Indoor residual spray and insecticide-treated bednets for malaria control: theoretical synergisms and antagonisms

Abstract

Indoor residual spray (IRS) of insecticides and insecticide-treated bednets (ITNs) are the two most important malaria vector control tools in the tropical world. Application of both tools in the same locations is being implemented for malaria control in endemic and epidemic Africa. The two tools are assumed to have synergistic benefits in reducing malaria transmission because they both act at multiple stages of the transmission cycle. However, this assumption has not been rigorously examined, empirically or theoretically. Using mathematical modelling, we obtained the conditions for which a combination strategy can be expected to improve upon single control tools. Specifically, spraying of dichlorodiphenyltrichloroethane (DDT) in all houses where residents are not using ITNs can reduce transmission of malaria (R(0)) by up to 10 times more than the reduction achieved through ITNs alone. Importantly, however, we also show how antagonism between control tools can arise via interference of their modes of action. Repellent IRS reduces the likelihood that ITNs are contacted within sprayed houses and ITNs reduce the rate at which blood-fed mosquitoes rest on sprayed walls. For example, 80 per cent coverage of ITNs and DDT used together at the household level resulted in an R(0) of 11.1 when compared with an R(0) of 0.1 achieved with 80 per cent ITN coverage without DDT. While this undesired effect can be avoided using low-repellence pyrethroid chemicals for IRS, the extent of the potential benefits is also attenuated. We discuss the impact that this result will likely have on future efforts in malaria control combination strategy.

Figure 1.

The temporal dynamics of the level of personal protection provided by insecticide-treated bednets (ITNs). The insecticidal property of ITNs decays over time, originating at the maximum level of efficacy (thick, thin and dashed lines correspond to κ values of 1.0, 0.8 and 0.6) and dropping to the minimum level of efficacy, ψ, as provided by the physical barrier of the netting alone (thick, thin and dashed lines correspond to ψ values of 0.3, 0.2 and 0.1). We calculate the decay rate as exp(−τ² × 0.000005) where τ is the time post-impregnation in days. The expression results in an insecticidal half-life of 1 year and a loss of more than 99% insecticidal properties within 3 years, irrespective of initial insecticidal efficacy.

Figure 2.

The distribution strategy for the combined control tools can have profound effects on their efficacy in reducing malaria transmission. (a) Both ITN and DDT coverage are at 80% with initial efficacies of 80%; (b) ITN coverage is at 80% and DDT coverage is at 20% with initial efficacies of 80% for each; and (c) both ITN and pyrethroid spray coverage are at 80% with initial efficacies of 80%. We parametrize corresponding decay rates of DDT and pyrethroid spray as exp(−τ² × 0.00005) and exp(−τ² × 0.00015) to ensure more than 99% loss of insecticidal potency within 12 and 6 months, respectively. ITN and IRS combination strategies: (1) randomly distributing ITNs and IRS; (2) preferentially distributing both together (i.e. IRS first goes to ITN-protected residences, and any surplus IRS goes to non-ITN houses); and (3) preferentially distributing both apart. The qualitative nature of this plot is representative of most parameter values of ITN and IRS combination. Combination 3 is always the most effective strategy followed by strategies 1 and 2, respectively. Dashed line, no control; red line, ITNs only; blue line, IRS only; pink line, combination 1; plus symbols, combination 2; circles, combination 3.

Figure 3.

The optimum DDT coverage for minimizing the R₀ of malaria when used in conjunction with ITNs. Greatest reduction in R₀ results from strategy 3 (preferentially distributing ITN and IRS apart) and γ = (1 − c), irrespective of the initial repellence level and toxicity of the DDT (φ). Results for 80% ITN coverage (c = 0.8) and 80% initial ITN efficacy (κ = 0.8) are presented (other values are shown in the electronic supplementary material, figure S1). Values of φ are as follows: red line, 0; orange line, 0.2; light green line, 0.4; blue line, 0.6; dark blue line, 0.8; black line, 1.0.

Figure 4.

The effects of biannual retreatment of IRS and ITN on the transmission potential of malaria (R₀) and the protected proportion of humans (n) when IRS and ITN are preferentially distributed apart (combination strategy 3). (a) R₀ dynamics with 20% DDT coverage; (b) R₀ dynamics with 80% pyrethroid spray coverage; (c) dynamics of protected proportion of humans (n) with 20% DDT coverage; (d) dynamics of protected proportion of humans (n) with 80% pyrethroid spray coverage. The dashed line refers to ITNs and IRS applied together at months 0, 6, 12, etc., and the black line refers to ITNs applied on months 0, 6, 12, etc., and IRS on months 3, 9, 15, etc. The red line refers to ITNs only.

Figure 5.

Analysis of R₀ sensitivity to control tool-coverage proportions, protective efficacy, mosquito killing efficacies, repellence and insecticide depletion rates. The four scenarios include: ITN re-treatment with either pyrethroid or DDT spray, temporally coinciding or alternating. ‘1’, ‘2’ and ‘3’ refer to random, preferentially together and preferentially separate distributions, respectively. Each control tool value was allowed to vary randomly by 10% within a uniform distribution centred on the standard values. The box corresponds to the 25%, mean and 75% values (whiskers to the 5% and 95% values) of the probability distribution resulting from 1000 runs of a Monte Carlo simulation. (a) IRS and ITN coverage both at 80% and (b) IRS at 20% coverage with ITNs at 80% coverage.