Fatal outcome of chikungunya virus infection in Brazil

Clinical Infectious Diseases, 2020.

Authors:  Lima STS, Souza WM, Cavalcante JW, Candido DS, Fumagalli MJ, Carrera JP, Mello LMS, Araújo FMC, Ramalho ILC, Barreto FKA, Braga DNM, Simião AR, Silva MJM, Oliveira RMAB, Lima CPS, Lins CS, Barata RR, Melo MNP, Souza MPC, Franco LM, Távora FRF, Lemos DRQ, Alencar CHM, Jesus R, Fonseca V, Dutra LH, Abreu AL, Araújo ELL, Freitas ARR, Júnior JLSGV, Pybus OG, Figueiredo LTM, Faria NR, Nunes MRT, Cavalcanti LPG, Miyajima F.

Journal: Clinical Infectious Diseases,ciaa1038 DOI: https://doi.org/10.1093/cid/ciaa1038: (2020)

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.

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