Department of Mathematics, Valdosta State University, Valdosta, Ga 31698, USA.
School of Mathematical and Statistical Sciences, Arizona State University, Tempe, AZ, 85287, USA; Department of Mathematics and Applied Mathematics, University of Pretoria, Pretoria 0002, South Africa.
Math Biosci. 2019 Jun;312:33-49. doi: 10.1016/j.mbs.2019.02.008. Epub 2019 Feb 27.
Although the widespread use of indoors residual spraying (IRS) and insecticides treated bednets (ITNs; later replaced by long-lasting insecticidal nets (LLINs)) has led to a dramatic reduction of malaria burden in endemic areas, such usage has also resulted in the major challenge of the evolution of insecticide resistance in the mosquito population in those areas. Thus, efforts to combat malaria also include the urgent problem of effectively managing insecticide resistance. This study is based on the design and analysis of a new mathematical model for assessing the impact of insecticides resistance in the mosquito population (due to widespread use of IRS and ITNs) on the transmission dynamics and control of malaria in a community. The model, which couples disease epidemiology with vector population genetics, incorporates several fitness costs associated with insecticide resistance. Detailed rigorous analysis of the model is presented. Using data and parameter values relevant to malaria dynamics in moderate and high malaria transmission settings in some parts of Ethiopia, simulations of the model show that, while the ITNs-IRS strategy can lead to the effective control of the disease in both the moderate and high malaria transmission setting if the ITNs coverage level in the community is high enough (regardless of the level of IRS coverage), it fails to manage insecticide resistance (as measured in terms of the frequency of resistant allele at equilibrium in the community). It is further shown that the effective size of the coverage level of the ITNs and IRS required to effectively control the disease, while effectively managing insecticide resistance in the mosquito population, depends on the magnitude of the level of resistant allele dominance (in mosquitoes with heterozygous genotype) and several fitness costs associated with the insecticide resistance in the vector population. For instance, in a moderate transmission setting, malaria burden can be reduced to low levels of endemicity (even with low coverage of ITNs and IRS), and insecticide resistance effectively managed, if the fitness costs of resistance are at their assumed baseline values. Such reduction is not achievable if the fitness costs of resistance are lower than the baseline values.
尽管室内滞留喷洒（IRS）和经杀虫剂处理的蚊帐（ITN；后来被长效杀虫剂处理的蚊帐（LLIN）取代）的广泛使用导致了流行地区疟疾负担的大幅减少，但这种使用也导致了该地区蚊虫种群对杀虫剂产生抗药性的主要挑战。因此，对抗疟疾的努力还包括有效管理杀虫剂抗性这一紧迫问题。本研究基于设计和分析一个新的数学模型，以评估由于广泛使用 IRS 和 ITN 导致的蚊虫种群对疟疾传播动力学和控制的影响。该模型将疾病流行病学与媒介种群遗传学相结合，纳入了与杀虫剂抗性相关的几种适应度成本。对模型进行了详细的严格分析。使用与埃塞俄比亚部分地区中高度疟疾传播环境中疟疾动态相关的数据和参数值，对模型进行了模拟，结果表明，虽然 ITN-IRS 策略如果社区中的 ITN 覆盖率足够高（无论 IRS 覆盖率水平如何），都可以在中高度疟疾传播环境中有效控制疾病，但无法管理杀虫剂抗性（以社区中平衡时抗性等位基因的频率来衡量）。进一步表明，为了有效控制疾病，同时有效地管理蚊虫种群中的杀虫剂抗性，所需的 ITN 和 IRS 覆盖率的有效大小取决于抗性等位基因优势水平（在杂合基因型的蚊子中）和与媒介种群中的杀虫剂抗性相关的几种适应度成本。例如，在中度传播环境中，如果抗性的适应度成本处于假设的基线值，则可以将疟疾负担降低到低流行水平（即使 ITN 和 IRS 的覆盖率较低），并有效地管理杀虫剂抗性。如果抗性的适应度成本低于基线值，则无法实现这种降低。
