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.

Highlights

  • In 2014, intense enzootic activity of yellow fever virus (YFV) was detected in Mato Grosso do Sul and Goiás states that adjoin the Amazon region of Brazil[15,16]

  • Among all patients who died with suspected YFV infection between December 2017 and April 2018, we focused on 81 cases identified through the service of verification of deaths of the capital - USP (SVOC-USP) in the city of São Paulo (Fig. 1A)

  • We describe the outbreak of YFV in the metropolitan region of São Paulo city (MRSP), Brazil, in 2016–2018, its origin and how the virus diversified and moved around the largest conurbation in the southern hemisphere carried by non-human primates (NHPs), killing 176 people during 2018 in the process[45]

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Summary

Introduction

In 2014, intense enzootic activity of YFV was detected in Mato Grosso do Sul and Goiás states that adjoin the Amazon region of Brazil[15,16]. A peak of notified human cases was reached in January 201823 This was the largest outbreak registered in 21st century in the most populated state of Brazil, including the densely populated metropolitan region of São Paulo city (MRSP), which is the largest conurbation in the southern hemisphere with around 23 million inhabitants. Vaccination was extended to the whole urban population as well as to all inhabitants of the São Paulo state as the epidemic expanded[22] As this is the first time in the 21st century that cases of YFV have appeared in the MRSP, we sought to characterize the circulating viruses and establish their origin by studying their evolution and phylogeography based on samples taken from patients who died during the 2017–2018 outbreak

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