Laboratory diagnosis of yellow fever virus infection

Overview

Biosafety considerations

All biological samples (whole blood, serum or fresh tissue) should be considered as potentially infectious (8). All laboratory personnel handling these samples must be vaccinated against yellow fever and use appropriate personal protective equipment. Furthermore, it is recommended to carry out all procedures in certified class II biosafety cabinets and to take all necessary precautions to avoid percutaneous exposure. Procedures for handling non-human primate samples should be carefully assessed according to national regulations and the biosafety manual of each laboratory, and the use of class III biosafety cabinets should be considered.

Virological diagnosis

• Molecular diagnostics: Viral RNA can be detected in serum samples during the first 10 days since the onset of symptoms (viremic phase) or even longer than 10 days in severe cases, by molecular methods such as conventional (end-point) or real-time reverse transcription polymerase chain reaction (RT-PCR) (Figure 1). A positive result by molecular testing (when using the appropriate controls and interpretation) confirms the diagnosis of YFV infection. 
• Viral isolation: Viral isolation can be performed through intracerebral inoculation in mice or in cell culture (using Vero or C6/36 cells; may be performed under BSL2 containment). Because of its complexity, this methodology is rarely used as a first-line diagnostic tool. Yellow fever: Detection and laboratory diagnosis 2 However. virus isolation capacity is important for the characterization of circulating strains, to produce diagnostic reagents and for research studies.
•  Immunohistochemistry: Histopathological analysis with immunohistochemistry performed on liver sections (and other tissues) is considered the "gold standard" assay for the diagnosis of yellow fever in fatal cases. Additionally, molecular detection can also be performed in fresh or formalin fixed (paraffin-embedded) tissue samples to confirm fatal cases.