Integrative Genomic and Epidemiological Analysis of Monkeypox Virus Clade IIb Transmission Dynamics in Nigeria: Building a Predictive Outbreak Risk Model

Nigeria's re-emergence as the endemic origin of the globally spreading Mpox clade IIb lineage from 2017 onwards positions Nigerian virological research as central to global Mpox preparedness. Despite this, the within-Nigeria transmission dynamics, spillover frequency from reservoir animals, and drivers of outbreak amplification remain inadequately modelled. This study conducts an integrative genomic and epidemiological analysis of Mpox clade IIb transmission dynamics in Nigeria and constructs a predictive outbreak risk model. A national retrospective study will collate all confirmed Mpox cases in Nigeria from 2017 to 2025 from NCDC records, supplemented by newly collected specimens from ongoing endemic transmission sites in Bayelsa, Delta, Rivers, and Lagos states. Whole genome sequencing of at least 150 new Nigerian isolates will be performed using Oxford Nanopore Technology. Bayesian phylodynamic analysis will reconstruct transmission networks, estimate effective population size dynamics, and identify transmission amplification events. An ecological niche model using MaxEnt will map rodent reservoir habitat suitability across Nigeria's ecological zones. A stochastic individual-based outbreak risk model incorporating human network structure, vaccination coverage with modified vaccinia Ankara, sexual transmission parameters, and animal contact rates will be parameterised and validated against historical outbreak data. This study contributes a theoretically original and empirically grounded predictive risk framework for Mpox outbreak risk in Nigeria, providing the NCDC and WHO with a decision-support tool for resource allocation and targeted vaccination strategy. Keywords: Monkeypox virus, clade IIb, phylodynamics, outbreak risk model, Nigeria