From the Guidelines
Yellow fever diagnosis is most accurately made through blood tests, specifically viral culture, identification of yellow fever virus antigen or nucleic acid, or detection of yellow fever-specific immunoglobulin M (IgM) antibody by capture ELISA 1.
Diagnosis Methods
The diagnosis of yellow fever can be achieved through various methods, including:
- Viral culture of blood or tissue specimens
- Identification of yellow fever virus antigen or nucleic acid in tissues using immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA) antigen capture, or polymerase chain reaction tests
- Detection of yellow fever-specific immunoglobulin M (IgM) antibody by capture ELISA with confirmation of >4-fold rise in neutralizing antibody titers between acute- and convalescent-phase serum samples
Importance of Early Diagnosis
Early diagnosis is crucial for proper patient management and implementing public health measures to prevent disease spread, as no specific antiviral treatment exists for yellow fever 1.
Laboratory Testing
These tests must be performed in specialized laboratories with appropriate biosafety measures.
Clinical Presentation
The clinical spectrum of yellow fever ranges from subclinical infection to overwhelming pansystemic disease, with symptoms including fever, prostration, headache, photophobia, lumbosacral pain, extremity pain, epigastric pain, anorexia, and vomiting 1.
Public Health Implications
Healthcare providers should collect blood samples as early as possible in the illness and may need follow-up samples 2-3 weeks later for complete diagnosis, to prevent disease spread and implement public health measures 1.
From the Research
Yellow Fever Diagnosis via Blood Tests
- Yellow fever (YF) virus can be diagnosed through various blood tests, including the plaque reduction neutralization test (PRNT) 2, which is considered the most specific serological test for differentiating flavivirus infections.
- The PRNT has shown good robustness and high precision, specificity, and lower limit of quantification (LLOQ) 2, making it suitable for use in YF diagnostic and vaccine clinical trials.
- Other diagnostic methods include quantitative real-time PCR (qPCR) 3, 4, which can detect YF virus-specific nucleic acids, and enzyme-linked immunosorbent assay (ELISA) 5, which can detect YF antigen in serum.
- qPCR has been shown to be a faster and more sensitive method for detecting YFV RNA in serum and urine samples 4, 6, and can be used for diagnosis, vaccine production, and quality control.
- The detection of YFV RNA in urine samples has also been reported, with a possible prolonged period of detection beyond the viremic phase 6, which could provide a longer diagnostic window for laboratory YF diagnosis.
Diagnostic Methods
- Plaque reduction neutralization test (PRNT): considered the most specific serological test for differentiating flavivirus infections 2
- Quantitative real-time PCR (qPCR): can detect YF virus-specific nucleic acids in serum and urine samples 3, 4, 6
- Enzyme-linked immunosorbent assay (ELISA): can detect YF antigen in serum 5