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Wednesday, June 12, 2019

Study identifies predictors of mortality in patients with yellow fever - Lancet 2019

Researchers identified numerous clinical and laboratory predictors of mortality in patients with yellow fever, including higher RNA plasma viral load, according to findings reported in The Lancet Infectious Diseases.
“Although only 10% to 50% of patients infected with yellow fever virus develop symptoms, yellow fever virus infection is recognized as a very severe disease, with associated mortality as high as 50% in symptomatic patients,” Esper G. Kallas, MD, PhD, from the Clinical Hospital at the University of São Paolo, and colleagues wrote.
Kallas and colleagues’ observational cohort study included adult patients aged 18 years or older with yellow fever who were admitted to the hospital between Jan. 11, 2018, and May 10, 2018. The final analysis included 76 patients with yellow fever virus, confirmed either through detectable yellow fever virus RNA in blood or at autopsy.
The researchers reported that 36% of patients died within 60 days after hospital admission. According to the findings, risk factors associated with higher mortality included older age; male sex; higher leukocyte and neutrophil counts; higher alanine aminotransferase, aspartate transaminase, bilirubin and creatinine; prolonged prothrombin time; and higher yellow fever virus RNA plasma viral load.
Of the 11 patients with neutrophil counts of 4,000 cells/mL or greater and viral loads of 5.1 log10 copies/mL or greater, 100% died compared with 11% of the 27 patients with neutrophil counts of less than 4,000 cells/mL and viral loads of less than 5.1 log10 copies/mL, the researchers reported.
“Our findings have several implications for the care of patients with yellow fever virus,” Kallas and colleagues wrote. “Identification of poor outcome markers could help guide resource allocation and strategies to provide intensive care for patients with potentially severe disease, supporting a rational approach during disease outbreaks. Medical services and intensive care units can be overwhelmed during the peak of epidemics and decision-making referral algorithms might take advantage of simple clinical and laboratory evaluation.”
In a related editorial, Annelies Wilder-Smith, MD, PhD, DTM&H, MIH, professor of emerging infectious diseases at the London School of Hygiene & Tropical Medicine, and colleagues explained that some of the study findings from Kallas and colleagues are “as expected.”
“Older age is also associated with more severe outcomes in other flavivirus infections, including Japanese encephalitis and West Nile encephalitis,” they wrote. “However, a potential novel finding is the higher viral load associated with fatal outcomes, suggesting a possible causative role, as has been shown in a hamster model. This finding has implications for improving understanding of the pathogenesis of severe disease and the potential role of early antiviral treatment in mitigating severity.”

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