Fatal Outcome of Chikungunya Virus Infection in Brazil

Shirlene Telmos Silva de Lima, William Marciel de Souza, John Washington Cavalcante, Darlan da Silva Candido, Marcilio Jorge Fumagalli, Jean Paul Carrera, Leda Maria Simões Mello, Fernanda Montenegro de Carvalho Araújo, Izabel Letícia Cavalcante Ramalho, Francisca Kalline de Almeida Barreto, Deborah Nunes de Melo Braga, Adriana Rocha Simião, Mayara Jane Miranda da Silva, Rhaquel de Morais Alves Barbosa Oliveira, Clayton Pereira Silva Lima, Camila de Sousa Lins, Rafael Ribeiro Barata, Marcelo Nunes Pereira Melo, Michel Platini Caldas de Souza, Luciano Monteiro FrancoFábio Rocha Fernandes Távora, Daniele Rocha Queiroz Lemos, Carlos Henrique Morais de Alencar, Ronaldo de Jesus, Vagner de Souza Fonseca, Leonardo Hermes Dutra, André Luiz de Abreu, Emerson Luiz Lima Araújo, André Ricardo Ribas Freitas, João Lídio da Silva Gonçalves Vianez, Oliver G. Pybus, Luiz Tadeu Moraes Figueiredo, Nuno Rodrigues Faria, Márcio Roberto Teixeira Nunes, Luciano Pamplona de Góes Cavalcanti, Fabio Miyajima

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


Background. Chikungunya virus (CHIKV) emerged in the Americas in 2013 and has caused approximately 2.1 million cases and >600 deaths. A retrospective investigation was undertaken to describe clinical, epidemiological, and viral 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 virus (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. Sixty-eight fatal cases had CHIKV infection confirmed by reverse-transcription quantitative polymerase chain reaction (52.9%), viral antigen (41.1%), and/or specific immunoglobulin M (63.2%). Co-detection of CHIKV with DENV was 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 subacute phase. Genetic analysis showed circulation of 2 CHIKV East-Central-South African (ECSA) lineages in Ceará and revealed no unique virus genomic mutation associated with fatal outcome. Conclusions. 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 nonrisk groups, including young adults.

Original languageEnglish
Pages (from-to)E2436-E2443
JournalClinical Infectious Diseases
Issue number7
StatePublished - Oct 1 2021

Bibliographical note

Publisher Copyright:
© The Author(s) 2020.


  • Alphavirus
  • arbovirus
  • arthritogenic
  • chikungunya virus
  • fatal cases

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases


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