Risk of Death From Yellow Fever may be Detected Earlier

SÃO PAULO, BRAZIL – A study developed by the University of São Paulo (USP) and the Emílio Ribas Institute has uncovered four factors that point to the risk of death in patients with yellow fever.

Advanced age, elevated neutrophils (blood cells that are part of the innate immune system), increased AST liver enzyme, and increased viral load are the markers that point to the risk of a severe disease progression. The study emphasizes that out of every hundred people who are stung by mosquitoes infected with the yellow fever virus, ten percent will develop symptoms of the disease, and thirty percent may die.

“What most baffled us was that most patients came in well, complaining only of discomfort, body pain, and fever, and days later, some of them would die. It’s a very fast-evolving disease. It was a challenge to determine, upon the patients’ admission, which ones would progress poorly and which would have a favorable outcome. This was what we addressed in this study,” explained Esper Georges Kallás, professor at the Department of Infectious and Parasitic Diseases of the USP School of Medicine.

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

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

According to the State Secretariat of Health, in 2019, through June 3rd, 66 native cases of jungle yellow fever were recorded in the state and 12 of them resulted in death.

In 2018, 504 native cases were confirmed in several regions of the state, of which 176 resulted in death. There were also 261 animal diseases (death or illness of non-human primates).

Between January 11 and May 10, 2018, there were 118 patients suspected of having yellow fever admitted to the Hospital das Clínicas and another 113 to Emílio Ribas.

Diagnosis

After confirming the diagnosis, the study focused on 76 patients (68 men and eight women). Of the 76 patients, 27 (36 percent) died within 60 days of hospital admission.

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

The researchers also found that the yellowish color on the patients’ skin, a known characteristic of the disease, is not an indicator of its severity upon the patient’s admission to hospital.

“The yellowish coloration, which results from the destruction of liver cells by the virus, only occurs in cases of advanced deterioration. In our study, none of the patients who died reached the hospital displaying a yellowish skin coloration,” said Kallás.

To identify three of the indicators, excluding age, laboratorial tests are required. According to the professor, tests measuring the amount of neutrophils and the increase in liver enzyme are simple and produce results in up to one hour.

“The viral load of the yellow fever virus, which is an experimental test, is the most difficult one. It was developed for this study and is not well known. It is not commonly available in clinical testing laboratories,” he explained. He believes that the availability of this test would help not only to identify the indicator, but also the diagnosis itself.

In cases of new yellow fever outbreaks, the results found in the study now allow physicians to screen patients at the time of admission to health services, pinpointing those that may potentially evolve into more severe cases. Thus, it is now feasible to anticipate admissions to intensive care units, increasing the chances of survival.

Critical mass

“We are building a critical mass of information that will help physicians when assessing patients, initially who is doing better, who is doing worse and optimize the availability of resources in the hospital. Evidently, it helps to improve the health care of these people,” said the researcher.

Another consequence of the findings is the suggestion that antiviral drugs may help in the treatment of yellow fever. “For the first time the correlation of the viral load with the worsening of the disease is reported,” said Kallás.

According to the investigator, other projects are evaluating drugs that could be used in this case.

“If a patient with yellow fever comes in at the very beginning, could the antiviral drug we administer cut off the virus’ multiplication and improve the patient’s prognosis? Since the viral load is a factor, this has the potential to change the history of yellow fever survival if we find a medicine that is effective,” he said.