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GENOMIC SURVEILLANCE OF YELLOW FEVER VIRUS EPIZOOTIC IN SÃO PAULO, BRAZIL, 2016 – 2018
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Abstract
São Paulo, a densely inhabited state in southeast Brazil that contains the fourth most populated
city in the world, recently experienced its largest yellow fever virus (YFV) outbreak in
decades. YFV does not normally circulate extensively in São Paulo, so most people were
unvaccinated when the outbreak began. Surveillance in non-human primates (NHPs) is
important for determining the magnitude and geographic extent of an epizootic, thereby
helping to evaluate the risk of YFV spillover to humans. Data from infected NHPs can give
more accurate insights into YFV spread than when using data from human cases alone. To
contextualise human cases, identify epizootic foci and uncover the rate and direction of YFV
spread in São Paulo, we generated and analysed virus genomic data and epizootic case
data from NHPs in São Paulo. We report the occurrence of three spatiotemporally distinct
phases of the outbreak in São Paulo prior to February 2018. We generated 51 new virus
genomes from YFV positive cases identified in 23 different municipalities in São Paulo,
mostly sampled from NHPs between October 2016 and January 2018. Although we observe
substantial heterogeneity in lineage dispersal velocities between phylogenetic branches,
continuous phylogeographic analyses of generated YFV genomes suggest that YFV lineages spread in São Paulo at a mean rate of approximately 1km per day during all phases
of the outbreak. Viral lineages from the first epizootic phase in northern São Paulo subsequently
dispersed towards the south of the state to cause the second and third epizootic
phases there. This alters our understanding of how YFV was introduced into the densely
populated south of São Paulo state. Our results shed light on the sylvatic transmission of
YFV in highly fragmented forested regions in São Paulo state and highlight the importance
of continued surveillance of zoonotic pathogens in sentinel species.
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