Vigilância genômica de arboviroses durante os surtos epidêmicos de 2023 e 2024

Abstract

Arboviruses are characterized by their transmission through hematophagous arthropod vectors, comprising a group of different viral families of great medical and veterinary interest, mainly due to their potential to cause outbreaks and epidemics of severe diseases. Climate change and globalization facilitate the spread of vectors across various regions of the world, increasing transmission rates and epidemic outbreaks. In Brazil, important arboviruses transmitted by Aedes mosquitoes include Dengue virus (DENV), Chikungunya virus (CHIKV), and Zika virus (ZIKV). Due to the lack of specific treatments and vaccines for all arboviruses, genomic surveillance has become one of the main tools aiding in the understanding of transmission patterns, viral circulation, and evolution. In this context, we conducted viral surveillance of potential arboviruses associated with febrile syndromes in the municipality of Contagem in 2023, coinciding with an increase in DENV and CHIKV cases between epidemiological weeks 12 and 27 (March to June). Contagem, the third most populous municipality in Minas Gerais, is located in an economically important region bordering the capital, Belo Horizonte. In this study, 6,122 diagnostic tests were performed on febrile patients using multiplex molecular panels capable of identifying all arboviruses circulating in Brazil, including DENV, CHIKV, ZIKV, Mayaro (MAYV), Oropouche (OROV), Yellow Fever (YFV), West Nile (WNV), Saint Louis encephalitis (SLEV), Rocio (ROCV), Ilheus (ILHV), Cacipacore (CPCV), and Bussuquara (BSQV)viruses. Among these, 551 tests were positive for DENV, 1,564 for CHIKV, including seven cases of coinfection, while 4,007 tests were negative for the other viruses investigated. Thus, we performed genomic characterization of 246 CHIKV samples and 168 DENV samples to identify the circulating serotypes and genotypes of these two viruses, as well as dispersal patterns and introduction events. The analyses showed that all CHIKV sequences belonged to the East-Central-South African (ECSA) lineage, while the DENV sequences were classified as genotype V of serotype 1. Phylogenetic inferences revealed that CHIKV sequences clustered into four distinct clades, with specific mutations and strong statistical support, whereas DENV sequences formed five main clades, demonstrating interregional circulation for both viruses. Genomic analyses identified mutations at site 211 of the envelope glycoprotein E1 (E1-K211T/I), previously associated with increased CHIKV transmissibility, as well as other potential positively selected mutations in the nsP1, nsP2, nsP3, and nsP4 proteins. The emergence and establishment of these mutations in recent CHIKV sequences may be associated with the recent epidemic outbreaks in the study region, where the CHIKV positivity rate surpassed that of DENV, an unprecedented scenario. For DENV, possible positively selected mutations were identified in the prM, E, NS3, and NS5 proteins, whose functional impacts remain unknown. Additionally, in 2024, Brazil reported an increase in OROV cases, previously restricted to the Amazon region, raising concerns among health authorities. In this study, we also conducted nationwide viral surveillance for OROV, identifying six new genomes from the Northeast (Bahia), Southeast (Espírito Santo), and South (Santa Catarina) regions of Brazil. Our genomic analyses corroborate the previously identified genomicrearrangement patterns in the S and L segments of the virus, which may be associated with the increase in cases and its spread across Brazil, as well as recent reports of neurological outcomes and vertical transmission linked to OROV. These studies reinforce the importance of using multiplexed panels for the identification of arboviruses with similar symptoms circulating in Brazil and their integration with genomic-epidemiological surveillance to monitor viral diversity and characterize transmission patterns, providing the necessary knowledge for public health interventions