Assessing the Theoretical Risk of Plasmodium knowlesi Emergence in Central Africa: A Framework for Zoonotic Surveillance in Potential Novel Spillover Zones

This theoretical framework addresses the critical research gap concerning the potential emergence of *Plasmodium knowlesi*, a zoonotic malaria parasite, in Central Africa. Although currently confined to Southeast Asia, its known capacity for spillover from non-human primates, combined with Central Africa’s extensive forest ecologies and land-use changes, necessitates a proactive risk assessment. The objective is to construct a rigorous, evidence-based framework for evaluating this theoretical risk and guiding future surveillance. The methodology synthesises current knowledge of *P. knowlesi* epidemiology, including its genetic adaptability and documented ecological drivers of zoonotic transmission. This synthesis is logically applied to analyse Central Africa’s specific biogeographical context, potential reservoir hosts among non-human primates, and the bionomics of local *Anopheles* vector species. The central argument posits that the confluence of deforestation, primate habitat fragmentation, and the presence of competent anopheline vectors creates a plausible, albeit unconfirmed, risk scenario for novel spillover. The proposed framework outlines integrated surveillance pillars: monitoring non-human primate populations for plasmodial infections, enhancing vector competence studies, and deploying targeted genomic surveillance within human febrile illness diagnostics. Its significance lies in offering a pre-emptive, regionally focused tool for a neglected threat. Proactive application could enable health systems to mitigate a potential dual malaria burden, thereby safeguarding public health gains and aligning with continental priorities for epidemic preparedness and One Health integration.