Insecticide Control of Vector-Borne Diseases: When Is Insecticide Resistance a Problem?

Many of the most dangerous human diseases are transmitted by insect vectors. After decades of repeated insecticide use, all of these vector species have demonstrated the capacity to evolve resistance to insecticides. Insecticide resistance is generally considered to undermine control of vector-transmitted diseases because it increases the number of vectors that survive the insecticide treatment. Disease control failure, however, need not follow from vector control failure. Here, we review evidence that insecticide resistance may have an impact on the quality of vectors and, specifically, on three key determinants of parasite transmission: vector longevity, competence, and behaviour. We argue that, in some instances, insecticide resistance is likely to result in a decrease in vector longevity, a decrease in infectiousness, or in a change in behaviour, all of which will reduce the vectorial capacity of the insect. If this effect is sufficiently large, the impact of insecticide resistance on disease management may not be as detrimental as previously thought. In other instances, however, insecticide resistance may have the opposite effect, increasing the insect's vectorial capacity, which may lead to a dramatic increase in the transmission of the disease and even to a higher prevalence than in the absence of insecticides. Either way—and there may be no simple generality—the consequence of the evolution of insecticide resistance for disease ecology deserves additional attention

Costs and benefits of sub-lethal Drosophila C Virus infection

Viruses are major evolutionary drivers of insect immune systems. Much of our knowledge of insect immune responses derives from experimental infections using the fruit fly Drosophila melanogaster. Most experiments, however, employ lethal pathogen doses through septic injury, frequently overwhelming host physiology. While this approach has revealed several immune mechanisms, it is less informative about the fitness costs hosts may experience during infection in the wild. Using both systemic and oral infection routes we find that even apparently benign, sub-lethal infections with the horizontally transmitted Drosophila C Virus (DCV) can cause significant physiological and behavioral morbidity that is relevant for host fitness. We describe DCV-induced effects on fly reproductive output, digestive health, and locomotor activity, and we find that viral morbidity varies according to the concentration of pathogen inoculum, host genetic background and sex. Notably, sub-lethal DCV infection resulted in a significant increase in fly reproduction, but this effect depended on host genotype. We discuss the relevance of sub-lethal morbidity for Drosophila ecology and evolution, and more broadly, we remark on the implications of deleterious and beneficial infections for the evolution of insect immunity

Natural infection by the protozoan Leptomonas wallacei impacts the morphology, physiology, reproduction, and lifespan of the insect Oncopeltus fasciatus

Trypanosomatids are protozoan parasites that infect thousands of globally dispersed hosts, potentially affecting their physiology. Several species of trypanosomatids are commonly found in phytophagous insects. Leptomonas wallacei is a gut-restricted insect trypanosomatid only retrieved from Oncopeltus fasciatus. The insects get infected by coprophagy and transovum transmission of L. wallacei cysts. The main goal of the present study was to investigate the effects of a natural infection by L. wallacei on the hemipteran insect O. fasciatus, by comparing infected and uninfected individuals in a controlled environment. The L. wallacei-infected individuals showed reduced lifespan and morphological alterations. Also, we demonstrated a higher infection burden in females than in males. The infection caused by L. wallacei reduced host reproductive fitness by negatively impacting egg load, oviposition, and eclosion, and promoting an increase in egg reabsorption. Moreover, we associated the egg reabsorption observed in infected females, with a decrease in the intersex gene expression. Finally, we suggest alterations in population dynamics induced by L. wallacei infection using a mathematical model. Collectively, our findings demonstrated that L. wallacei infection negatively affected the physiology of O. fasciatus, which suggests that L. wallacei potentially has a vast ecological impact on host population growth

Timing malaria transmission with mosquito fluctuations.

Temporal variations in the activity of arthropod vectors can dramatically affect the epidemiology and evolution of vector-borne pathogens. Here, we explore the "Hawking hypothesis", which states that these pathogens may evolve the ability to time investment in transmission to match the activity of their vectors. First, we use a theoretical model to identify the conditions promoting the evolution of time-varying transmission strategies in pathogens. Second, we experimentally test the "Hawking hypothesis" by monitoring the within-host dynamics of <i>Plasmodium relictum</i> throughout the acute and the chronic phases of the bird infection. We detect a periodic increase of parasitemia and mosquito infection in the late afternoon that coincides with an increase in the biting activity of its natural vector. We also detect a positive effect of mosquito bites on <i>Plasmodium</i> replication in the birds both in the acute and in the chronic phases of the infection. This study highlights that <i>Plasmodium</i> parasites use two different strategies to increase the match between transmission potential and vector availability. We discuss the adaptive nature of these unconditional and plastic transmission strategies with respect to the time scale and the predictability of the fluctuations in the activity of the vector

Insecticide resistance and malaria transmission by Culex pipiens mosquitoes

L'évolution de la résistance aux insecticides chez les moustiques responsables de la transmission de maladies infectieuses compromet notre capacité à contrôler ces populations de vecteurs et pose de graves problèmes de santé publique. Mais les nombreuses modifications physiologiques associées au phénomène de résistance aux insecticides pourraient altérer l'épidémiologie de ces maladies de manière plus indirecte en modifiant la capacité vectorielle des moustiques. Afin d'étudier cette question nous avons mis en place un nouveau système expérimental composé du parasite aviaire Plasmodium relictum SGS1 et de son vecteur naturel le moustique Culex pipiens. Nous avons étudié l'effet de différents allèles de résistance aux insecticides (représentant deux mécanismes principaux i.e. la résistance métabolique ou la modification de la cible) sur une série de traits d'histoire de vie du parasite et du moustique. L'impact de ces différents allèles a été étudié d'une part, dans les conditions contrôlées de leur expression dans un même fond génétique (en utilisant plusieurs souches de moustiques isogéniques), et d'autre part, dans les conditions plus réalistes de leur expression dans un fond génétique hétérogène (utilisation de moustiques échantillonnés sur le terrain). Nous montrons que la résistance aux insecticides a des effets pleïotropes sur l'immunocompétence et les traits d'histoire de vie des moustiques. Son effet sur le développement de Plasmodium semble en revanche limité. Nous discutons d'une part, de la nécessité de poursuivre une approche multifactorielle (impliquant la physiologie, l'immunité et le comportement des moustiques) afin de mieux comprendre l'impact de la résistance aux insecticides sur la transmission de Plasmodium, et d'autre part des perspectives intéressantes qu'offrent ce nouveau système expérimental pour l'étude de l'écologie évolutive des maladies à vecteurs.The evolution of insecticide resistance in mosquitoes threatens our ability to control many-vector-transmitted diseases, thereby raising serious public health issues. Insecticide resistance entails numerous physiological changes in mosquitoes. This thesis investigates whether these physiological changes alter the quality of mosquitoes as vectors of malaria. To address this issue, we developed a new experimental system consisting in the avian malaria parasite Plasmodium relictum SGS1 and its natural vector, the mosquito Culex pipiens. We investigated the impact of two insecticide resistance mechanisms (target site resistance and metabolic resistance) on several mosquito and parasite life history traits relevant for malaria transmission. The effect of different insecticide resistant genes was investigated using both isogenic laboratory mosquito strains (i.e. against a homogeneous genetic background) and sympatric field caught mosquitoes (i.e. under the more realistic, albeit noisier, conditions of a heterogeneous genetic background). We show that insecticide resistance has a pleiotropic effect on several mosquito traits (immunocompetence, longevity, fecundity), whereas it has only a limited effect on Plasmodium development. We discuss, on the one hand, the need to pursue such a multi-factorial approach (combining the mosquito physiology, immunity and behavior) to better understand the impact of insecticide resistance on malaria transmission and, on the other hand, the promising perspectives offered by this new experimental system for studying the evolutionary-ecology of infectious diseases

Energetic cost of insecticide resistance in Culex pipiens mosquitoes

The extensive use of insecticides to control vector populations has lead to the widespread development of different mechanisms of insecticide resistance. Mutations that confer insecticide resistance are often associated to fitness costs that prevent them from spreading to fixation. In vectors, such fitness costs include reductions in preimaginal survival, adult size, longevity, and fecundity. The most commonly invoked explanation for the nature of such pleiotropic effects of insecticide resistance is the existence of resource-based trade-offs. According to this hypothesis, insecticide resistance would deplete the energetic stores of vectors, reducing the energy available for other biological functions and generating trade-offs between insecticide resistance and key life history traits. Here we test this hypothesis by quantifying the energetic resources (lipids, glycogen, and glucose) of larvae and adult females of the mosquito Culex pipiens L. resistant to insecticides through two different mechanisms: esterase overproduction and acetylcholinesterase modification. We find that, as expected from trade-off theory, insecticide resistant mosquitoes through the overproduction of esterases contain on average 30% less energetic reserves than their susceptible counterparts. Acetylcholinesterase-modified mosquitoes, however, also showed a significant reduction in energetic resources (20% less). We suggest that, in acetylcholinesterase-modified mosquitoes, resource depletion may not be the result of resource-based trade-offs but a consequence of the hyperactivation of the nervous system. We argue that these results not only provide a mechanistic explanation for the negative pleiotropic effects of insecticide resistance on mosquito life history traits but also can have a direct effect on the development of parasites that depend on the vector's energetic reserves to fulfil their own metabolic needs

Insecticide resistance and malaria transmission : infection rate and oocyst burden in Culex pipiens mosquitoes infected with Plasmodium relictum

Background: The control of most vectors of malaria is threatened by the spread of insecticide resistance. One factor that has been hitherto largely overlooked is the potential effects of insecticide resistance on the ability of mosquitoes to transmit malaria: are insecticide-resistant mosquitoes as good vectors of Plasmodium as susceptible ones? The drastic physiological changes that accompany the evolution of insecticide resistance may indeed alter the ability of vectors to transmit diseases, a possibility that, if confirmed, could have major epidemiological consequences. Methods: Using a novel experimental system consisting of the avian malaria parasite (Plasmodium relictum) and its natural vector (the mosquito Culex pipiens), two of the most common mechanisms of insecticide resistance (esterase overproduction and acetylcholinesterase modification) were investigated for their effect on mosquito infection rate and parasite burden. For this purpose two types of experiments were carried out using (i) insecticideresistant and susceptible laboratory isogenic lines of Cx. pipiens and (ii) wild Cx. pipiens collected from a population where insecticide resistant and susceptible mosquitoes coexist in sympatry. Results: The isogenic line and wild-caught mosquito experiments were highly consistent in showing no effect of either esterase overproduction or of acetylcholinesterase modification on either the infection rate or on the oocyst burden of mosquitoes. The only determinant of these traits was blood meal size, which was similar across the different insecticide resistant categories in both experiments. Conclusions: Insecticide resistance was found to have no effect on Plasmodium development within the mosquito. This is the first time this question has been addressed using a natural mosquito-Plasmodium combination, while taking care to standardize the genetic background against which the insecticide resistance genes operate. Infection rate and oocyst burden are but two of the factors that determine the vectorial capacity of mosquitoes. Other key determinants of parasite transmission, such as mosquito longevity and behaviour, or the parasite's incubation time, need to be investigated before concluding on whether insecticide resistance influences the ability of mosquitoes to transmit malaria