Host-Derived Immune Signatures as Biomarkers to Differentiate Arboviral Acute Febrile Illness from Other Causes of Acute Fever

Background: Arbovirus infections are emerging or re-emerging global health threats due to their raised incidence and geographical spread in endemic regions, as well as the increased risk of local transmission in non-endemic areas. When symptomatic, arbovirus infections usually manifest as acute febrile illnesses (AFI) accompanied by mild, often non-specific symptoms. This non-specific clinical presentation contributes to their misdiagnosis, leading to adverse effects at both the patient and public health levels. Leveraging the potential of host biomarkers as fever triage tools, we assessed their utility for the early identification of arbovirus-associated AFI. Methods: Using multiplex immunoassays (Luminex® or Ella), we retrospectively compared the serum concentrations of 16 immune mediators (CR, PTX3, CCL2, CXCL10, ICAM-1, IFNα, IFNγ, IL-2, IL-4, IL-6, IL-8, IL-10, PCT, TNFα, TRAIL, VCAM-1) and 4 haematological parameters (haemoglobin – Hgb, and leukocyte, erythrocyte and platelet counts). The study population encompassed febrile patients with arboviral infections (Arbo-AFI, n=89) or with fever caused by other infectious conditions (Other-AFI, n=51).