Foto: Marcelo Camargo/Agência Brasil

With information from Camila Maciel, Agência Brasil

Research developed by the University of São Paulo (USP) and Emílio Ribas Institute identified four factors that indicate risk of death in patients with yellow fever. Older age, elevated neutrophil counts (blood cells that are part of the innate immune system), increased liver enzyme AST, and higher viral load are the markers that indicate the risk of a severe disease course. Of the 100 people who are bitten by mosquitoes infected with the yellow fever virus, 10% will develop symptoms of the disease, and 30% may die.

“What puzzled us the most was that most patients arrived well, only complaining of discomfort, body aches, and fever, and days later some of them died. It is a very rapidly evolving disease. It was a challenge to determine, at the patient’s entrance, which one would evolve very badly from the disease and which would have the most favorable course. That is what we approached in this work, ”explained Esper Georges Kallás, a professor at the Department of Infectious and Parasitic Diseases at USP’s School of Medicine.

Another 19 researchers, supported by the São Paulo State Research Support Foundation (Fapesp), subscribe to the study, published in the scientific journal Lancet.

Kallás points out that samples for analysis were collected from patients during the yellow fever outbreak in Sao Paulo last year.

According to the State Department of Health, in 2019, until June 3, 66 autochthonous cases of wild yellow fever were recorded in the state and 12 of them evolved to death.

In 2018, 504 autochthonous cases were confirmed in various regions of the state, of which 176 resulted in death. There were also 261 epizootic diseases (death or illness of nonhuman primates).

Between January 11 and May 10, 2018, 118 patients with suspected yellow fever were admitted to Hospital das Clínicas and 113 to Emílio Ribas.


After confirmation of the diagnosis, the study focused on 76 patients (68 men and 8 women). Of the 76 patients, 27 (36%) died within 60 days of hospitalization.

Eleven patients with a neutrophil count of 4,000 cells / ml or greater and a viral load of 5.1 log10 copies / ml (or approximately 125,000 copies of the virus per milliliter of blood) died, compared with three deaths among 27 patients with neutrophil counts less than 4,000 cells / ml and viral loads of less than 5.1 log10 copies / ml (less than 125,000 copies / ml).

The researchers also found that the yellowish coloration on the patients’ skin, a known feature of the disease, is not a marker of severity at the time of patient entry into the hospital.

“Yellowish coloration, due to the destruction of the liver cells by the virus, only appears in cases of advanced worsening. In our study, none of the patients who died arrived at the hospital with a yellow color, ”said Kallás.

To identify three of the markers, excluding age, laboratory tests are required. According to the professor, what measures the amount of neutrophils and the increase in liver enzyme are simple tests with a maximum of one hour.

“The most difficult is the viral load of the yellow fever virus which is an experimental trial. It was developed for this study, and is not popularized. It is not usually available in clinical analysis laboratories, ”he explained. He evaluates that the availability of the exam would assist not only in marker identification but also in the diagnosis itself.

In cases of new outbreaks of yellow fever, the results found in the study now allow physicians to screen patients at the time of entry into health services, identifying those who may potentially progress to more severe cases. Thus, it is possible to anticipate hospitalizations in intensive care units, increasing the chances of survival.

Critical mass

“We are creating a critical mass of information that will help the doctor when evaluating the patient, initially who is doing better, who is doing worse and optimizing the availability of resources in the hospital. Evident that helps to improve the health care of these people, ”said the researcher.

Another consequence of the finding is the hypothesis that antiviral drugs may aid in the treatment of yellow fever.

“For the first time, the association between the amount of virus [viral load] and worse disease is described,” said Kallás.

According to the researcher, other projects already evaluate medications that could be used in this case.

“If a yellow fever patient arrives early on, does giving us an antiviral drug not cut the virus’s multiplication and improve that person’s prognosis? Since the amount of virus is a factor, it has the potential to change the history of survival in yellow fever if we find a remedy that is effective, ”he said.