Genomic epidemiology sheds light on the recent spatio-temporal dynamics of Yellow Fever virus and the spatial corridor that fueled its ongoing emergence in southern Brazil

Abstract

Despite the considerable morbidity and mortality of Yellow fever virus (YFV) infections in Brazil, as well as its widespread presence in non-human primate host, our understanding of disease outbreaks is hampered by limited viral genomic data. Determining the timing and spatial corridors of YFV spread, as well as the geographic hotspots that link the endemic north of the country with epidemic extra-Amazonian regions, are central to predicting and preventing future outbreak events and epidemics. Here, we tracked the recent spread of the virus by integrating genome sequences of new YFV infections sampled from infected non-human primates and humans with both epidemiological and vector data. Through a combination of phylogenetic and epidemiological models we reconstructed the recent transmission history of YFV within different epidemic seasons in Brazil. A suitability index based on the highly domesticated Aedes aegypti was able to capture the seasonality of reported human infections. Spatial modelling revealed spatial hotspots with both past reporting and low vaccination coverage, which coincided with many of the largest urban centres in the Southeast. Phylodynamic analysis unravelled the circulation of three distinct YFV lineages, and provided proof of the directionality of a known spatial corridor of viral spread that connects the endemic North with the extra-Amazonian basin. This study illustrates that genomics linked with field sampling of animals and humans within a One Health framework can provide new insights into the landscape of YFV transmission, augmenting traditional approaches to infectious disease surveillance and control.

The Importance of Entomo-Virological Investigation of Yellow Fever Virus to Strengthen Surveillance in Brazil

“…The three Midwest sequences, previous to the outbreak, are related to a 2015 sequence obtained from an NHP sample collected in Novo Brasil, a municipality from Goiás, located 175 km away from Jandaia. These sequences from Goiás clustered in a sister clade to the outbreak clade, confirming the already described topology of previous phylogeny positioning the NHP as related to the recent Southeast sequences [51], and could reinforce the possibility of spread from the Midwest to the Southeast [22].…”

“…The positive Hg. janthinomys pool from Cocos, in the Bahia Cerrado, on the border with Northwestern Minas Gerais, corroborates the YFV spread from Minas Gerais to Bahia and the feasibility of YFV cases occurring in the region, which has a low vaccination coverage in humans, and the presence of main vectors and susceptible NHP [ 22 ].…”

“…In a joint initiative, the AR843690 sample, a pool of Aedes albopictus mosquitoes, was sequenced using the MinION ® sequencing device (Oxford Nanopore Technologies, Oxford, Oxfordshire, UK) by the Oswaldo Cruz Foundation (FIOCRUZ). The genome assembly was also performed by FIOCRUZ following the methodology described in Giovanetti et al [ 22 ].…”

Avaliação da resposta imune humoral em indivíduos imunizados com a vacina atenuada YFV 17DD em vigência de infecção natural pelo vírus da febre amarela

“…1.2.2 Análise molecularO primeiro sequenciamento completo do YFV foi publicado por Rice e colaboradores em 1985(80). Atualmente, as cepas de YFV selvagens circulantes constituem um único sorotipo e há sete genótipos descritos (30), cinco que circulam na África, nomeados West Africa I, sendo do genótipo South America I, com três clados diferentes(81,82). Essa linhagem provavelmente se disseminou independentemente da Venezuela para a Amazônia brasileira em 2005 e foi responsável pela epidemia no sudeste brasileiro de 2008 a 2009, com oito mutações de possível importância funcional sendo investigadas(15,83).…”