Genomic surveillance of the yellow fever outbreak in São Paulo


The yellow fever virus is usually restricted to the Amazon region, but the virus circulated in southeastern Brazil between 2016 and 2018, causing the worst epidemic and epizootic outbreaks in decades. The Ministry of Health confirmed 2,251 cases of yellow fever in humans and 1,567 cases in monkeys in Brazil between December 2016 and June 2019.

According to a study published in the journal PLOS Pathogens, the three epidemic / epizootic waves that occurred during this time in the state of São Paulo, the most populous in the southeast, were caused by different lineages of the virus. In the first wave (July 2016 – January 2017), the virus entered the state from the north, likely from the neighboring state of Minas Gerais, and spread mainly in cities such as São José do Rio Preto and Ribeirão Preto. The second wave (February-June 2017) was more intense and flooded the area from the border with Minas Gerais on Poços de Caldas to Campinas.

Most of the cases were reported in the third wave (July 2017 – February 2018). After reaching São Paulo City, the virus spread south to the Ribeira Valley, where it found densely populated cities with low vaccination rates and became a major public health problem.

These results, published in the journal by an international research group supported by FAPESP, were based on genomic analysis of 51 virus isolates extracted from both mosquitoes in the affected areas and from monkeys that had died of the disease. The material was sent by the Center for Epidemiological Surveillance (CVE) – an agency of the São Paulo Ministry of Health – to the Adolfo Lutz Institute (IAL), the central public health laboratory in São Paulo.

Based on the geographical and temporal distribution of cases in non-human primates on phylogenetic analysis [studying the mutations in the viral genome that lead to the emergence of novel lineages] and for phylogeographic analysis [studying the processes that determined the geographical distribution of the different lineages]It was possible to determine when the virus reached the state of São Paulo, how quickly and how it spread and what facets it had. “

Renato de Souza, researcher at IAL and one of the main authors of the article

This level of detail when describing an epidemic is only possible thanks to the use of MinION’s genetic sequencing technology, Souza explained. The platform is portable, fast, and inexpensive, and enables real-time monitoring of cases where they occur.

The strategy was first used in 2016 in Brazil to track the movement of the Zika virus in America (read more at More recently, it has helped researchers at the Brazilian-UK Center for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology (CADDE) track the progress of COVID-19 in Brazil. The project is led by Ester Sabino, a researcher at the University of São Paulo, and Nuno Faria from Oxford University in the UK and supported by FAPESP (, the UK Medical Research Council and the Newton Fund.

Accidental host

The yellow fever virus is permanently circulating in the Amazon, occasionally meeting favorable conditions for it to escape. To do this, a population of the vector mosquito must come into contact with a population of wild primates that is dense enough to maintain the transmission chain for some time.

“This extension is not permanent,” he said. “The virus eventually loses the ability to circulate in the environment and only returns when reintroduced. Between 2016 and 2018, the range expanded at an unprecedented rate. The conditions for the virus to spread were just right It infected wild primates in Serra da Mantiqueira [forest area of the state of São Paulo] and reached an area near the large zoological park on the outskirts of São Paulo. This can happen again in a few years if the primate populations in these locations grow sufficiently. “

Epidemiologically, there was an outbreak of Sylvatic yellow fever during this period, Souza said. Although there have been many cases in humans, transmission has only occurred outside of the urban setting via tree mosquitoes such as Haemagogus and Sabethes.

“In this case, human exposure was accidental. Increased human intrusion into natural environments and forests was one of the factors,” he said, adding that the incidence of the disease would have been had an urban chain of transmission through Aedes aegypti been established was far larger and reached the level of dengue outbreaks.

“The problem is that the Sylvatic transmission structure is getting closer and closer to urban areas, which increases the risk of the virus being introduced into the urban context,” he said.

Tracking the spread of the pathogen in monkey populations was seen as an effective epidemiological surveillance strategy, as it facilitates the early detection of risk areas and the planning of control strategies such as vaccination campaigns.

“A surveillance strategy based solely on monitoring cases in humans only detects 20% of those infected, which is the proportion of symptoms, so underreporting is always significant. In monkeys, there are species where 90% develop symptoms and Monitoring these animals will identify the disease when the virus begins to spread and in time to implement combat programs, “Souza said.


São Paulo State Research Support Foundation

Journal reference:

Hill, SC, et al. (2020) Genomic surveillance of animal diseases with yellow fever viruses in São Paulo, Brazil, 2016 – 2018. PLOS pathogens.

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