Dose-dependent immune modulation in arboviral coinfections among febrile patients

Background: Arboviruses pose substantial diagnostic and public health challenges in tropical regions where multiple pathogens co-circulate. Nigeria, with diverse ecological zones and limited surveillance infrastructure, represents a critical nexus for arboviral transmission, yet comprehensive data on seroprevalence, coinfection dynamics, immune modulation, and viral genetic diversity remain scarce. Methods: We conducted cross-sectional surveillance across three Nigerian ecological zones from January 2019 to December 2023. Sera from 871 participants were tested for IgG and IgM antibodies to dengue virus (DENV), chikungunya virus (CHIKV), Zika virus (ZIKV), yellow fever virus (YFV), West Nile virus (WNV), and Rift Valley fever virus (RVFV) using immunoblot assays. A stratified subset (n=300) underwent cytokine profiling for interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin-10 (IL-10). IgM-positive samples underwent RT-PCR confirmation with genotype assignment through sequence comparison against GenBank reference strains. Results: Overall IgM seropositivity indicating recent infection was 86.8% (756/871), with DENV most prevalent (59.6%; 95% CI: 56.3-62.8%), followed by CHIKV (49.4%), YFV (48.3%), ZIKV (19.7%), WNV (3.4%), and RVFV (2.3%). Coinfection with two or more arboviruses was detected in 61.2% (533/871) of participants. Seropositivity was highest in the tropical rainforest zone (94.2%) compared with Guinea savanna (84.5%) and Sudan savanna (80.4%; χ²=31.8, p