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Fatal outcome of chikungunya virus infection in Brazil

Souza, William Marciel1; Lima, Shirlene Telmos Silva de2; Cavalcante, John Washington2; da Silva Candido, Darlan3; Fumagalli, Marcilio Jorge4; Carrera, Jean-Paul3; Simões Mello, Leda Maria5; de Carvalho Araújo, Fernanda Montenegro5; Cavalcante Ramalho, Izabel Letícia5; de Almeida Barreto, Francisca Kalline2; de Melo Braga, Deborah Nunes5; Simião, Adriana Rocha2; Miranda da Silva, Mayara Jane6; Oliveira, Rhaquel de Morais Alves Barbosa2; Lima, Clayton Pereira Silva6; Sousa Lins, Camila de7; Barata, Rafael Ribeiro6; Melo, Marcelo Nunes Pereira7; de Souza, Michel Platini Caldas6; Franco, Luciano Monteiro7; Távora, Fábio Rocha Fernandes7; Queiroz Lemos, Daniele Rocha7; Alencar, Carlos Henrique Morais de2; Jesus, Ronaldo de8; Souza Fonseca, Vagner de8; Dutra, Leonardo Hermes9; Abreu, André Luiz de9; Araújo, Emerson Luiz Lima9; Ribas Freitas, André Ricardo10; Gonçalves Vianez Júnior, João Lídio da Silva6; Pybus, Oliver G3; Moraes Figueiredo, Luiz Tadeu4; Faria, Nuno Rodrigues3; Teixeira Nunes, Márcio Roberto6; Góes Cavalcanti, Luciano Pamplona de2; Miyajima, Fabio2

Published Aug 07, 2020; Updated Aug 27, 2020 on Dryad. https://doi.org/10.5061/dryad.7d7wm37sm

Data files

Abstract

Abstract Background Chikungunya virus (CHIKV) emerged in the Americas in 2013 and has caused ~2.1 million cases and over 600 deaths. A retrospective investigation was undertaken to describe clinical, epidemiological and virus 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 (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 68 fatal cases had CHIKV infection confirmed by RT-qPCR (52.9%), viral antigen (41.1%), and/or specific-IgM (63.2%). Co-detection of CHIKV with DENV were 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 sub-acute phase. Genetic analysis showed circulation of two CHIKV-East Central South African (ECSA) lineages in Ceará and revealed no unique virus genomic mutation associated with fatal outcome. Conclusion 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 non-risk groups, including young adults.