A Systems Biology Framework for Modelling Antimicrobial Resistance Dissemination Across Human, Animal, and Environmental Compartments in Northern Nigeria

Antimicrobial resistance (AMR) operates across interconnected human, animal, and environmental reservoirs in a One Health continuum that cannot be adequately addressed through single-compartment studies. Nigeria's North West and North Central zones, characterized by intense human-livestock co-habitation, open defecation, and pharmaceutical effluent discharge, represent an ideal yet understudied context for systems-level AMR modelling. This study developed and validated a compartmental systems biology model of AMR gene dissemination across human clinical, livestock, and environmental compartments in selected states in northern Nigeria. Empirical resistome data from human clinical isolates, livestock fecal samples, wastewater, and soil were collected from Kano, Kaduna, and Niger States using culture-based and metagenomic approaches. Quantitative AMR gene abundance data served as model parameters for a cross-compartmental differential equation-based transmission model. Sensitivity analysis identified the most influential parameters driving inter-compartmental gene flow. Model simulations predicted that veterinary antibiotic use was the dominant driver of environmental resistome enrichment, contributing 48 percent of modelled gene flux, while pharmaceutical effluent contributed 29 percent and clinical settings contributed 23 percent. Model validation against independent surveillance datasets demonstrated 87 percent predictive accuracy. Scenario modelling showed that simultaneous veterinary antibiotic restriction and hospital effluent treatment would reduce environmental resistome burden by 64 percent over a 10-year horizon. This framework constitutes an original theoretical contribution to One Health AMR modelling in sub-Saharan Africa and provides a quantitative basis for multi-sectoral AMR policy design in northern Nigeria. Keywords: One Health, antimicrobial resistance, systems biology, resistome, northern Nigeria.