昆虫抗药性的治理策略:一个数学模型的提出

本文用计算机模型分析及评价了昆虫抗药性的三种治理策略:顺序轮用,“高杀死”策略及棋盘式用药.假设昆虫具有一定的生物学特性:如抗性为单基因,单抗性,抗性基因为半显性,两性生殖,昆虫有扩散习性,感性系在不施药情况下有微弱的适应优势等.分析了用不同剂量造成的不同的死亡率,不同的反选择作用,不同的基因稀释作用等情况对三个策略的影响.结果显示出,在这些情况下,用3—5种杀虫剂隔代顺序轮用加上微弱的反选择作用是最为有效的.“高杀死”策略加上一定的稀释作用也极为有效.棋盘式用药在特殊情况下才有用.     

Delayed action insecticides and their role in mosquito and malaria control

There is considerable interest in the management of insecticide resistance in mosquitoes. One possible approach to slowing down the evolution of resistance is to use late-life-acting (LLA) insecticides that selectively kill only the old mosquitoes that transmit malaria, thereby reducing selection pressure favoring resistance. In this paper we consider an age-structured compartmental model for malaria with two mosquito strains that differ in resistance to insecticide, using an SEI approach to model malaria in the mosquitoes and thereby incorporating the parasite developmental times for the two strains. The human population is modeled using an SEI approach. We consider both conventional insecticides that target all adult mosquitoes, and LLA insecticides that target only old mosquitoes. According to linearised theory the potency of the insecticide affects mainly the speed of evolution of resistance. Mutations that confer resistance can also affect other parameters such as mean adult life span and parasite developmental time. For both conventional and LLA insecticides the stability of the malaria-free equilibrium, with only the resistant mosquito strain present, depends mainly on these other parameters. This suggests that the main long term role of an insecticide could be to induce genetic changes that have a desirable effect on a vital parameter such as adult life span. However, when this equilibrium is unstable, numerical simulations suggest that a potent LLA insecticide can slow down the spread of malaria in humans but that the timing of its action is very important.     

Insecticides in host-parasitoid interactions

The equilibrium and local stability properties are described of insect host-parasitoid models that include the effects of insecticide application. The models are framed in discrete time making it important to distinguish between different sequences of parasitism and insecticide kill in the host's life cycle. Four possibilities are considered: (1) Insecticides act prior to parasitism and only kill hosts. (2) Insecticides act after parasitism and only kill hosts. (3) Insecticides act after parasitism and also kill parasitized hosts at the same rate. (4) Insecticides act prior to parasitism and also kill adult parasitoids. There is a clear ranking of the different application strategies in terms of their effect on the depression of the host equilibrium and their contribution to stability.     

Implications of gene amplification for evolution and management of insecticide resistance

Simulations were used to compare evolution of insecticide resistance predicted by a conventional two-allele model with predictions from three- and four-allele models that assume resistance is based on gene amplification. Results were similar between models when insecticide concentration was low or moderate. In contrast, when 10% of the population was not exposed to insecticide each generation, high insecticide concentrations slowed resistance development in the two-allele model, but caused rapid development of high levels of resistance in the three- and four-allele models. The presence of a third allele at an initial frequency as low as 10-7 doubled or tripled the rate of resistance development in some cases. Attempts to slow evolution of resistance by overwhelming it with high concentrations of insecticides are not likely to succeed if gene amplification or other mechanisms generate alleles that confer high levels of resistance.     

抗马拉硫磷淡色库蚊不同基因型的自然内禀增长率及其对抗性演化的影响

本文涉及淡色库蚊(Culex pipiens pallens)抗马拉硫磷纯合子(RR)、杂合子(RS)和敏感纯合子(SS)的自然内禀增长率及其对马拉硫磷抗性演化的影响。RR、RS和SS的内禀增长率分别为0.1118、0.1171和0.1339。RR和RS基因型在无杀虫剂时呈现出繁殖不利性,RR和RS的相对适合度分别是SS的0.65和0.68。 影响淡色库蚊对马拉硫磷进化的某些因子在计算机上进行了模拟。模拟的因子包括R等位基因的起始频率(P_o)、所用马拉硫磷的剂量和迁入率(m)。模拟结果表明(I)不用药时R等位基因衰减是由于RR和RS基因型的繁殖不利性;(2)在起始种群N_o=200,P_o=0.1,使用杀死全部SS和RS的剂量(8ppm)处理,使R等位基因为有效隐性,并且m≥0.15时可阻止马拉硫磷抗性的发生。     

Evolution of insecticide resistance in Culex pipiens populations: The Corsican paradox

Culex pipiens mosquitoes from Corsica have been subject to insecticide treatments since 1971, using temephos (an organophosphate). After 17 years, resistance has not developed beyond a 14-fold level. This relatively low resistance is due to the presence of several identified resistance genes, including the insensitive target ( Ace^R ) and overproduced esterases (A1, A4 and B4). The fact that only a low resistance has developed after 17 years of treatment and that this low resistance level is the result of a relatively large number of resistance genes constitute a paradox. To understand this situation and explain why a higher temephos resistance level has not evolved in Corsica as in other parts of the world, it is proposed that the occurrence (through mutation or migration) of efficient resistance genes was a limiting step, and that the only resistance genes available at that time through migration from the surrounding Mediterranean countries had a low cross-resistance to temephos. The local situation of Corsica is discussed in the light of recent data on the world distribution of the known organophosphate resistance genes in this species, and the relative role of mutation and migration in the evolution of insecticide resistance in natural populations.     

Combining zooprophylaxis and insecticide spraying: a malaria-control strategy limiting the development of insecticide resistance in vector mosquitoes

Strategies to eradicate the vector-borne infectious diseases (e.g. malaria and Japanese encephalitis) are often directed at controlling vectors with insecticides. Spraying insecticide, however, opens the way for the development of insecticide resistance in vectors, which may lead to the failure of disease control. In this paper, we examine whether the combined use of insecticide spray and zooprophylaxis can limit the development of insecticide resistance in mosquitoes. Zooprophylaxis refers to the control of vector-borne diseases by attracting vectors to domestic animals in which the pathogen cannot amplify (a dead-end host). The human malaria parasite Plasmodium spp. has a closed transmission cycle between humans and mosquitoes, and hence cattle can serve as a dead-end host. Our model reveals that, by a suitable choice of insecticide spraying rate and cattle density and location, malaria can, in some situations, be controlled without mosquitoes developing insecticide resistance.     

The importance of modelling the spread of insecticide resistance in a heterogeneous environment: the example of adding synergists to bed nets

ABSTRACT: BACKGROUND: Insecticides are an effective and practical tool for reducing malaria transmission but the development of resistance to the insecticides can potentially compromise controls efforts. In this study a mathematical model was developed to explore the effects on mosquito populations of spatial heterogeneous deployment of insecticides. This model was used to identify important parameters in the evolution of insecticide resistance and to examine the contribution of new generation long-lasting insecticidal bed nets, that incorporate a chemical synergist on the roof panel, in delaying insecticide resistance. METHODS: A genetic model was developed to predict changes in mosquito fitness and resistance allele frequency. Parameters describing insecticide selection, fitness cost and the additional use of synergist were incorporated. Uncertainty and sensitivity analysis were performed followed by investigation of the evolution of resistance under scenarios of fully effective or ineffective synergists. RESULTS: The spread of resistance was most sensitive to selection coefficients, fitness cost and dominance coefficients while mean fitness was most affected by baseline fitness levels. Using a synergist delayed the spread of resistance but could, in specific circumstances that were thoroughly investigated, actually increase the rate of spread. Different spread dynamics were observed, with simulations leading to fixation, loss and most interestingly, equilibrium (without explicit overdominance) of the resistance allele. CONCLUSIONS: This strategy has the potential to delay the spread of resistance but note that in an heterogeneous environment it can also lead to the opposite effect, i.e., increasing the rate of spread. This clearly emphasizes that selection pressure acting inside the house cannot be treated in isolation but must be placed in context of overall insecticide use in an heterogeneous environment.     

The effects of age, exposure history and malaria infection on the susceptibility of Anopheles mosquitoes to low concentrations of pyrethroid

Chemical insecticides are critical components of malaria control programs. Their ability to eliminate huge numbers of mosquitoes allows them to swiftly interrupt disease transmission, but that lethality also imposes immense selection for insecticide resistance. Targeting control at the small portion of the mosquito population actually responsible for transmitting malaria parasites to humans would reduce selection for resistance, yet maintain effective malaria control. Here, we ask whether simply lowering the concentration of the active ingredient in insecticide formulations could preferentially kill mosquitoes infected with malaria and/or those that are potentially infectious, namely, old mosquitoes. Using modified WHO resistance-monitoring assays, we exposed uninfected Anopheles stephensi females to low concentrations of the pyrethroid permethrin at days 4, 8, 12, and 16 days post-emergence and monitored survival for at least 30 days to evaluate the immediate and long-term effects of repeated exposure as mosquitoes aged. We also exposed Plasmodium chabaudi- and P. yoelii-infected An. stephensi females. Permethrin exposure did not consistently increase mosquito susceptibility to subsequent insecticide exposure, though older mosquitoes were more susceptible. A blood meal slightly improved survival after insecticide exposure; malaria infection did not detectably increase insecticide susceptibility. Exposure to low concentrations over successive feeding cycles substantially altered cohort age-structure. Our data suggest the possibility that, where high insecticide coverage can be achieved, low concentration formulations have the capacity to reduce disease transmission without the massive selection for resistance imposed by current practice.     

Mosquito carboxylesterases: a review of the molecular biology and biochemistry of a major insecticide resistance mechanism

The major mechanism of organophosphorus insecticide resistance in Culex mosquitoes involves the elevation of one or more esterases. The general mechanism underlying this resistance is the amplification of the structural genes. This review covers the classification of the mosquito esterases in the context of classical esterase nomenclature. The function of the amplified esterases and the structure of the amplified DNA on which they occur are also described. Implications of information on the esterase amplicons are discussed in relation to the evolution and migration of insecticide resistance in Culex.     

The biology of insecticidal activity and resistance

Identifying insecticide resistance mechanisms is paramount for pest insect control, as the understandings that underpin insect control strategies must provide ways of detecting and managing resistance. Insecticide resistance studies rely heavily on detailed biochemical and genetic analyses. Although there have been many successes, there are also many examples of resistance that still challenge us. As a precursor to rational pest insect control, the biology of the insect, within the contexts of insecticide modes of action and insecticide metabolism, must be well understood. It makes sense to initiate this research in the best model insect system, Drosophila melanogaster, and translate these findings and methodologies to other insects. Here we explore the usefulness of the D. melanogaster model in studying metabolic-based insecticide resistances, target-site mediated resistances and identifying novel insecticide targets, whilst highlighting the importance of having a more complete understanding of insect biology for insecticide studies.     

Insect immunity and its implication in mosquito-malaria interactions

Insects' resistance to infectious agents is essential for their own survival and also for the health of the plant, animal and human populations with which they closely interact. Several of the major human diseases are spread by insects and are rapidly expanding as a result of the development of insecticide resistance in vectors and drug resistance in parasites. A vector insects' permissiveness to a pathogen, and hence the spread of the disease, will largely depend on the compatibility of the molecular interactions between the two species and the capability of the insect immune system to recognize and kill the pathogen. The innate immune system comprises a variety of components and mechanisms that can discriminate between different microorganisms and mount specific responses to control pathogenic infections. An impressive body of knowledge on the insects' innate immunity has been generated from studies in the model organism Drosophila. These studies are now guiding the exploration of the immune system in the vector mosquito of human malaria, Anopheles, and its implication in the elimination of parasites. Anopheles immune responses have been linked to parasite losses and some refractory mosquitoes can kill all parasites through specific defence mechanisms. The recently sequenced Drosophila and Anopheles genomes provide a detailed and comparative view on their immune gene repertoires that in combination with post-genomic analyses is used to further dissect the complex mechanisms of Plasmodium killing in the mosquito.     

Evolution of resistance with sequential application of insecticides in time and space

The effect, on the evolution of resistance, of alternating two unrelated insecticides in space or in time (or both) is studied. Transient polymorphism is shown to occur under certain conditions of mating, selection and migration. In some situations, the transient polymorphism can show a sharp decline before the alleles recover to fixation. Alternating a single insecticide in space, and in space and time, is also considered. Neither alternation in space nor in time shows any advantage with regard to delaying the onset of resistance. The most promising mode is to alternate the presence and absence of a single insecticide in both space and time, especially if it is applied at the larval stage and if some form of biological control is used in the regions where no insecticide is applied.     

Fitness costs of an insecticide resistance and their population dynamical consequences in the oriental fruit fly

Naled is a commonly used insecticide for controlling populations of the oriental fruit fly, Bactrocera dorsalis (Hendel), in Taiwan and other countries. B. dorsalis has developed resistance to the insecticide, and the resistance management is an important issue. Ecological effects (e.g., fitness costs) of the resistance, when fully understood, can be used for the resistance management. This study examined the effects of the insecticide resistance on important life history traits (i.e., survival rates, stage durations, and fecundity) of the oriental fruit fly by comparing the traits of insecticide resistant individuals and susceptible individuals. Population dynamical properties were also examined using a stage-structured matrix model that was parameterized with the empirical data. The results revealed that susceptible individuals had shorter stage durations (e.g., grew faster) and reproduced more than resistant individuals. The average longevity of sexually mature susceptible adults was longer than that of sexually mature resistant adults. The matrix population model predicted that a population of the susceptible individuals would grow faster than a population of the resistant individuals in the absence of the insecticide. The sensitivity analysis of the model suggests that the sexually immature adult stage is a good candidate for controlling B. dorsalis populations.     

Evaluating reproductive fitness and metabolic costs for insecticide resistance in Myzus persicae from Chile

The development of insecticide resistance in pest insects is an increasing problem for agriculture, forestry and public health. Aphids are ubiquitous herbivorous insects, with approximately 4700 known species, of which less than 5% exploit the agricultural environment successfully. Of these, the peach‐potato aphid Myzus persicae Sulzer is recognized as one of the most important pests worldwide because it has acquired resistance to many insecticides. Although resistance to insecticides provides important benefits for pests in agricultural fields that are treated with insecticides, it may be associated with fitness (or other) costs in environments that are insecticide free. In the present study, the fitness and energy costs that might be experienced by M. persicae in an insecticide‐free environment when carrying at least one insecticide resistance mutation (IRM), or by having an increased production of esterases, are evaluated. The study investigates whether genotypes that have an IRM also have enhanced esterase production, whether there is any metabolic cost associated with insecticide resistance, and whether there are any fitness costs associated with insecticide resistance and metabolic expenditure. The intrinsic rate of increase, standard metabolic rate (i.e. a measure of maintenance costs) and constitutive esterase activity are determined for 30 different multilocus genotypes carrying (or not carrying) at least one of the two most frequent insecticide resistance mutations (MACE and kdr/super‐kdr) that occur in Chile. The results show that genotypes carrying at least one IRM have higher levels of total esterase activity than genotypes without an IRM, that there is no evidence of an energy cost associated with total esterase activity or IRM, and no evidence for a reproductive fitness cost associated with total esterase activity, IRM or metabolic rate. The results agree with previous studies showing linkage disequilibrium between insecticide resistance mechanisms, although they contrast with those of studies that report fitness costs associated with insecticide resistance in Myzus persicae.     

Effect of extended diapause on evolution of resistance to transgenic Bacillus thuringiensis corn by northern corn rootworm (Coleoptera: Chrysomelidae)

We develop a population genetics model for the northern corn rootworm, Diabrotica barberi Smith & Lawrence, to examine the effect of extended diapause on the evolution of resistance to transgenic Bacillus thuringiensis (Bt) corn, Zea mays L. We model conditions found in the center of the extended diapause problem along the Minnesota-South Dakota-Iowa borders. The proportion of resistance alleles in eggs oviposited after 15 simulated years is used to measure the evolution of resistance. Sensitivity analysis indicates that although population genetics parameters (fecundity, initial egg density, density-dependent larval survival, random mating, insecticide mortality, and gene expression) affect the evolution of resistance, product characteristics (e.g., Bt toxin dose) and farmer management practices (e.g., insecticide use on refuge corn and rotation pattern) generally have a larger impact on the development of resistance. Exceptions to this generalization exist: 1) if the resistance allele is dominant, resistance evolves quickly; 2) the level of random mating is an important determinant of how quickly resistance evolves for a theoretical high dose product; and 3) small differences in insecticide mortality imply large differences in resistance for medium- and low-dose products with high levels of Bt corn adoption and a predominance of 1- and 2-yr corn rotations. When extended diapause spreads into a new area, it typically reduces resistance to Bt corn, assuming Bt corn is used only on continuous corn. In the study region where extended diapause already exists, increasing extended diapause (increasing hatch rates after two or three winters while holding total hatch constant), tends to increase resistance because the resistance increasing effect of the hatch rate after two winters dominates the resistance decreasing effect of the hatch rate after three winters. However, this is not always the case, because combinations of rotation pattern, toxin dose, and soil insecticide use exist for which the net effect of extended diapause decreases resistance. Results are interpreted as a combination of two offsetting effects. First, extended diapause injects older alleles with lower resistance allele frequencies into the breeding population, which slows resistance. Second, extended diapause speeds the population's recovery from perturbations (reduces the undercompensating density dependence of population dynamics), which accelerates resistance.     

Interactions between Pesticide Genes: Model and Experiment

In response to years of intense selection pressure by organophosphate insecticides, several different insecticide resistance mechanisms have evolved in natural populations of the mosquito Culex pipiens. We examined interactions between two of the most important mechanisms using a four-compartment model of insecticide pharmacokinetics. The joint effect of different mechanisms of resistance can be expressed in terms of epistasis at the physiological level in this model. The type of epistasis predicted by the model depends on the particular physiological mechanisms of resistance involved. Resistance due to a reduced penetration of the insecticide combines multiplicatively with other resistance factors, but resistance due to detoxicative processes and to insensitivity of the target site combines additively. How the pattern of epistasis at the physiological level is translated into fitness epistasis in natural populations of this mosquito depends on the intensity and pattern of insecticide selection in the field.     

斜纹夜蛾抗药性及其防治对策的研究进展

斜纹夜蛾Spodopteralitura是多种作物的重要害虫 ,对有机氯、有机磷、氨基甲酸酯类、拟除虫菊酯类以及Bt制剂等杀虫剂均产生抗药性。本文对斜纹夜蛾抗药性的形成与发展、抗性机理及其防治对策等方面进行了综述     

Dieldrin-resistant cabbage root fly in England

The existence of dieldrin resistance in Erioischia brassicae has been investigated in the main areas in England and Wales where brassicas are grown for human consumption. Dieldrin-susceptible and dieldrin-resistant flies were collected and bred as separate strains in the laboratory. In toxicity tests adult flies were treated with topically applied doses of insecticide in microdrops of cellosolve, and larvae were dipped in solutions of insecticide in 70% acetone and 30% water. Adults of the laboratory resistant strain showed a high level of resistance to dieldrin and aldrin and a lower level of resistance to γ-BHC. There was no cross-resistance with chlorfenvinphos or diazinon. Larvae of the resistant strain were shown to be resistant to dieldrin. Dieldrin resistance has been found in four areas in southern England, but not in a fifth major area, and resistant flies did not increase as rapidly in some areas as others. Sufficient migration of flies appeared to take place to produce similar percentages of resistant flies over areas of several square miles, but considerable differences were found in fly populations about 10 miles apart. It is suggested that the speed of development of insecticide resistance is affected by the proportion of brassica crops which are treated in an area, the amounts of insecticide applied to individual crops, and hence the insecticidal pressure applied to the E. brassicae population.     

Population dynamics and "outbreaks" of diamondback moth (Lepidoptera: Plutellidae) in Guangdong province, China: climate or failure of management?

Diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), became the major pest of Brassica vegetable production in Guangdong, a province in southeastern China, in the late 1980s and has continued to challenge growers, particularly during the spring and autumn. Control has relied on insecticides and, as has happened in other parts of the world, resistance to these has evolved and subsequent field control failures have occurred. We review and summarize the history of diamondback moth management in Guangdong. We show that the geographic distribution of the pest in China is well described by a simple climate niche model. Our model predicts the seasonal phenology and some of the variation in abundance among years in Guangdong. Discrepancies may reflect migration and insecticide use at a landscape level. The scale of the pest problem experienced varies with management practices. Local production breaks, and strict post harvest hygiene are associated with lower pest pressure on large-scale production units. As more and more insecticides become ineffective the need to implement an insecticide resistance management strategy, as well as basic integrated pest management practices, will become more pressing. The potential use and development of a better forecasting system for diamondback moth that will assist these developments is outlined.