CE, Brazil.Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil / Ministry of Health. Brasilia, DF, Brazil.Ministry of Health. Brasilia, DF, Brazil.Ministry of Health. Brasilia, DF, Brazil.Ministry of Health. Brasilia, DF, Brazil.Faculdade de Medicina São Leopoldo Mandic. Campinas, SP, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.University of Oxford. Department of Zoology. Oxford, United Kingdom.University of São Paulo. Virology Research Center. Ribeirão Preto, SP, Brazil.University of Oxford. Department of Zoology. Oxford, United Kingdom / Imperial College London. Department of Infectious Disease Epidemiology. London, United Kingdom.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Federal University of Ceará. Fortaleza, CE, Brazil.Federal University of Ceará. Fortaleza, CE, Brazil / Oswaldo Cruz Foundation - Branch Ceará. Fortaleza, CE, Brazil.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. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America