Assessing the impact of insecticide-treated nets in the face of insecticide resistance on malaria control.

The mosquito-borne disease, malaria, continues to impose a devastating health and economic burden worldwide. In malaria-endemic areas, insecticide-treated nets (ITNs) have been useful in curtailing the burden of the disease. However, mosquito resistance to insecticides, decay in ITN efficacy, net attrition, etc., undermine the effectiveness of ITNs in combatting malaria. In this study, mathematical models that account for asymptomatic infectious humans (through a partially immune class or a separate asymptomatic infectious class), insecticide resistance, and decay in ITN efficacy are proposed and analyzed. Analytical and numerical results of the models when ITN efficacy is constant show that there are parameter regimes for which a backward bifurcation occurs. Local and global sensitivity analyses are performed to identify parameters (some of which are potential targets for disease control) with the most significant influence on the control reproduction (R) and disease prevalence. These influential parameters include the maximum biting rate of resistant mosquitoes, ITN coverage, initial ITN efficacy against sensitive mosquitoes, the probability that an infectious mosquito (human) infects a susceptible human (mosquito), and the rate at which adult mosquitoes develop (lose) resistance to insecticides. Simulations of the models show that accounting for asymptomatic infectious humans through a separate class, or not accounting for the decay in ITN efficacy leads to an underestimation of disease burden. In particular, if the initial efficacy of ITNs against sensitive and resistance mosquitoes is 96%, the minimum ITN coverage required to reduce R below one (and hence, contain malaria) is approximately 11% (27%) lower when ITN efficacy is averaged (constant) for a model with a separate asymptomatic class. For the model with a partially immune class and decaying ITN efficacy, reducing R below one is impossible even if the entire populace uses ITNs. The study shows that replacing ITNs before their prescribed lifespans, or designing ITNs with longer lifespans is important for malaria control. Furthermore, the study shows that piperonyl butoxide (PBO) ITNs (which inhibit or reverse insecticide resistance) outperform regular ITNs in malaria control. Hence, prospects for effectively controlling malaria are enhanced by widespread use of high quality ITNs (e.g. PBO ITNs), especially if the useful lifespans of the ITNs are long enough and the ITNs are replaced before the end of their useful lifespans.