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.

“Kankasha” in Kassala: A prospective observational cohort study of the clinical characteristics, epidemiology, genetic origin, and chronic impact of the 2018 epidemic of Chikungunya virus infection in Kassala, Sudan

“…[13,16] Central nervous system infections with fatal outcomes have been reported in the Americas. [20] Other locations have documented substantial rises in all-cause deaths during outbreak periods. [20][21][22][23] Hypotheses to explain these changes include persistent immune activation triggered by viral debris, improved surveillance, and genetic mutation, particularly a new variant known as the Indian Ocean Lineage (IOL) which, since the 2004-2006 pandemic, has been linked to greater severity and the highest rates of non-recovery.…”

“…[20] Other locations have documented substantial rises in all-cause deaths during outbreak periods. [20][21][22][23] Hypotheses to explain these changes include persistent immune activation triggered by viral debris, improved surveillance, and genetic mutation, particularly a new variant known as the Indian Ocean Lineage (IOL) which, since the 2004-2006 pandemic, has been linked to greater severity and the highest rates of non-recovery. [24] IOL has also been linked to increased risk of outbreak as some forms contain a mutation that allows CHIKV to use the temperate-dwelling Aedes albopictus mosquito as a vector as well the tropical Aedes aegypti.…”

“…[ 13 , 16 ] Central nervous system infections with fatal outcomes have been reported in the Americas. [ 20 ] Other locations have documented substantial rises in all-cause deaths during outbreak periods. [ 20 – 23 ]…”

“…[ 20 ] Other locations have documented substantial rises in all-cause deaths during outbreak periods. [ 20 – 23 ]…”

Viral and Prion Infections Associated with Central Nervous System Syndromes in Brazil

“…Moreover, long-term sequelae can occur after infection. During the CHIKV epidemic in Brazil, atypical and severe cases were reported, including neuronal impairment in adults and newborns (mother-to-child infection) [ 149 , 150 , 151 , 152 , 153 ].…”