Fatal outcome of chikungunya virus infection in Brazil

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.