The virus had changed enough that the tests no longer caught it.
Sabiá virus has caused 4 deaths since 1990 in São Paulo, but genetic mutations made it undetectable by existing tests until researchers developed improved diagnostic primers. The virus shows 89% genetic identity to 1990 reference strains, with mutations in key diagnostic target regions, suggesting decades of silent circulation and possible undetected cases.
- Four confirmed deaths from sabiá virus since 1990 in São Paulo state
- Two additional fatal cases identified in 2019-2020 through metagenomics
- Virus shows 89% genetic identity to 1990 reference strain; mutations in diagnostic target regions
- Virus has been circulating in Brazil for 142 years based on phylogenetic analysis
- Brazil's first biosafety-4 laboratory (Orion) scheduled to open in 2030 in Campinas
Brazilian researchers developed a new diagnostic method for sabiá virus, identifying genetic mutations that prevented detection in two fatal cases from 2019-2020. The virus has been circulating for 142 years with significant genetic variation.
A virus has been moving through Brazil for nearly a century and a half, leaving bodies in its wake, and we have only just begun to see it clearly. In 2019 and 2020, two men died in São Paulo state from a syndrome that looked like yellow fever but wasn't—acute hemorrhagic illness coupled with neurological collapse. Their blood samples tested negative for everything the hospitals knew to test for. It wasn't until researchers at a joint Brazil-UK research center applied a newer technique, one that doesn't require you to know what you're looking for in advance, that the culprit emerged: sabiá virus, a pathogen so rare and so poorly understood that it had slipped past the diagnostic net.
The virus itself is not new. It was first identified in 1990 in a case near Cotia, in the interior of São Paulo. A second confirmed case came in 1999. Since then, four deaths have been recorded in the state—a thin trail of mortality that suggests either extreme rarity or, more likely, a pattern of silent circulation punctuated by occasional, catastrophic human contact. The researchers who made this discovery, led by Ingra Morales Claro at the University of São Paulo's School of Medicine, found something troubling in the genetic material they recovered: the virus had changed. Significantly. Over the three decades since that first documented case, sabiá had accumulated mutations—enough that the diagnostic tests built around the 1990 reference strain no longer reliably caught it. The new genomes showed only 89 percent genetic identity to the original, with alterations concentrated precisely in the regions where laboratory tests were designed to detect the virus. This was not a failure of the old tests. It was evidence of evolution in real time.
The two fatal cases that revealed this pattern told a story of rural exposure and delayed recognition. The first victim was a 63-year-old agricultural worker from Assis who came to São Paulo's Hospital das Clínicas on December 10, 2019, and died two days later. The second was a 52-year-old from Sorocaba with a history of walking through forested areas. He sought care at a basic health unit on December 30, 2019, was transferred to the same hospital with suspected yellow fever, and died on January 11, 2020. Both tested negative for yellow fever. Both tested negative for sabiá using the standard methods. It was only when researchers applied metagenomics—a technique that sequences everything in a blood sample and lets you identify pathogens after the fact, rather than before—that the virus revealed itself. Once they knew what they were looking for, they went back through records of seven other cases of acute hemorrhagic and neurological syndrome that had tested negative for yellow fever. One of those cases, from 2019, was the Assis worker.
The research team, part of the CADDE center (Centro Conjunto Brasil-Reino Unido para Descoberta, Diagnóstico, Genômica e Epidemiologia de Arbovírus), responded by developing new diagnostic primers—small DNA fragments designed to detect the mutated virus in laboratory tests. Claro explained the logic plainly: more than thirty years had passed since the reference strain was isolated. Of course the virus had changed. The old tests were built on outdated genetic blueprints. The new primers, designed to account for the mutations that had accumulated, were sent to the Adolpho Lutz Institute in São Paulo, the state's reference laboratory for this kind of work. They offer a more precise way to catch the virus in future cases—if there are future cases.
What remains unknown is where the virus lives when it is not infecting humans. Researchers suspect wild rodents serve as the reservoir, but this has not been confirmed. All documented cases have occurred in rural areas where humans and animals might interact. The silence between cases—years or decades passing with no confirmed infections—suggests either that transmission is genuinely rare or that cases are occurring and going unrecognized, their deaths attributed to other causes. Ester Sabino, who leads the Brazilian side of the CADDE center and who sequenced the first SARS-CoV-2 case in Brazil in 2020, warned that there were likely other cases in the past that were never identified. The virus has been circulating for 142 years, according to phylogenetic analysis. Four confirmed deaths in thirty years is almost certainly an undercount.
The sabiá virus presents another problem: it is considered one of the highest-risk pathogens for laboratory transmission by aerosol, which means it requires the maximum level of biosafety containment to study safely. South America has no such facility. The reference strain is currently stored in the United States. Brazil is building one. The Orion laboratory, under construction at the National Center for Research in Energy and Materials in Campinas, is scheduled to open in 2030. Until then, the virus remains partly out of reach—knowable through genetic sequences and blood samples, but not safely manipulable in the region where it circulates. The new diagnostic method is a step forward, a way to see what was invisible. But the deeper work of understanding how this virus survives, where it hides, and how to prevent the next death will have to wait.
Citações Notáveis
Probably there were other cases in the past that were not identified. It is important to know the virus, develop the tests, and study the changes that occur in its genome in order to anticipate future new cases and even outbreaks of the disease.— Ester Sabino, School of Medicine, University of São Paulo
When we analyzed the genome of the new cases, we identified mutations in the target regions of the primers that prevented detection by existing diagnostic tests. We modified these regions and now it is possible to identify the circulating strains.— Ingra Morales Claro, researcher who developed the diagnostic method
A Conversa do Hearth Outra perspectiva sobre a história
Why did these two deaths in 2019 and 2020 go unrecognized for so long?
The virus had mutated enough that the diagnostic tests—which were built around a 1990 reference strain—couldn't find it. The tests were looking for a genetic signature that no longer existed in the circulating virus.
So the virus was there all along, but invisible to the tools we had.
Exactly. And that raises a darker question: how many other cases have there been that we never caught? The virus has been in Brazil for 142 years. We have four confirmed deaths. That's probably not the whole picture.
What changed in the virus's genetics?
The mutations appeared in the exact regions where the diagnostic tests were designed to bind and detect it. It's almost like the virus evolved around our ability to see it.
Is this virus spreading more, or are we just noticing it now?
We don't know. The cases are so rare and so far apart that it's hard to say. But the fact that we found two cases in two years after decades of silence suggests we might be looking more carefully now—or something about the virus or its transmission is changing.
Where does it come from?
That's the unsolved part. We think wild rodents are the reservoir, but we haven't proven it. Both fatal cases were in rural areas where humans and animals interact. Beyond that, it's still a mystery.
And we can't study it safely here yet.
Not at the highest level of containment. The virus is too dangerous for aerosol transmission. The reference strain is in the United States. Brazil's first biosafety-4 lab opens in 2030. Until then, we're working with sequences and blood samples, not the living virus.