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Fatal outcome of chikungunya virus infection in Brazil

Souza, William Marciel1; Lima, Shirlene Telmos Silva de2, 3; Cavalcante, John Washington4, 5; da Silva Candido, Darlan6, 7; Fumagalli, Marcilio Jorge8, 9; Carrera, Jean-Paul10, 11; Simões Mello, Leda Maria12, 13; de Carvalho Araújo, Fernanda Montenegro14, 15; Cavalcante Ramalho, Izabel Letícia16, 17; de Almeida Barreto, Francisca Kalline18, 19; de Melo Braga, Deborah Nunes20, 21; Simião, Adriana Rocha22, 23; Miranda da Silva, Mayara Jane24, 25; Oliveira, Rhaquel de Morais Alves Barbosa26, 27; Lima, Clayton Pereira Silva28, 29; Sousa Lins, Camila de30, 31; Barata, Rafael Ribeiro32, 33; Melo, Marcelo Nunes Pereira34; de Souza, Michel Platini Caldas35; Franco, Luciano Monteiro36; Távora, Fábio Rocha Fernandes37; Queiroz Lemos, Daniele Rocha38; Alencar, Carlos Henrique Morais de39; Jesus, Ronaldo de40; Souza Fonseca, Vagner de41; Dutra, Leonardo Hermes42; Abreu, André Luiz de43; Araújo, Emerson Luiz Lima44; Ribas Freitas, André Ricardo45; Gonçalves Vianez Júnior, João Lídio da Silva46; Pybus, Oliver G47; Moraes Figueiredo, Luiz Tadeu48; Faria, Nuno Rodrigues49; Teixeira Nunes, Márcio Roberto50; Góes Cavalcanti, Luciano Pamplona de51; Miyajima, Fabio52

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.