Detection of yellow fever virus genome in urine following natural infection or vaccination: review of current knowledge 1985-2023.

Background: Yellow fever virus (YFV) is endemic in the (sub)tropical regions of Africa and South America and is prone to cause epidemics. Molecular testing of YFV by reverse transcription-polymerase chain reaction (RT-PCR) was recently adopted by WHO using blood. Urine is a non-invasive diagnostic specimen which has been proven to be useful in diagnosing several flavivirus infections. Until now, systematic data on the usefulness of urine in YFV molecular diagnostics was lacking.

Methods: We have carried out an extensive literature search using key words "yellow fever AND urine" in PubMed/Medline, Embase and Web of Science.

Results: The search resulted initially in 113 publications. All titles and abstracts were screened and 15 were analyzed in detail. After natural infection (10 articles), the detection ratio of YFV in blood with RT-PCR was 61 % (105/171 samples) vs. 59 % (139/234) in urine from patients with mild/severe infections. YFV could be first detected at average 4.3 days in blood vs. 6.1 days in urine and last detected till 17.2 vs. 31.1 days respectively (significant difference p < 0.05). Viral load over time in blood was not statistically different from urine. Virus could be isolated from blood, urine and semen. Following vaccination, virus was detected longer in patients with vaccine adverse events (VAE) compared to healthy vaccinees (average 34 vs. 25 days, not significant p > 0.05).

Conclusion: YFV can be detected in urine later but longer. Thus, we see added value for YF molecular diagnostics and sequencing and recommend it besides blood as a standard specimen, especially for late samples post onset.