Table_1_Optimal Control of Rat-Borne Leptospirosis in an Urban Environment.docx

Humans acquire leptospirosis through direct contact with animal reservoirs, or more commonly, contact with the environment contaminated with leptospires shed in animal urine. Reservoir populations can be difficult to control through rodenticide application, and resource reduction via habitat management is costly and logistically complicated to implement. When resources are limited, simulation of different combinations of control methods can inform their application in the field. Here we present a framework to find time-dependent control measures for rodent-borne leptospirosis using optimal control mathematical model theory. An age-structured model for leptospire infection in a Norway rat (Rattus norvegicus) population was developed, informed by empirical analyses of data from the city of Salvador, Brazil. We extended this model to include two temporary control measures, rodenticide, and resource reduction, and two permanent control measures, reducing rat carrying capacity and leptospire lifespan in the environment. Optimal control theory seeks the optimum time-dependent controls while taking into account both the cost of the control measures and the “cost” of infection. Multiple control scenarios and the predicted effect of the optimal controls on the population and infection dynamics are presented to illustrate the applications of combinations of temporary and permanent controls. Permanent controls lead to a reduction in prevalence of leptospiral carriage in the rodent population. However, temporary controls can also achieve a reduction in the number of infected rats low enough to reduce risk to humans. Although we focus our modeling on a well-studied species, the Norway rat, our approach can be applied to other disease systems with animal and environmental reservoirs to inform decisions to reduce the risk of human infection.

人类可通过直接接触动物储存宿主感染钩端螺旋体病（leptospirosis），更为常见的感染途径则为接触被动物尿液中排出的钩端螺旋体（leptospires）污染的环境。通过灭鼠剂施用难以控制储存宿主种群，而通过栖息地管理实现资源削减不仅成本高昂，且实施的后勤流程极为复杂。在资源受限的情况下，对不同防控措施组合开展模拟，可为其野外应用提供决策依据。本研究基于最优控制数学模型理论，构建了一套可用于获取鼠源性钩端螺旋体病时间依赖性防控策略的分析框架。本研究以巴西萨尔瓦多市的实证数据分析为依据，构建了褐家鼠（Rattus norvegicus）种群的钩端螺旋体感染年龄结构模型。本研究将该模型拓展为包含两类临时防控措施（灭鼠剂施用、资源削减）以及两类永久防控措施（降低鼠类环境容纳量、缩短环境中钩端螺旋体的存活时长）的扩展模型。最优控制理论可在兼顾防控措施实施成本与感染“成本”的前提下，求解最优的时间依赖性防控策略。本研究设置了多种防控情景，并展示了最优防控策略对种群与感染动态的预测效应，以此阐明临时与永久防控措施组合的应用方式。永久防控措施可降低鼠类种群的钩端螺旋体携带率。但临时防控措施同样可将受感染鼠类的数量降至足够低的水平，从而降低对人类的感染风险。尽管本研究的建模对象为研究较为充分的褐家鼠，但该分析框架可推广至其他存在动物与环境储存宿主的疾病系统，为降低人类感染风险的决策提供参考。