Caracterização molecular dos arbovírus identificados em pacientes com doença febril aguda e doença neurológica infecciosa na região Centro-Sul de Mato Grosso, Brasil

Abstract

Arboviruses remain a major public health problem worldwide. The State of Mato Grosso is one of the states most affected by diseases caused by arbovirus in Brazil. The present study aimed to perform a molecular description of Chikungunya (CHIKV), Dengue 4 (DENV-4) and Oropouche (OROV) after high-throughput sequencing of liquor and isolates obtained from neurological cases in 2019 and acute febrile cases in 2012, respectively, in the South-Center region of Mato Grosso State. Chapter 1 reports six cases of neurological infection, five diagnosed as viral encephalitis and one as acute meningitis, mostly in women with average age of 24 years. CHIKV ECSA genotype (10,834-11,804 nt) was identified in the six cases; one of the cases presented co-infection with DENV-4 genotype II (874 nt) and OROV (segment S) genotype IA (302 nt). The most frequent symptoms of these patients were headache and fever, in 83% and 50%, respectively. The meningitis case evolved to death due to the severity of the clinical condition, and the neonatal case with a maternal history of self-limited febrile illness in the last trimester of pregnancy, presented sequelae such as nystagmus, strabismus and partial bilateral hearing loss. Chapter 2 is based on a molecular characterization of DENV-4 in isolates from an outbreak in 2012 in the state of Mato Grosso. The 26 cases of DENV-4 developed acute febrile disease without alarm signs in 73.1% and with alarm signs in 26.9%, one case had coagulation disorders. The 26 complete genomic sequences belong to genotype II of DENV-4 forming two lineages, getting closer to sequences identified in the state of Roraima in 2010. The mutation profile determined that these isolates have a nucleotide and amino acid identity of 99.8% and 99.5%, respectively; 6,019 point mutations were identified, 88.75% were synonymous and 11.75% were non synonymous. The structural gene with most amino acid variation was the envelope protein, and the non-structural gene was the NS2A protein. These genes are the main target of host neutralizing antibodies and a virulence factor, respectively. Molecular analysis of these arboviruses helps to understand how variations can lead to alterations on virus fitness, vector competence, pathogenesis and virulence in their hosts.