Towards evolution-proof malaria control with insecticides - PubMed (original) (raw)
Towards evolution-proof malaria control with insecticides
Jacob C Koella et al. Evol Appl. 2009 Nov.
Abstract
As many strategies to control malaria use insecticides against adult mosquitoes, control is undermined by the continual evolution of resistant mosquitoes. Here we suggest that using alternative insecticides, or conventional insecticides in alternative ways might enable effective control, but delay considerably or prevent the evolution of resistance. Our reasoning relies on an epidemiological and an evolutionary principle: (i) the epidemiology of malaria is strongly influenced by the life-span of mosquitoes, as most infected mosquitoes die before the malaria parasite has completed its development; and (ii) evolutionary pressure is strongest in young individuals, for selection on individuals that have completed most of their reproduction has little evolutionary effect. It follows from these principles, first, that insecticides that kill mosquitoes several days after exposure can delay considerably the evolution of resistance and, second, that the evolution of resistance against larvicides can actually benefit control, if it is associated with shorter life-span or reduced biting in adults. If a late-acting insecticide and a larvicide are combined, the evolution of resistance against larvicides can in some circumstances prevent the evolution of resistance against the more effective, late-acting insecticide, leading to sustainable, effective control. We discuss several potential options to create such insecticides, focussing on biopesticides.
Keywords: benefit of resistance; evolution-proof control; insecticide resistance; late-acting insecticide; malaria control.
Figures
Figure 1
Conventional insecticides, that kill exposed mosquitoes shortly after exposure. (A) Measures of the effectiveness of control with a conventional insecticide as a function of the coverage (i.e. the probability that a mosquito is exposed to an insecticide during a bite and assuming that daily mortality is 10% and the probability of infection is 0.3 per bite). The solid line shows the proportion of the emerging mosquitoes that survive to harbour sporozoites and thus become infectious (see Appendix). The dotted line shows the intensity of transmission (expressed as _R_0) up to which malaria is eliminated from the population for a given coverage. This takes into account the two parameters affected by the insecticide: the proportion of infectious mosquitoes and the expected longevity (the term 1/μ in the equation for _R_0) of infectious mosquitoes (Macdonald 1957). The calculation of both terms is described in the Appendix. (B) The evolutionary trajectories of the proportion of resistant individuals in a population with four levels of coverage of the insecticide (shown by the four lines). Note that time is given in the equivalent of gonotrophic cycles (i.e. as a multiple of 3 days). Resistance is assumed to be governed by a single gene, with resistance determined by a dominant allele (i.e. heterozygotes are identical to homozygous resistants). The initial frequency of the resistance-allele was 10−4.
Figure 2
Comparison of late-acting insecticides (with a delay of one to three gonotrophic cycles) and conventional insecticides (with a delay of 0). (A) A measure of the effectiveness of control with a conventional insecticide (solid line) and insecticides that delay their action by one to three gonotrophic cycles as a function of coverage by the insecticide. The _y_-axis shows the intensity of transmission, _R_0, relative to the intensity in the absence of any control. [This is the inverse of the intensity of transmission (expressed as _R_0) up to which malaria is eliminated from the population, see Fig. 1A. Thus the solid curve (for a conventional insecticide) is the inverse of the dotted line of Fig. 1A.] The horizontal lines represent the level of control necessary to eliminate malaria in an area with moderate transmission (_R_0 = 100) and extremely intense transmission (_R_0 = 1000). (B) Evolution of resistance against late-acting insecticides. The circles, connected with thin lines and labelled with _R_0 = 100 and _R_0 = 1000, show the time (as a multiple of gonotrophic cycles) required for resistance to reach 50% of the population at the coverages that would eliminate malaria in areas with moderate and intensive transmission (see panel A). (C) Evolutionary cost of resistance required to block the evolution of resistance. The equations of Fig. 2B are used, except that in resistant mosquitoes fecundity is decreased to F/γ and adult mortality rate is increased to δγ where γ is the cost of resistance (i.e. γ = 1 implies no cost; γ = 2 implies a twofold cost so that fecundity is halved and mortality is doubled). See Appendix for model details.
Figure 3
Larval insecticides. (A) The epidemiological consequence of the evolution of resistance, if resistance is evolutionarily costly. The cost is reflected as a factor γ by which the biting rate of resistant mosquitoes is divided and the adult mortality rate of resistant mosquitoes is multiplied. (Note that a cost with respect to fecundity is not considered, as fecundity has no epidemiological relevance.) The effect of the insecticide in sensitive mosquitoes is given as the proportion of juvenile mosquitoes that are killed by the insecticide. The line shows the combination of the mortality of sensitive larvae and the cost of resistance where _R_0, calculated from the Ross–Macdonald equation, is equal for sensitive (with increased juvenile mortality but no cost) and resistant mosquitoes (with no juvenile mortality but reduced biting rate and increased mortality rate), and the shaded area shows parameters where evolution of resistance increases the effectiveness of control. (B) Evolution of resistance for four levels of insecticide-induced juvenile mortality (shown by the four lines) as a function of the cost of resistance for fecundity and mortality rate. The equations used to calculate the evolutionary response are identical to the ones in Fig. 1, except that (i) juvenile survival of sensitive mosquitoes is decreased by the use of the insecticide, (ii) the mortality rate and fecundity of adult mosquitoes are independent of the insecticide, but in resistant mosquitoes mortality is increased and fecundity decreased by a factor identical to the cost of resistance. (Note that the effect of resistance on biting rate is ignored, for it has no direct effect on evolution.)
References
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