On April 30 this year, a 44-year-old man from São João da Boa Vista, a town 210 kilometers north of the São Paulo state capital, died of yellow fever. It was the second fatality from the disease in 2023 in the state, where for three years previously there had been no recorded human cases. After the most intensive phase of the current outbreak — the biggest in decades, which between 2016 and 2020 afflicted some 2,300 people and killed more than 600 in the Brazilian Southeast, Midwest and South — yellow fever began to relent. Its incidence fell sharply, but circulation of the virus that causes it continued. According to data from the Pan American Health Organization (PAHO), between July 2022 and mid-March 2023 there were 300 suspected cases in Brazil, of which three were confirmed, with one death; the second fatality in São Paulo occurred subsequently. During the same period, hundreds of monkeys were found dead in forests close to urban regions, suspected of having been infected with the virus, which can cause lesions in the liver, kidneys, and heart, killing up to half of the people contracting the serious form of the disease.
“This is the first time there has been such a long-lasting outbreak outside Amazonia: almost 7 years of active transmission, at some stages with two varieties of the virus circulating simultaneously,” explains virologist Camila Zanluca, a researcher at the Carlos Chagas Institute, a unit of the Oswaldo Cruz Foundation in Paraná State (ICC/FIOCRUZ-PR). Zanluca and Italian virologist Marta Giovanetti, from FIOCRUZ in Rio de Janeiro, are the lead authors of an article published in the journal Science Advances in September, describing the dynamics around the recent spread of the virus in the country. Researchers from 46 Brazilian and overseas institutions sequenced the genome of 147 samples of the virus obtained from humans, monkeys, and mosquitoes infected between 2015 and 2022, and compared these with 296 other genomes from specimens of the pathogen that circulated in recent decades in Central and South American countries — yellow fever is endemic in 13 countries across the region and in a further 34 on the African continent.
Analysis of such a large number of virus genomes — the biggest ever conducted on Brazilian samples — provided some unexpected findings. The first is that in this current outbreak, the yellow fever agent arrived in southcentral Brazil two or three years before originally thought, from somewhere in Amazonia. “Current data indicate that the virus arrived in southeastern Brazil between the end of 2013 and the beginning of 2014,” reports virologist Luiz Carlos Júnior Alcântara, a researcher at the Rene Rachou Institute in Minas Gerais State, also a unit of FIOCRUZ, and a coordinator of the current study. Alcântara collaborated on previous research, published in 2018 in the journal Science, which, based on analysis of 62 genomes, had calculated that the virus was believed to have reached the region, more specifically the state of Minas Gerais, only at the end of 2016.
The second piece of news in the Science Advances article is that in the last seven years, three variants of the virus circulated in southcentral Brazil, two of which concurrently at certain times. Given the technical name Clados Ia, IIb, and IIIc, all are part of the South American I genotype, the most common in the country. However, they differ due to individual alterations, particularly in the gene that codes an enzyme which assists in the replication of the virus’s genetic material within the host cells (mosquito, monkey, or human).
By combining the genetic characteristics of the samples with the location from which they were collected, the researchers were able to partially reconstruct the pathways taken by each variant of the virus. From northern Brazil, members of Clado Ia entered the Southeast via Minas Gerais around the beginning of 2014, although the first cases in monkeys and humans were only detected at the end of 2016. From there they moved on to Espírito Santo State, and then spread to the states of Rio de Janeiro and Bahia, the latter in the Northeast, as indicated in an article published in 2019 in the Journal of Virology, from a study also coordinated by Alcântara.
