High Burden of Coinfections With Epidemic-Prone Pathogens Among Febrile Patients in Nigeria: A Multi-Pathogen Surveillance Study.

BACKGROUND: Characterizing the etiology of acute febrile illness (AFI) remains a critical public health priority in malaria-endemic regions such as Nigeria, where constrained diagnostic capacity frequently contributes to misdiagnosis and delays in outbreak detection and response. This study aimed to explore the burden and nature of pathogen coinfections among febrile patients and to assess whether coinfection patterns were associated with clinical or epidemiologic differences. METHODS: Patients presenting with AFI at tertiary hospitals in north-central and southern Nigeria were screened for 25 pathogens using the TaqMan Array Card multi-pathogen polymerase chain reaction. Enrollment was conducted over a 12-month period at each site, August 2023 to September 2024. The analysis focused on the pathogen distribution in coinfections and any associated outcomes for coinfected patients. RESULTS: Among the 1200 participants enrolled, 20 pathogens were detected in 57.9% of enrollees. Coinfections were detected in 12.6%. Among them, 2 pathogens were detected in 36.0% and 3 or 4 pathogens were detected in 1.2%. Nearly all coinfections included either Plasmodium or Rickettsia. Notably, coinfected patients were not clinically distinguishable from those with single-pathogen infections based on severity of the illness, presence of underlying health conditions, or risk behaviors such as use of mosquito nets. Among those with viral hemorrhagic fevers, those with coinfections exhibited a notably higher case fatality rate (11.5%) than those with single-pathogen infections (4.2%). CONCLUSIONS: Given the challenge of clinically distinguishing between infections with overlapping symptomology, there is an urgent need for multi-pathogen diagnostics for clinical and public health use.