Preliminary Genetic Characterization of Enteroviruses in Pediatric HFMD Cases: First Data from Jeddah, Saudi Arabia

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a prevalent contagious viral illness primarily affecting children under five years old globally, with potential for severe complications. It a common pediatric illness primarily caused by enteroviruses (EV), yet data on its epidemiology and viral diversity in Saudi Arabia remain scarce. This study addresses this knowledge gap by providing the first molecular prevalence data for HFMD in Saudi Arabia, aiming to determine the genomic serotypes of enterovirus (EV) infections in pediatric HFMD cases and investigate their association with disease outcome. METHODS: Thirty-four pediatric patients clinically diagnosed with HFMD in Jeddah between November 2023 and June 2024 were enrolled. Oral and throat swabs were analyzed using real-time RT-PCR using broad-spectrum EV detection and conventional RT-PCR targeting the 5'-noncoding regions, followed by Sanger sequencing and phylogenetic analysis for comprehensive serotype identification. RESULTS: Of the 34 cases, enteroviruses were detected in 82.35% (28/34) of cases. The majority of cases were male (64.7%) and under six years old (61.67%), with a median age of 4.88 ± 3.19 years. Clinical symptoms predominantly included typical rashes on the head, face, and limbs (96.67%), fever (73.53%), and skin itchiness (58.82%). Sequence analysis based on 5'-NCR identified five EV serotypes: CV-A6 (50%), CV-A16 (35.7%), CV-A10 (7.1%), EV-A71 (3.6%), and CV-A5 (3.6%). CV-A6 was the predominant serotype and detected across all age groups, with the highest subtype diversity in children ≤ 3 years. Phylogenetic analysis revealed that Saudi strains were closely related to global isolates, especially from Asia and Europe, suggesting multiple introductions and localized transmission. CONCLUSION: This pilot study reveals substantial genetic diversity and co-circulation of multiple EV serotypes among HFMD cases in Jeddah. The predominance of CV-A6 aligns with recent global trends, underscoring the need for ongoing molecular surveillance and public health preparedness, including vaccine strategy development targeting emerging serotypes.