Fatal outcome of chikungunya virus infection in Brazil.
Lima STSD., Souza WMD., Cavalcante JW., da Silva Candido D., Fumagalli MJ., Carrera J-P., Simões Mello LM., de Carvalho Araújo FM., Cavalcante Ramalho IL., de Almeida Barreto FK., de Melo Braga DN., Simião AR., Miranda da Silva MJ., Oliveira RDMAB., Lima CPS., Sousa Lins CD., Barata RR., Melo MNP., de Souza MPC., Franco LM., Távora FRF., Queiroz Lemos DR., Alencar CHMD., Jesus RD., Souza Fonseca VD., Dutra LH., Abreu ALD., Araújo ELL., Ribas Freitas AR., Gonçalves Vianez Júnior JLDS., Pybus OG., Moraes Figueiredo LT., Faria NR., Teixeira Nunes MR., Góes Cavalcanti LPD., Miyajima F.
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.