Metabolic Signatures of Chikungunya Versus Dengue: A Comparative Study

Background: Chikungunya virus and dengue virus rank among the most clinically significant mosquito-borne pathogens worldwide, imposing substantial disease burdens in endemic regions. Despite their overlapping symptomatology, the diseases diverge markedly in prognosis. This disparity underscores the critical need for tools to differentiate these conditions and elucidate their distinct pathogenic mechanisms. Method: We conducted liquid chromatography–tandem mass spectrometry-based comparative metabolomic analyses to systematically compare plasma profiles from infected individuals. Results: We collected plasma samples from 26 chikungunya fever (CHIKF) patients, 49 dengue fever (DF) patients and 28 healthy individuals. Clinically, CHIKF patients exhibited a higher prevalence of rash (96.3% vs. 36.7%) and involvement of small joints, while DF patients showed prolonged fever and more severe hematological abnormalities. Metabolically, significant differences were observed in specific metabolites, such as eugenol sulfate, lysophosphatidylcholine (14:0/0:0), and piperine, which were dysregulated in both groups compared to healthy controls. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis highlighted unique metabolic perturbations in CHIKF, such as peroxisome proliferator-activated receptor (PPAR) signaling and mechanistic target of rapamycin complex (mTOR) pathways, suggesting potential mechanisms underlying CHIKV-induced arthritis. Conclusions: This study identifies distinct metabolic signatures and functional pathways associated with CHIKF and DF, offering a potential mechanism for differential diagnosis and therapeutic targets. The role of eugenol sulfate in modulating CHIKV-induced arthralgia is particularly promising, supported by its known anti-inflammatory properties.