Genome Analysis of Yellow Fever Reveals Deadly Route of the Virus From Amazon to South Brazil

The deadly virus that causes yellow fever has become widespread in wild animals living in Brazil's Amazon forest. Recently, scientists discovered that the pathogen has been spreading to southeastern Brazil where it has reemerged and caused human outbreaks.

YFV Transmission Cycles in Brazil

Yellow fever virus (YFV) refers to a single-stranded RNA arbovirus that belongs to the genus Flavivirus. It is transmitted by vectors such as mosquitoes, ticks, or other arthropods. The bites of infected Aedes and Haemagogus mosquitoes usually carry out human transmission.

YFV can be maintained in two transmission cycles: jungle and urban. Known as sylvatic cycles, the jungle cycle is associated with nonhuman primates and mosquitoes that dwell in forest canopy. Meanwhile, the urban cycle involves the transmission by highly anthropophilic mosquito vectors.

In Brazil, the transmission of yellow fever historically occurs within a jungle cycle in the Amazon. The outbreaks happen with potential human infection under favorable conditions such as the emergence of viral strains, build-up of susceptible hosts, high vector density, and suitable temperature and rainfall.

In recent decades, the re-emergence events of YFV in Brazil have greatly impacted public health. There has been a spatial expansion of viral circulation in 2002-2003, 2007-2009, 2016-2019, and the ongoing outbreak from 2020 to the present. The pathogen spreads from the east toward the south region of the country, reaching the state of Rio Grande do Sul up to the extreme meridional areas.

During these outbreaks, experts have reported thousands of deaths of nonhuman primates. Additionally, over 2,100 human cases were documented in the Southeastern region of Brazil. In this area, the case fatality rate is approximately 30%, many of which were from places with low vaccination coverage.

In September 2020, a new yellow fever virus re-emergence was reported within Goiás, Distrito Federal in the midwest, and the Southeast state of Minas Gerais. This re-emergence is related to the outbreak in 2016 and is currently ongoing in the southern region. Such events have increased the complexity of the epidemiological scenario in the country and the risk to public health. Although the urban cycle of yellow fever has not been recorded in Brazil since 1942, the recent outbreaks occurred close to areas heavily infested by potential vectors.

RNA Sequencing of YFV

Yellow fever is currently endemic in the tropical regions of Africa and South America. Despite the high fatality rate of yellow fever in Brazil, the experts' understanding of the disease is restrained by the limited viral genomic data.

To better understand the routes of YFV dispersion, the researchers tracked the spread and re-emergence of the virus throughout the country. This was made possible by analyzing metadata on human infections and 147 new genome sequences obtained from nonhuman primates. Some sequences were also taken from human patients within Brazil's Midwestern, Southern, Northern, and Southeastern regions.

The research team used a suitability index based on Aedes aegypti to capture the seasonality of reported human infections. Using spatial modeling, it was found that spatial hotspots with past reporting and low vaccination coverage coincided with the largest urban centers in the Southeastern region.

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