Orthoflavivirus infections among patients with undiagnosed acute febrile illness admitted to fever hospitals, Greater Cairo, Egypt- A pilot study

Aim: This study aimed to investigate the role of Orthoflavivirus infections, in patients with undiagnosed acute febrile illness (AFI) admitted to fever hospitals in Greater Cairo using integrated molecular and serological techniques. Methods: An observational cross-sectional study was conducted over nine months in 2018 on 92 undiagnosed AFI patients admitted to Abbassia and Imbaba Fever Hospitals. Anti-West Nile virus (WNV) and anti-Dengue virus (DENV) IgM enzyme-linked immunosorbent assays were performed to detect recent infections. Reverse transcription polymerase chain reaction was used for panflavivirus RNA detection. Positive samples were analyzed for DENV-specific RNA. Results: Patients ranged in age from 3 months to 70 years, with a median of 23.5 years. They included 55 males and 37 females. Orthoflavivirus infection was detected in 15 patients (16.3%), classified as confirmed (2 patients, 2.1%) or probable (13 patients, 14.2%) cases. Among probable cases, 6 (6.5%) tested positive for anti-WNV IgM, 5 (5.4%) for anti-DENV IgM, and 2 (2.2%) for both. Ten patients had borderline IgM ELISA results; 7 for WNV (2 of whom also tested positive for DENV) and 3 for DENV (with 1 positive for WNV). No statistically significant associations were found between infection status and demographic factors, clinical, or laboratory findings. Conclusion: Orthoflavivirus infections were identified in 16.3% of undiagnosed AFI patients in Greater Cairo. The study highlights significant diagnostic challenges due to cross-reactivity and potential dual infections. It underscores the need for enhanced surveillance and adoption of advanced and integrated diagnostic approaches to improve the understanding of Orthoflavivirus dynamics in Egypt.