In October 2016, a male New York resident aged 74 years developed fever, myalgia, nausea, and vomiting while traveling in Peru, 3 days after visiting the northern Amazon area. During the next 2 days, he experienced fever, abdominal pain, and watery diarrhea and was admitted to a hospital in Peru, where Entamoeba histolytica was detected in his stool. He was treated with intravenous fluids and antibiotics and released 1 day after admission.

His condition worsened, however, and he returned to New York and immediately sought care at a hospital emergency department, where he was found to be afebrile, slightly confused, and jaundiced. Laboratory tests revealed leukopenia, thrombocytopenia, acute renal failure, liver dysfunction, and a metabolic acidosis. He was transferred from the emergency department to a tertiary care center, where he was admitted and received intravenous fluids, antibiotics, and hemodialysis.

During the next 2 days, he developed melena and disseminated intravascular coagulation. He experienced multiple episodes of ventricular fibrillation and died 3 days after admission. Autopsy revealed gastrointestinal hemorrhage and subtotal hepatocellular necrosis. Testing for selected viral, bacterial, and parasitic agents was negative, except for antibody to Salmonella H type A/B.

He had not received yellow fever vaccine before traveling. Serum specimens and tissues were sent to Wadsworth Center, the New York State Public Health Laboratory, and CDC to test for yellow fever virus and other pathogens.

A serum specimen collected 7 days after illness onset tested positive for flaviviral RNA by reverse transcription–polymerase chain reaction (RT-PCR), and the amplicon sequencing was consistent with yellow fever virus. A serum specimen obtained at autopsy was positive for yellow fever immunoglobulin M antibodies. Yellow fever RT-PCR assays performed on RNA extracted from formalin-fixed, paraffin-embedded liver tissue were positive; amplicon sequence analysis revealed highest identity with wild-type yellow fever virus strains.

An immunohistochemical assay for yellow fever virus performed on the liver tissue demonstrated staining of necrotic hepatocytes throughout the lobules, without mesenchymal staining. The morphologic features of fulminant active hepatitis and the immunohistochemical staining pattern and sequencing results, in combination with the patient’s travel history to a region of Peru where yellow fever is endemic, lack of yellow fever vaccination, and clinical history supported the diagnosis of infection with wild-type yellow fever virus.