Combining fungal biopesticides and insecticide-treated bednets to enhance malaria control

Abstract

In developing strategies to control malaria vectors, there is increased interest in biological methods that do not cause instant vector mortality, but have sublethal and lethal effects at different ages and stages in the mosquito life cycle. These techniques, particularly if integrated with other vector control interventions, may produce substantial reductions in malaria transmission due to the total effect of alterations to multiple life history parameters at relevant points in the life-cycle and transmission-cycle of the vector. To quantify this effect, an analytically tractable gonotrophic cycle model of mosquito-malaria interactions is developed that unites existing continuous and discrete feeding cycle approaches. As a case study, the combined use of fungal biopesticides and insecticide treated bednets (ITNs) is considered. Low values of the equilibrium EIR and human prevalence were obtained when fungal biopesticides and ITNs were combined, even for scenarios where each intervention acting alone had relatively little impact. The effect of the combined interventions on the equilibrium EIR was at least as strong as the multiplicative effect of both interventions. For scenarios representing difficult conditions for malaria control, due to high transmission intensity and widespread insecticide resistance, the effect of the combined interventions on the equilibrium EIR was greater than the multiplicative effect, as a result of synergistic interactions between the interventions. Fungal biopesticide application was found to be most effective when ITN coverage was high, producing significant reductions in equilibrium prevalence for low levels of biopesticide coverage. By incorporating biological mechanisms relevant to vectorial capacity, continuous-time vector population models can increase their applicability to integrated vector management.

Figure 1. Diagram showing the progression of the mosquito population through the stages of the model.

Solid lines show the malaria infection process, dashed lines show the fungal infection process and dotted lines show the gonotrophic feeding process. HS_i and NHS_i refer to the i ^th host-seeking and non-host-seeking stages respectively.

Figure 2. Comparing equilibria obtained by simulation and analytic derivation.

Equilibrium daily EIR as a function of the mean time to death if the fungus is the only mortality source () for different values of the shape parameter and other parameters as in Table 1. For values of the equilibrium daily EIR obtained by analytic derivation (open diamonds) and simulation (black squares) are compared. Sublethal effects of fungal infection on mosquito feeding biology are not incorporated ( & ).

Figure 3. Equilibrium daily EIR and prevalence when the ITN intervention is applied in the absence of the biopesticide.

Equilibrium daily EIR (solid lines) and equilibrium human prevalence (dashed lines) as a function of ITN coverage (). Lines labelled 1 correspond to the ITN intervention parameters in Table 1, and lines labelled 2 correspond to the case where the ITN intervention has no effect on mosquito mortality (other ITN intervention parameters are as in Table 1).

Figure 4. The impact of sublethal effects of fungal infection on mosquito feeding biology.

Equilibrium daily EIR as a function of the mean time to death from fungal infection () for three values of the daily probability of fungal infection (): A, C = 0.1 B, C = 0.5 C, C = 0.9. Lines represent varying sublethal effects of fungal infection on mosquito feeding biology, including no sublethal effects (solid lines), a 25% decrease in the daily probability of finding a blood meal () and a 25% increase in the duration of the non-host-seeking stage () in fungal pathogen-infected mosquitoes (dashed lines), a 50% decrease in and a 50% increase in (dotted lines), and a 75% decrease in and a 75% increase in (dot-dashed lines). Other parameters are given in Table 1.

Figure 5. The effect of varying the period of biopesticide exposure in a given gonotrophic cycle.

Equilibrium daily EIR and equilibrium human prevalence as a function of the daily probability of fungal infection during the period of biopesticide exposure (C_E) for three values of the mean time to death from fungal infection (): A–B. , C–D. , E–F. . Lines represent biopesticide exposure periods (see text) corresponding to (solid lines), (dashed lines) and (dot-dashed lines).

Figure 6. The combined impact of fungal biopesticides and ITNs on human malaria prevalence.

Isolines of the equilibrium human prevalence () for varying ITN coverage () and daily probability of fungal infection during the period of biopesticide exposure (C_E), for different ITN intervention parameters: A. The ITN intervention parameters given in Table 1, B. The ITN intervention does not affect mosquito mortality (other ITN intervention parameters are as in Table 1). The mean time to death from fungal infection is .

Figure 7. Comparing the impact of the combined interventions to the multiplicative effect of both interventions.

The amount by which the equilibrium prevalence deviates from the multiplicative effect of both interventions () as a function of the ITN coverage (). Points represent different ITN intervention parameters, including the parameters given in Table 1 (open circles) and the case where the ITN intervention does not affect mosquito mortality (crosses). All combinations of mean times to death from fungal infection () of , and values of the daily probability of fungal infection during the period of biopesticide exposure (C_E) of C_E = 0.2, 0.4, 0.6 and 0.8, are shown. Panels show different levels of transmission intensity: A. Annual EIR = 47.8, B. Annual EIR = 412.

Figure 8. The effect of the combined interventions on human prevalence for high transmission.

Isolines of the equilibrium human prevalence () for varying ITN coverage () and daily probability of fungal infection during the period of biopesticide exposure (C_E), for different ITN intervention parameters: A. The ITN intervention parameters given in Table 1, B. The ITN intervention does not affect mosquito mortality (other ITN intervention parameters are as in Table 1). The transmission intensity is high (annual EIR = 412). The mean time to death from fungal infection is .

Figure 9. The effect of the combined interventions on human prevalence for low transmission.

Isolines of the equilibrium human prevalence () for varying ITN coverage () and daily probability of fungal infection during the period of biopesticide exposure (C_E). The transmission intensity is low (annual EIR = 1.5). The mean time to death from fungal infection is .