Abstract
The current outbreak of yellow fever virus (YFV) that is afflicting Brazil since the end of 2016 probably originated from a re-introduction of YFV from endemic areas into the non-endemic Southeastern Brazil. However, the lack of genomic sequences from endemic regions hinders the tracking of YFV’s dissemination routes. We assessed the origin and spread of the ongoing YFV Brazilian outbreak analyzing a new set of YFV strains infecting humans, non-human primates (NHPs) and mosquitoes sampled across five Brazilian states from endemic and non-endemic regions between 2015 and 2018. We found two YFV sub-clade 1E lineages circulating in NHP from Goiás state (GO), resulting from independent viral introductions into the Araguaia tributary river basin: while one strain from 2017 clustered intermingled with Venezuelan YFV strains from 2000, the other YFV strains sampled in 2015 and 2017 clustered with sequences of the current YFV outbreak in the Brazilian Southeastern region (named YFV2015-2018 lineage), displaying the same molecular signature associated to the current YFV outbreak. After its introduction in GO at around mid-2014, the YFV2015-2018 lineage followed two paths of dissemination outside GO, originating two major YFV sub-lineages: (1) the YFVMG/ES/RJ sub-lineage spread sequentially from the eastern area of Minas Gerais state to Espírito Santo and then to Rio de Janeiro states, following the Southeast Atlantic basin; (2) the YFVMG/SP sub-lineage spread from the southwestern area of Minas Gerais to the metropolitan region of São Paulo state, following the Paraná basin. These results indicate the ongoing YFV outbreak in Southeastern Brazil originated from a dissemination event from GO almost 2 years before its recognition at the end of 2016. From GO this lineage was introduced in Minas Gerais state at least two times, originating two sub-lineages that followed different routes toward densely populated areas. The spread of YFV outside endemic regions for at least 4 years stresses the imperative importance of the continuous monitoring of YFV to aid decision-making for effective control policies aiming the increase of vaccination coverage to avoid the YFV transmission in densely populated urban centers.
Highlights
In Brazil, the yellow fever virus (YFV) have been sporadically detected in human and non-human primates (NHPs) populations from the enzootic/endemic Northern (Amazon) and epidemic Central-Western regions during the second half of the 20th century (Carrington and Auguste, 2013; Monath and Vasconcelos, 2015)
38 cases and nine deaths have been reported in January 2019, around 1,160 km from the first signal of increased incidence of YF in the Southeast in late 2016 (Secretaria de Vigilância em Saúde, 2019)
Previous studies pointed out that the ongoing YFV outbreak in the Brazilian Southeastern region resulted from a single introduction event of a YFV Modern lineage strain from an endemic area (Mir et al, 2017; Faria et al, 2018; Gomez et al, 2018; Rezende et al, 2018)
Summary
In Brazil, the yellow fever virus (YFV) have been sporadically detected in human and non-human primates (NHPs) populations from the enzootic/endemic Northern (Amazon) and epidemic Central-Western regions during the second half of the 20th century (Carrington and Auguste, 2013; Monath and Vasconcelos, 2015). Sequential YF outbreaks reported in the Southeastern and Southern Brazilian regions in 2000–2001, 2008–2009 and 2016–2018 were more likely caused by single independent events of re-introduction of YFV strains from endemic areas (Mir et al, 2017). A recent study speculated that the YFV strain causing the current outbreak would have been originated in the Brazilian Central-West region. This conjecture was based on the date of the most recent common ancestor of the 2016–2018 Brazilian YFV, which was estimated in a period (July 2014 to January 2016) when YFV circulation was reported in the state of Goiás (Central-Western region; Rezende et al, 2018). The precise routes of dissemination of YFV strains from endemic to non-endemic areas observed in Brazil in the last 15–20 years are difficult to elucidate because of the scarcity of sequences sampled from endemic regions in that period
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