A new research carried out in co-participation by the Institute of Tropical Medicine (IMT) and Hospital das Clínicas (HC), both from the USP School of Medicine (FMUSP), which diagnosed two new cases of sabiá virus (SABV) infection in 2019, deepened the investigation of this causative agent of Brazilian hemorrhagic fever. Previously, only four infections of this type had been detected in the country, the last one more than 20 years ago. The two diagnoses were made in the midst of an outbreak of yellow fever in the Southeast region of the country.
“We carried out this study during the yellow fever epidemic, so in cases where we were unable to make the diagnosis, we went after other viruses”, explains physician Ana Catharina Nastri, from the Division of Infectious Diseases at HC-FMUSP. “To our surprise, we found these two cases to be extremely rare.” According to her, advances in pathological anatomy, especially in electron microscopy, allowed for a more in-depth study of the Brazillian mammarenavirus, or sabiá virus, bringing new information about its clinical manifestations, histopathology and the possibility of hospital transmission. The findings were published in an article in the journal Travel Medicine and Infectious Disease, in May of this year, with Dr. Nastri as the first author and guidance from Professor Ana S. Levin, from the Department of Infectious and Parasitic Diseases at FMUSP.
The name of the pathogen is a reference to the Sabiá neighborhood, located in the municipality of Cotia, in Greater São Paulo, where the first victim is suspected to have been infected. Although there are several types of Mammarenavirus described in different South American countries, SABV is characteristic of Brazil. “Some of these viruses have the most well-known viral cycle, while our thrush virus has very little data”, says the doctor. “We still don’t know what its reservoir is in nature, how it is transmitted, and whether there would be infection through human-to-human contact.”
Prior to the study, only four SABV infections had been recorded. Apparently, one of them took place in the city of Cotia, in 1990, and another, in the city of Espírito Santo do Pinhal, in 1999, both located in the rural area of the State of São Paulo. In both cases, the contagion affected rural workers who died as a result of complications from hemorrhagic fever. The other two infections occurred in laboratory workers who were likely infected while handling the virus. Both survived.
“Case A and Case B”
The two new cases detected, called “Case A and Case B” in the study conducted at Hospital das Clínicas, occurred in the cities of Sorocaba and Assis (in the interior of São Paulo), respectively, and both patients were admitted to Hospital das Clínicas (HC) with a diagnostic hypothesis of a severe case of yellow fever. The first was a 52-year-old man who had walked through the forest in the city of Eldorado (170 kilometers south of São Paulo) and began to experience symptoms such as muscle pain, abdominal pain and dizziness. The next day, he developed conjunctivitis, being medicated at a local hospital and then released. Four days later, he was hospitalized again with a high fever and drowsiness. Yellow fever was suspected and he was transferred to Hospital das Clínicas.
During hospitalization, his clinical condition worsened until he was transferred to the Intensive Care Unit (ICU), ten days after the onset of symptoms, with significant bleeding, renal failure, reduced level of consciousness and hypotension, and he died two days later.
Case B refers to a 63-year-old man, a rural worker from Assis (440 kilometers west of São Paulo), who presented with fever, generalized myalgia, nausea and prostration. Symptoms worsened and eight days later he was admitted to the HC with depressed level of consciousness and respiratory failure requiring intubation. Severe left ventricular dysfunction (drastic reduction in the pumping function of part of the heart) led to refractory shock and eventual death 11 days after the onset of symptoms.
What do we know and what remains to be known
To carry out the diagnoses, the scientists used the metagenomic technique, which makes it possible to identify as-yet-unknown viruses through the extraction, replication and eventual sequencing of the genetic material of the infectious agent. This material is then compared to other organisms in bioinformatics databases, with information from pathogens from around the world. By relating the virus found in patients with other types of Mammarenavirus and verifying the compatibility of the discovery with clinical practice, it was determined that it was SABV.
In the analysis of the two fatal infections of the study, the researchers identified symptoms similar to those registered in the cases of the 90’s. “The clinical part is very similar to what we had seen before, and between the two new cases, the manifestation was also very similar”, says Ana Nastri. In all cases, there was a significant impairment of the liver and organs associated with the production of defense cells, which may have facilitated the emergence of secondary infections, making the initial diagnosis more complex.
As for the geography of infections, the four registered cases had as a common point infections that occurred in rural areas. “We inferred, based on the other Mammarenavirus in South America, that the person is probably contaminated by inhalation of viral particles, perhaps from rodent feces. But this is not proven precisely because we have very few cases described”, says Ana. The doctor also warns that, precisely because they are rural areas with fewer laboratory and diagnostic resources, some cases may have evaded clinical analysis, making it impossible to have a complete overview of Brazilian hemorrhagic fever. “We don’t know if there really aren’t any milder cases, like yellow fever, which ranges from the severe case to those who have no symptoms at all.”
An important difference of the study in relation to previous reports of the virus refers to the incidence of hospital transmission. Scientists at the IMT and Hospital das Clínicas did not find any such infections during contact tracing. “This shows that with the usual precautions, such as a mask, glove, glasses and apron, there was no transmission, and it makes us a little calmer about our virus”, says Ana Nastri. She points out, however, that it is not yet possible to draw a conclusion, as these are only two cases.