Yellow Fever Research and Response Collaborative Group

Late-Relapsing Hepatitis after Yellow Fever

Dr. Rezende and colleagues explored the occurrence of late relapsing hepatitis in individuals who had recovered from yellow fever during the 2016-2018 outbreak in Brazil. The findings revealed that some patients experienced a resurgence of liver dysfunction several weeks after their initial recovery, manifesting as elevated liver enzymes and bilirubin levels. The study suggests that this delayed hepatitis may be associated with the persistent presence of the virus or immune-mediated liver damage. This study highlights the importance of continuous monitoring of liver function in patients recovering from yellow fever and emphasizes the need for healthcare professionals to educate patients about the potential for late complications.

Characterization and Investigation of Risk Factors for Late-Relapsing Hepatitis After Yellow Fever

In this study, Dr. Rezende and colleagues have characterized the clinical course of the recently described late-relapsing hepatitis after yellow fever. Using data from a representative cohort of patients who had been diagnosed with yellow fever in Brazil and followed up at 30, 45, and 60 days post–symptom onset, they observed that some patients exhibited a rebound of aminotransferases, alkaline phosphatase, and total bilirubin levels, as well as jaundice, fatigue, headache, and low platelet levels, around 46–60 days after symptom onset. These findings have provided new data on the clinical course of late-relapsing hepatitis during the convalescent phase of yellow fever and highlighted the need for extended patient follow-up after acute yellow fever.

Yellow fever virus infection in human hepatocyte cells triggers an imbalance in redox homeostasis with increased reactive oxygen species production, oxidative stress, and decreased antioxidant enzymes

In this study, Dr Coelho Ferraz and colleagues have investigated how yellow fever virus affects human liver cells, focusing on oxidative stress mechanisms. They found that yellow fever infection increased reactive oxygen species levels and caused oxidative damage to lipids, proteins, and DNA. This was accompanied by a decrease in the activity of key antioxidant enzymes, indicating a shift toward a pro-oxidant environment. The findings suggest that oxidative stress plays a significant role in YFV-induced liver pathology, highlighting antioxidant biopharmaceuticals as potential therapeutic targets for yellow fever.

Serum soluble mediators as prognostic biomarkers for morbidity, disease outcome, and late-relapsing hepatitis in yellow fever patients

In this study, Dr. Fradico and colleagues have investigated how the immune response of patients with yellow fever develops during both the acute and convalescent phases. They identified that there’s a storm of mediators from the immune response (known as chemokines, cytokines, and growth factors) in the acute phase of the disease, especially in patients with worse outcomes. They also observed a difference in the immune response between patients who did or did not develop late-relapsing hepatitis. These findings provide crucial insights into how the immune response can influence yellow fever pathogenesis, progression, and the development of more severe or long-lasting illness.

Evaluation of humoral immune response after yellow fever infection: an observational study on patients from the 2017-2018 sylvatic outbreak in Brazil

In this study, Dr. Gonçalves and colleagues evaluated the humoral immune response developed against the yellow fever virus by comparing the levels of neutralizing antibodies in patients with the disease with those in healthy individuals vaccinated with the same virus. They found that patients who had recovered from yellow fever had produced more neutralizing antibodies than vaccinated individuals. This suggests that the immune responses triggered by the wild-type and vaccine viruses are different, likely due to mutations between the two viruses. The findings from this study highlight the importance of updating how we assess immune responses in people infected with yellow fever and stress the need for better monitoring in areas where the virus is common. Understanding these immune responses is vital for public health efforts, emphasizing the need for further research on yellow fever.

Yellow Fever Molecular Diagnosis Using Urine Specimens during Acute and Convalescent Phases of the Disease

In this study, Dr Rezende and colleagues evaluated the use of urine specimens for molecular diagnosis of yellow fever during both the acute and convalescent phases of the disease. Using samples from a large cohort of naturally infected yellow fever patients from recent outbreaks in Brazil, they have found that urine, in addition to serum, can be used to detect yellow fever virus RNA, offering a valuable alternative for diagnosis, particularly when serum is difficult to obtain. By analyzing data from patients in various stages of yellow fever, they demonstrated that urine remains a reliable diagnostic sample even after the acute phase. With a possible prolonged period of detection beyond the viremic phase, using urine samples coupled with serological tests, epidemiologic inquiry, and clinical assessment could provide a longer diagnostic window for laboratory yellow fever diagnosis.

Wild-type Yellow fever virus in cerebrospinal fluid from fatal cases in Brazil, 2018

In this study, Dr Rezende and colleagues have investigated the presence of wild-type yellow fever virus in cerebrospinal fluid from fatal cases during the 2018 outbreak in Brazil. Using samples from patients with severe neurological symptoms, they identified the presence of specific anti-yellow fever IgM, neutralizing antibodies, and yellow fever virus genomic RNA in the central nervous system, indicating neuroinvasiveness. By analyzing data from these fatal cases, the team demonstrated that yellow fever could cause severe neurological complications through viral invasion of the central nervous system, underscoring the need for improved clinical management and better understanding of severe outcomes during yellow fever outbreaks, as well as the role of yellow fever virus neuroinvasion and possible impacts in disease pathogenesis.