Yellow fever virus (YFV) is widely distributed in the tropics of South America and Africa, being responsible for massive yellow fever outbreaks causing deaths of thousands of people in recent years. Recently, in December 2016, a huge sylvatic YFV outbreak took place in Southeast Brazil, causing 2,155 cases with approximately 46% of total cases (n=1,002) and 37% of deaths (n=340) taking place in Minas Geraisstate. YFV usually occurs in remote areas of Africa and the Americas where patients have little or even no access to advanced medical care and laboratory tests. In that way, much of what we know about YFV in humans is very limited. The same is valid for pathogenesis, viral and immunological markers during the disease course, markers of prognosis, and treatment approaches, the convalescence phase and the characterization of the lineages causing the last outbreaks in Brazil. The recent YFV outbreaks in Southeast Brazil create an unprecedented opportunity to analyze data and well-preserved samples from hundreds of hospitalized YFV patients. Our unique well-characterized cohorts include: (i) patients who evolved to death; (ii) patients who recovered; (iii) patients who recovered and presented a clinical syndrome was named late hepatitis-like syndrome after yellow fever (LHep-YF); and (iv) patients who received therapeutic intervention as an off-label treatment with sofosbuvir. Here we propose to (i) redefine the clinical course of yellow fever and determine the social, demographic, and co-morbid risk factors for severe presentations of disease, including development of LHep-YF, (ii) investigate the viral and immunologic pathogenesis of YFV throughout the continuum of disease and (iii) identify virological and immunological biomarkers of YFV prognosis, including LH ep-YF occurrence and impacts of potential treatments. The interdisciplinary approach integrating basic and applied virology, immunology, epidemiology, and clinical infectious disease and a group of experienced researchers guarantees the development of the proposal, filling important gaps on epidemiology, clinical disease, pathophysiology, and biology of YFV. This information will be crucial for the establishment of protocols and more applied studies to prevent morbidity and mortality from this pathogen.
Funding provided by NIH, R01: A. Desiree LaBeaud Co-PI with Olindo Filho, PhD (12/2019 – 11/2023)