Origin of the São Paulo Yellow Fever epidemic of 2017–2018 revealed through molecular epidemiological analysis of fatal cases

Abstract

The largest outbreak of yellow fever of the 21st century in the Americas began in 2016, with intense circulation in the southeastern states of Brazil, particularly in sylvatic environments near densely populated areas including the metropolitan region of São Paulo city (MRSP) during 2017–2018. Herein, we describe the origin and molecular epidemiology of yellow fever virus (YFV) during this outbreak inferred from 36 full genome sequences taken from individuals who died following infection with zoonotic YFV. Our analysis revealed that these deaths were due to three genetic variants of sylvatic YFV that belong the South American I genotype and that were related to viruses previously isolated in 2017 from other locations in Brazil (Minas Gerais, Espírito Santo, Bahia and Rio de Janeiro states). Each variant represented an independent virus introduction into the MRSP. Phylogeographic and geopositioning analyses suggested that the virus moved around the peri-urban area without detectable human-to-human transmission, and towards the Atlantic rain forest causing human spill-over in nearby cities, yet in the absence of sustained viral transmission in the urban environment.

Possible non-sylvatic transmission of yellow fever between non-human primates in São Paulo city, Brazil, 2017–2018

“…It is an anthropophilic opportunistic mosquito that feeds on birds, humans, and NHP 32 . Other entomological surveys have demonstrated YFV-positive pools in Rio de Janeiro and Bahia 15 . More recently, one YFV-positive pool of Ae.…”

“…Whole genome sequences from NHP and humans from São Paulo previously generated 15 , 16 were aligned with YFV sequences from the 2016–2018 Brazilian outbreak using MAFFT (available at https://mafft.cbrc.jp/alignment/server/ ) and maximum likelihood (ML) phylogenetic analyses were conducted with a TN93 model with gamma variation 17 (available at https://www.atgc-montpellier.fr/ ). Tree was edited using FigTree v.14.3 with a mid-point root.…”

Survey on Non-Human Primates and Mosquitoes Does not Provide Evidences of Spillover/Spillback between the Urban and Sylvatic Cycles of Yellow Fever and Zika Viruses Following Severe Outbreaks in Southeast Brazil

“…This finding, together with epidemiological, genetic and entomological records obtained during the outbreak [34,[42][43][44][45][46], reinforced the sylvatic nature of the outbreak and the absence of spillover. Briefly, the demographic characteristics of the infected humans [43,46] and the spread rates of YFV over time and space and the genetic clades found in phylogeographic analyses were consistent with an NHP-sylvatic mosquitoes-human transmission [3,44,45,47,48]. Furthermore, all investigated cases also shared ecological conditions indicating their sylvatic origin, such as contact with forested areas, including people that entered into the jungle or live in the interface between cities and the natural environment [3,49,50].…”

Vaccination and Therapeutics: Responding to the Changing Epidemiology of Yellow Fever

“…This led to an exponential increase in transmission leading to over 2000 confirmed cases and over 600 deaths. Molecular analysis confirmed that the 2016-2017 epidemic strain was within the South American (SA) 1 genotype and that the epidemic resulted from direct sylvatic spillover to humans with the absence of sustained YFV transmission within the urban cycle [19,32,33]. Some studies have attributed the 2016 YF epidemic in YF non-endemic regions of Brazil to increased virulence of the new virus strain [31,32,34]; others have blamed changing aspects of population and ecology, such as the rise in population density [34], the geographical expansion of the peri-urban mosquito Aedes albopictus [35], human encroachment into NHP habitats [36], and global warming [37].…”