Emergence Of Insecticide Resistance Research Articles

Pharmacological validation of an inward-rectifier potassium (Kir) channel as an insecticide target in the yellow fever mosquito Aedes aegypti.

Mosquitoes are important disease vectors that transmit a wide variety of pathogens to humans, including those that cause malaria and dengue fever. Insecticides have traditionally been deployed to control populations of disease-causing mosquitoes, but the emergence of insecticide resistance has severely limited the number of active compounds that are used against mosquitoes. Thus, to improve the control of resistant mosquitoes there is a need to identify new insecticide targets and active compounds for insecticide development. Recently we demonstrated that inward rectifier potassium (Kir) channels and small molecule inhibitors of Kir channels offer promising new molecular targets and active compounds, respectively, for insecticide development. Here we provide pharmacological validation of a specific mosquito Kir channel (AeKir1) in the yellow fever mosquito Aedes aegypti. We show that VU590, a small-molecule inhibitor of mammalian Kir1.1 and Kir7.1 channels, potently inhibits AeKir1 but not another mosquito Kir channel (AeKir2B) in vitro. Moreover, we show that a previously identified inhibitor of AeKir1 (VU573) elicits an unexpected agonistic effect on AeKir2B in vitro. Injection of VU590 into the hemolymph of adult female mosquitoes significantly inhibits their capacity to excrete urine and kills them within 24 h, suggesting a mechanism of action on the excretory system. Importantly, a structurally-related VU590 analog (VU608), which weakly blocks AeKir1 in vitro, has no significant effects on their excretory capacity and does not kill mosquitoes. These observations suggest that the toxic effects of VU590 are associated with its inhibition of AeKir1.

Effective autodissemination of pyriproxyfen to breeding sites by the exophilic malaria vector Anopheles arabiensis in semi-field settings in Tanzania.

BackgroundMalaria vector control strategies that target adult female mosquitoes are challenged by the emergence of insecticide resistance and behavioural resilience. Conventional larviciding is restricted by high operational costs and inadequate knowledge of mosquito-breeding habitats in rural settings that might be overcome by the juvenile hormone analogue, Pyriproxyfen (PPF). This study assessed the potential for Anopheles arabiensis to pick up and transfer lethal doses of PPF from contamination sites to their breeding habitats (i.e. autodissemination of PPF).MethodsA semi-field system (SFS) with four identical separate chambers was used to evaluate PPF-treated clay pots for delivering PPF to resting adult female mosquitoes for subsequent autodissemination to artificial breeding habitats within the chambers. In each chamber, a tethered cow provided blood meals to laboratory-reared, unfed female An. arabiensis released in the SFS. In PPF-treated chambers, clay pot linings were dusted with 0.2 – 0.3 g AI PPF per pot. Pupae were removed from the artificial habitats daily, and emergence rates calculated. Impact of PPF on emergence was determined by comparing treatment with an appropriate control group.ResultsMean (95% CI) adult emergence rates were (0.21 ± 0.299) and (0.95 ± 0.39) from PPF-treated and controls respectively (p < 0.0001). Laboratory bioassay of water samples from artificial habitats in these experiments resulted in significantly lower emergence rates in treated chambers (0.16 ± 0.23) compared to controls 0.97 ± 0.05) (p < 0.0001). In experiments where no mosquitoes introduced, there were no significant differences between control and treatment, indicating that transfer of PPF to breeding sites only occurred when mosquitoes were present; i.e. that autodissemination had occurred. Treatment of a single clay pot reduced adult emergence in six habitats to (0.34 ± 0.13) compared to (0.98 ± 0.02) in the controls (p < 0.0001), showing a high level of habitats coverage amplification of the autodissemination event.ConclusionThe study provides proof of principle for the autodissemination of PPF to breeding habitats by malaria vectors. These findings highlight the potential for this technique for outdoor control of malaria vectors and call for the testing of this technique in field trials.

Facing the Resistance Crisis in Malaria Control by Developing and Evaluating 'Resistance-Breaking' Products

Prevention of malaria is best achieved by controlling the mosquito vector which, today in Africa relies almost entirely on the use of residual insecticides inside the home. Wide scale implementation of tools such as indoor residual spraying (IRS) and long lasting insecticide impregnated bednets (LLINs) have led to impressive decreases in malaria transmission in some regions and these interventions are the cornerstone of malaria control programmes in most African countries. These two interventions are largely reliant on a single class of insecticides, the pyrethroids. Only pyrethroids can be used to treat bednets and, although four insecticide classes are approved by the World Health Organisation for use in IRS, the vast majority of programmes spray with pyrethroids. An inevitable consequence of the scale up of malaria control has been the emergence of insecticide resistance in the Anopheles vectors. Pyrethroid resistance was first detected in Anopheles gambiae in West Africa in 1993 and remained relatively rare until the end of the twentieth century. But in the past 10 years reports of pyrethroid resistance in the major African malaria vectors have escalated. Action must be taken to ensure that this resistance does not compromise malaria control. The AvecNet project (www.avecnet.eu) was established in 2011, with funding from the European Union Framework 7 programme, with the goal of developing new or improved mosquito control tools to complement existing interventions and control insecticide resistant populations. Some of the key activities and outputs from this project are described.

Forewing Shape Variability Between Sexes and Across Populations of the Rice Bug, Leptocorisa varicornis Fabricius (1803) Using Geometric Morphometrics

Leptocorisa varicornis (F.) (1803) rice bug is a serious pest of rice. Misidentification of this pest had led to non-effective management strategies resulting to possible emergence of insecticide resistance. Proper identification of this species is necessary in developing effective management strategies against this pest, and correct identification needs accurate examination of the insect’s morphology. Geometric morphometrics (GM) statistically analyzes shape variability allowing better understanding of the nature and variability of the insect in relation to the evolvability of characters and its possible implications to adaptability of the organism. This study made use of GM to determine forewing shape variability between sexes and across populations of L. varicornis (F.) from selected localities in Northern Mindanao, Philippines. Exploratory results initially showed that variations between sexes were generally characterized by differences in overall shape of forewing, apex and wing base. Variations across populations were associated largely with differences in overall forewing shape, contour of inner margin, and shape of wing base. Series of confirmatory tests obtained highly significant results, which all confirmed presence of intersexual and interpopulation variations in L. varicornis. Environmental stressors like seasonal cropping, flood and application of pesticides might influence differences in forewings of rice bugs since rice bugs have to fly to long distance after cropping or change location when existing habitat conditions are no longer suitable for their survival. Thorough understanding of the biological basis of the observed variations is essential for the effective control against this species.  Keywords: environmental stressors, insect, insect’s morphology, intersexual variations, pest. Â

Efficacy of phytosterol as mosquito larvicide

To the editors, Mosquitoes are the most important vectors in terms of global public health. They transmits most of the life threatening diseases like malaria, yellow fever, dengue fever, chikungunya ferver, filariasis, encephalitis, West Nile virus etc., mostly in tropical and subtropical countries of the world. Emergence of insecticide resistance and the necessity of preservation of natural health of ecosystem recommended the use of biological products in vector control operations. They are biodegradable, target specific, eco-friendly and there are no evidences of resistance development. Phytosterols are steroid compounds similar to cholesterol that are found in plants. Exploiting nutritional requirements, such as cholesterol, offers a novel, target-specific and environmentally friendly approach are important for mosquito control. Cholesterol is used in cell membranes and is a precursor of molting hormone. In mosquitoes, it is vital for growth, development and egg production. Mosquitoes can't produce cholesterol in their body and generate cholesterol by metabolizing ingested plant sterols in their guts. Mosquitoes take the sterol from the plant decays during their larval stage in the form of phytosterol, which is then converted to cholesterol. This conversion occurs by a sterol carrier protein (SCP). Phytosterols can be uses in vector control operations in following ways. a) Some noxious phytosterols produce larval mortality after their consumption. For instance, the steroid β-sitosterol, isolated from leaves of Abutilon indicum (Linn.) Sweet exhibited toxicity to larval forms of Aedes aegypti (Ae. aegypti) (LC50=11.5 mg/L), Culex quinquefasciatus (LC50=26.7 mg/L) and Anopheles stephensi (LC50=3.58 mg/L)[1]. A phytosteroid, isolated from the leaves of Cestrum diurnum was previously reported for its toxic activity against Culex quinquefasciatus[2]. Another steroid, β-sitosterol-3-O-β-D-glucoside also exhibited potent mosquitocidal activity against adult Ae. aegypti[3]. b) Mosquito populations can also be controlled by plant-based inhibitors, which inhibit SCP activity. Due to the inhibition of SCP, mosquitoes can't produce chlosterol from plant sterols and results in developmental deformities lead to larval death. Ee et al., isolated mangostin, an inhibitor of SCP, which was toxic against Ae. aegypti[4]. Today, the environmental safety is considered to be of paramount importance. Application of phytosterol as dietary supplement or SCP inhibitor may serve as relatively safe, inexpensive, and are readily available option in mosquito control programme.

Nano particles of herbal origin: A recent eco-friend trend in mosquito control

To the editor, Vector control is an essential requirement in control of epidemic diseases such as malaria, filariasis, dengue that are transmitted by different species of mosquitoes. Emergence of insecticide resistance and harmful effect on non-target organisms and environment necessitated an urgent search for development of new and improved mosquito control methods that are economical and effective as well as safe for non-target organisms and the environment. Insecticides of synthesized natural products, such as silver, gold or silicon nano-particles of herbal origin become a priority in this search. The word “nano” is derived from a Greek word meaning “dwarf”. In technical terms, the word “nano” means 10−9, or one billionth of a meter. Targeted nanoparticles exhibit many novel characteristic features, such as extra ordinary strength, more chemical reactivity, magnetic properties and or high electrical conductivity. “Nano-technology” deals with application of such particles in biological, physical, chemical, environmental, agricultural, industrial or pharmaceutical science. At present, a number of physical, chemical, biological, and hybrid methods are available to synthesize different types of silver, gold, silicon, zinc and platinum nanoparticles. Although physical and chemical methods are more popular and widely used for synthesis of nanoparticles, the related environmental toxicity and non biodegradable nature of the products limited their applications. So, the “green” route for nanoparticle synthesis from herbal origin is of great interest due to eco-friendliness, economic prospects, feasibility and wide range of applications[1]. Nano technology has a wide application in vector control in the form of nanocapsules for herbicide delivery and vector and pest management and nanosensors for pest detection[2]. Synthesized silver or gold nanoparticles also help to produce new insecticides and insect repellants. Applications of nano technology have been extended in the field of mosquito control by the synthesis of silver/gold nano particles from environmentally acceptable plant extract and eco-friendly reducing and capping agents. The characterization and the structure determination of these nano particles also become possible through the application of modern scientific instruments such as UV–VIS spectroscopy, Fourier Transform Infrared Spectroscopy, X-ray Diffraction, Scanning and Transmission Electron Microscopy, which also advocates for its wider application. Green synthesis of nanoparticles are also used in the molecular level where gene silencing triggered by dsRNA or small interfering RNA, siRNA have been also practiced in mosquito control operations. The use of “green” processes for the synthesis of nanoparticles is a new and rapidly developing branch of nanotechnology. However, knowledge of the bioactivity of nanoparticles against mosquitoes and malaria parasites is limited. Rajakumar et al. reported the use of silver nano particles synthesized from leaf extract of Eclipta prostrata, to control 4th instar larvae of Culex quinquefasciatus (Cx. quinquefasciatus) and Anopheles subpictus (An. subpictus)[3]. The synthesized particles' size was 35-60 nm. The highest mortality was calculated at 24 h in synthesized silver nano particles against Cx. quinquefasciatus (LC50=4.56 mg/L; LC90=13.14 mg/L) than An. subpictus (LC50=5.14 mg/L; LC90=25.68 mg/L). Sareen et al. had reported the larvicidal efficacy of silver nano particles synthesized from aqueous leaf extract of Hibiscus rosasinensis against the larvae of Aedes albopictus[4]. After 12 hours of exposure, 50% mortality was observed and after 16 hours of treatment, 90% mortality was calculated in 1.0 mg/L. 100% mortality was recorded in 5.0 mg/L of silver nano particles after 3 hours of exposure. Santhoshkumar et al. studied synthesis of Silver nano particles using Nelumbo nucifera leaf extract and its larvicidal activity was judged against Cx. quinquefasciatus and An. subpictus[5]. The maximum efficiency was observed against the larvae of An. subpictus (LC50=0.69 mg/L; LC90=2.15 mg/L) compared to Cx. quinquefasciatus (LC50=1.10 mg/L; LC90=3.59 mg/L). Jayaseelan et al. observed the larvicidal potentiality of synthesized silver nano particles using leaf aqueous extract of Tinospora cordifolia Miers against An. subpictus and Cx. quinquefasciatus[6]. The maximum efficacy was found against the larvae of An. subpictus (LC50=6.43 mg/L). Haldar et al. synthesized highly stable nanoparticles of metallic silver with average dimension of 26.6 nm by a simple, cost-effective, reproducible and previously unexploited biogenic source viz. dried green fruits of Drypetes roxburghii (Wall) and reported its mosquito larvicidal activity against Anopheles stephensi and Cx. quinquefasciatus[7]. The larvicidal potential of silver nanoparticles synthesized using fungus Cochliobolus lunatus against two species of mosquitoes Aedes aegypti and Anopheles stephensi Liston have been reported by Salunkhe et al[8]. These results reveal that the green, biological synthesis of silver/gold nano particles have the potential to be utilized as a good, rapid, eco-friendly approach for the control of mosquito population. It is totally a new pathway but can be effectively utilized for the efficient killing of mosquitoes.

Escherichia coli expressing a green fluorescent protein (GFP) in Anopheles stephensi: a preliminary model for paratransgenesis

Issues, like emerging insecticide resistance in Anopheles mosquitoes, have led to a breakdown in many vector control programs. In this study, a recombinant Escherichia coli with plasmid expressing a green fluorescent protein (E.coli-GFP) was used as a paratransgenesis model to determine: the possibility of E. coli-GFP trans-stadial transmission. The effect of the water microflora, of bacteria-impregnated sugar solutions, and of blood-feeding on E. coli-GFP colonization and localization within An. stephensi tissues, were studied. The results demonstrated the persistence of E. coli-GFP during molting and metamorphosis events and its trans-stadial transmission. Also the efficacy of bacteria-impregnated sugar solutions for transferring the bacteria to the adult mosquito’s midgut was shown. A blood meal dramatically increased the number of bacteria within 24–48 h post feeding. In addition to fluorescence microscope evaluation, GFP gene PCR amplification showed the presence of the bacteria in the midgut of larvae, pupae, and adults up to 13 days after eclosion. Massive colonization of bacteria was observed in the larvae and in the adult mosquito’s malpighian tubules which may play a role in retaining bacteria in adult mosquitos. The results of this study showed that E. coli could be used as a laboratory model in paratransgenesis studies for the evaluation of various effector molecules as anti-parasite agents for malaria and filariasis.

Kaolin spraying protects cotton plants against damages by boll weevil Anthonomus grandis Boheman (Coleoptera: Curculionidae)

The high cost of insecticides, the emergence of insecticide resistance in populations of a number of insect species and other problems arising from their continuous use, such as biological imbalance, cotton fiber waste, and environmental pollution, have prompted the development of new technologies aiming the control of Anthonomus grandis Boheman in cotton crops. This study evaluated the level of protection conferred by kaolin clay foliar spraying to cotton plants against boll weevil damage. Treatment-tested spraying kaolin or endosulfan on cotton plants. The highest percentage of oviposition-punctured squares were observed in the control, and the lowest percentages in the treatments sprayed with endosulfan and kaolin in a systematic manner and where the boll weevil reached the economic threshold at all assessments. The greatest numbers of non-attacked bolls by weevils and cotton-seed yield were observed under the endosulfan treatments, followed by the treatments of kaolin spraying. The smallest number of bolls and lowest cotton-seed yield were observed for the control plots. These finding are of practical significance because they may reduce the cotton production cost and environmental impacts of chemical pesticides and make possible the production of organic cotton with the presence of boll weevils.

Exploiting the behaviour of wild malaria vectors to achieve high infection with fungal biocontrol agents.

BackgroundControl of mosquitoes that transmit malaria has been the mainstay in the fight against the disease, but alternative methods are required in view of emerging insecticide resistance. Entomopathogenic fungi are candidate alternatives, but to date, few trials have translated the use of these agents to field-based evaluations of their actual impact on mosquito survival and malaria risk. Mineral oil-formulations of the entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana were applied using five different techniques that each exploited the behaviour of malaria mosquitoes when entering, host-seeking or resting in experimental huts in a malaria endemic area of rural Tanzania.ResultsSurvival of mosquitoes was reduced by 39-57% relative to controls after forcing upward house-entry of mosquitoes through fungus treated baffles attached to the eaves or after application of fungus-treated surfaces around an occupied bed net (bed net strip design). Moreover, 68 to 76% of the treatment mosquitoes showed fungal growth and thus had sufficient contact with fungus treated surfaces. A population dynamic model of malaria-mosquito interactions shows that these infection rates reduce malaria transmission by 75-80% due to the effect of fungal infection on adult mortality alone. The model also demonstrated that even if a high proportion of the mosquitoes exhibits outdoor biting behaviour, malaria transmission was still significantly reduced.ConclusionsEntomopathogenic fungi strongly affect mosquito survival and have a high predicted impact on malaria transmission. These entomopathogens represent a viable alternative for malaria control, especially if they are used as part of an integrated vector management strategy.

Insecticide Resistance and the Future of Malaria Control in Zambia

BackgroundIn line with the Global trend to improve malaria control efforts a major campaign of insecticide treated net distribution was initiated in 1999 and indoor residual spraying with DDT or pyrethroids was reintroduced in 2000 in Zambia. In 2006, these efforts were strengthened by the President's Malaria Initiative. This manuscript reports on the monitoring and evaluation of these activities and the potential impact of emerging insecticide resistance on disease transmission.MethodsMosquitoes were captured daily through a series of 108 window exit traps located at 18 sentinel sites. Specimens were identified to species and analyzed for sporozoites. Adult Anopheles mosquitoes were collected resting indoors and larva collected in breeding sites were reared to F1 and F0 generations in the lab and tested for insecticide resistance following the standard WHO susceptibility assay protocol. Annual cross sectional household parasite surveys were carried out to monitor the impact of the control programme on prevalence of Plasmodium falciparum in children aged 1 to 14 years.ResultsA total of 619 Anopheles gambiae s.l. and 228 Anopheles funestus s.l. were captured from window exit traps throughout the period, of which 203 were An. gambiae malaria vectors and 14 An. funestus s.s.. In 2010 resistance to DDT and the pyrethroids deltamethrin, lambda-cyhalothrin and permethrin was detected in both An. gambiae s.s. and An. funestus s.s.. No sporozoites were detected in either species. Prevalence of P. falciparum in the sentinel sites remained below 10% throughout the study period.ConclusionBoth An. gambiae s.s. and An. funestus s.s. were controlled effectively with the ITN and IRS programme in Zambia, maintaining a reduced disease transmission and burden. However, the discovery of DDT and pyrethroid resistance in the country threatens the sustainability of the vector control programme.

Lethal and pre-lethal effects of a fungal biopesticide contribute to substantial and rapid control of malaria vectors.

Rapidly emerging insecticide resistance is creating an urgent need for new active ingredients to control the adult mosquitoes that vector malaria. Biopesticides based on the spores of entomopathogenic fungi have shown considerable promise by causing very substantial mortality within 7–14 days of exposure. This mortality will generate excellent malaria control if there is a high likelihood that mosquitoes contact fungi early in their adult lives. However, where contact rates are lower, as might result from poor pesticide coverage, some mosquitoes will contact fungi one or more feeding cycles after they acquire malaria, and so risk transmitting malaria before the fungus kills them. Critics have argued that ‘slow acting’ fungal biopesticides are, therefore, incapable of delivering malaria control in real-world contexts. Here, utilizing standard WHO laboratory protocols, we demonstrate effective action of a biopesticide much faster than previously reported. Specifically, we show that transient exposure to clay tiles sprayed with a candidate biopesticide comprising spores of a natural isolate of Beauveria bassiana, could reduce malaria transmission potential to zero within a feeding cycle. The effect resulted from a combination of high mortality and rapid fungal-induced reduction in feeding and flight capacity. Additionally, multiple insecticide-resistant lines from three key African malaria vector species were completely susceptible to fungus. Thus, fungal biopesticides can block transmission on a par with chemical insecticides, and can achieve this where chemical insecticides have little impact. These results support broadening the current vector control paradigm beyond fast-acting chemical toxins.

The emergence of insecticide resistance in central Mozambique and potential threat to the successful indoor residual spraying malaria control programme

BackgroundMalaria vector control by indoor residual spraying was reinitiated in 2006 with DDT in Zambézia province, Mozambique. In 2007, these efforts were strengthened by the President's Malaria Initiative. This manuscript reports on the monitoring and evaluation of this programme as carried out by the Malaria Decision Support Project.MethodsMosquitoes were captured daily through a series of 114 window exit traps located at 19 sentinel sites, identified to species and analysed for sporozoites. Anopheles mosquitoes were collected resting indoors and tested for insecticide resistance following the standard WHO protocol. Annual cross sectional household parasite surveys were carried out to monitor the impact of the control programme on prevalence of Plasmodium falciparum in children aged 1 to 15 years.ResultsA total of 3,769 and 2,853 Anopheles gambiae s.l. and Anopheles funestus, respectively, were captured from window exit traps throughout the period. In 2010 resistance to the pyrethroids lambda-cyhalothrin and permethrin and the carbamate, bendiocarb was detected in An. funestus. In 2006, the sporozoite rate in An. gambiae s.s. was 4% and this reduced to 1% over 4 rounds of spraying. The sporozoite rate for An. funestus was also reduced from 2% to 0 by 2008. Of the 437 Anopheles arabiensis identified, none were infectious. Overall prevalence of P. falciparum in the sentinel sites fell from 60% to 32% between October 2006 and October 2008.ConclusionBoth An. gambiae s.s. and An. funestus were controlled effectively with the DDT-based IRS programme in Zambézia, reducing disease transmission and burden. However, the discovery of pyrethroid resistance in the province and Mozambique's policy change away from DDT to pyrethroids for IRS threatens the gains made here.

Dengue vector control strategies in an urban setting: an economic modelling assessment

An estimated 2·5 billion people are at risk of dengue. Incidence of dengue is especially high in resource-constrained countries, where control relies mainly on insecticides targeted at larval or adult mosquitoes. We did epidemiological and economic assessments of different vector control strategies. We developed a dynamic model of dengue transmission that assesses the evolution of insecticide resistance and immunity in the human population, thus allowing for long-term evolutionary and immunological effects of decreased dengue transmission. We measured the dengue health burden in terms of disability-adjusted life-years (DALYs) lost. We did a cost-effectiveness analysis of 43 insecticide-based vector control strategies, including strategies targeted at adult and larval stages, at varying efficacies (high-efficacy [90% mortality], medium-efficacy [60% mortality], and low-efficacy [30% mortality]) and yearly application frequencies (one to six applications). To assess the effect of parameter uncertainty on the results, we did a probabilistic sensitivity analysis and a threshold analysis. All interventions caused the emergence of insecticide resistance, which, with the loss of herd immunity, will increase the magnitude of future dengue epidemics. In our model, one or more applications of high-efficacy larval control reduced dengue burden for up to 2 years, whereas three or more applications of adult vector control reduced dengue burden for up to 4 years. The incremental cost-effectiveness ratios of the strategies for two high-efficacy adult vector control applications per year was US$615 per DALY saved and for six high-efficacy adult vector control applications per year was $1267 per DALY saved. Sensitivity analysis showed that if the cost of adult control was more than 8·2 times the cost of larval control then all strategies based on adult control became dominated. Six high-efficacy adult vector control applications per year has a cost-effectiveness ratio that will probably meet WHO's standard for a cost-effective or very cost-effective intervention. Year-round larval control can be counterproductive, exacerbating epidemics in later years because of evolution of insecticide resistance and loss of herd immunity. We suggest the reassessment of vector control policies that are based on larval control only. The Fulbright Programme, CAPES (Brazilian federal agency for post-graduate education), the Miriam Burnett trust, and the Notsew Orm Sands Foundation.

Bedbugs and Infectious Diseases

Bedbugs are brown and flat hematophagous insects. The 2 cosmopolite species, Cimex lectularius and Cimex hemipterus, feed on humans and/or domestic animals, and recent outbreaks have been reported in occidental countries. Site assessment for bedbug eradication is complex but can be assured, despite emerging insecticide resistance, by hiring a pest-control manager. The common dermatological presentation of bites is an itchy maculopapular wheal. Urticarial reactions and anaphylaxis can also occur. Bedbugs are suspected of transmitting infectious agents, but no report has yet demonstrated that they are infectious disease vectors. We describe 45 candidate pathogens potentially transmitted by bedbugs, according to their vectorial capacity, in the wild, and vectorial competence, in the laboratory. Because of increasing demands for information about effective control tactics and public health risks of bedbugs, continued research is needed to identify new pathogens in wild Cimex species (spp) and insecticide resistance.

Exploiting the behaviour of wild malaria vectors to achieve high infection with entomopathogenic fungus

Background Control of mosquito vectors has been the mainstay in the fight against malaria, but alternatives are required in view of emerging insecticide resistance. Entomopathogenic fungi have proven to be such an alternative, but to date, very few trials have translated use of these agents to field-based evaluations of their impact on mosquito survival and malaria risk. Delivery techniques that successfully infect mosquitoes need to be developed and tested under field conditions.

Learning Concepts in Evolution Using Malaria as a Case Study

OPEN ACCESSMay 11, 2010Learning Concepts in Evolution Using Malaria as a Case Study Aditi Pai, PhD Aditi Pai, PhD Spelman College Google Scholar More articles by this author https://doi.org/10.15766/mep_2374-8265.8086 SectionsAbout ToolsDownload Citations ShareFacebookTwitterEmail AbstractThe primary aim of this resource is to promote student understanding of the importance of evolutionary theory to medicine. This module uses malaria as a case study for learning basic concepts in evolutionary biology by using examples in which malaria acts as an evolutionary force. In the first of the four case study assignments, students learn about malaria as a selective agent on human populations. In the second week, the assignment is designed to allow students to make connections between concepts in population genetics by learning about sickle cell allele frequency in various human populations. In the latter two assignments, another evolution story related to malaria (i.e., that of drug resistance in malaria parasites) is explored. Instructors may also use the emergence of insecticide resistance in malaria vector mosquitoes as a topic for additional assignments. At the end of the fourth exercise, students are asked to articulate the importance of evolutionary theory in medicine.Survey results revealed that students at Spelman College appreciate this structure and the materials in the case study. Specifically, the aims of the assessment were to determine if this pedagogical approach was interesting or useful to the students, effective in improving students' knowledge, and effective in enhancing students' learning experience compared to a traditional biology class. The results of these three assessment activities revealed that students rated their interest in case-study work to be high and indicated that their subject knowledge was significantly enhanced. A comparison of students' evaluation of their learning experiences in the old and the new case-study-based introductory biology class, even with the same instructor, showed that they rated their learning to be significantly better in the case-study-based class. The data suggest that the case study based approach was more effective in engaging students and enhancing their learning. Educational Objectives By the end of the module, the learner will be able to: List conditions for natural selection to take place.Discuss how natural selection acts on individuals but evolution is seen at a population level.Predict whether the mutation will spread or not when given the nature of a mutation and the nature of the environment it is in.Explain how drug resistance arises in malaria parasites.Predict what would happen if infected people or mosquitoes moved from populations with drug resistant malaria, to populations without drug resistant parasites.Propose solutions to controlling malaria using evolutionary thinking.Provide two examples of how evolutionary thinking is relevant to disease management. Sign up for the latest publications from MedEdPORTAL Add your email below FILES INCLUDEDReferencesRelatedDetails FILES INCLUDED Included in this publication: Instructor Notes for Malaria and Evolution case.doc Malaria and Evolution Case Instructor Version.ppt Malaria and Evolution Case Student Version.ppt To view all publication components, extract (i.e., unzip) them from the downloaded .zip file. Download editor’s noteThis publication may contain technology or a display format that is no longer in use. CitationPai A. Learning Concepts in Evolution Using Malaria as a Case Study. MedEdPORTAL. 2010;6:8086. https://doi.org/10.15766/mep_2374-8265.8086 Copyright & Permissions© 2010 Pai. This is an open-access publication distributed under the terms of the Creative Commons Attribution-NonCommercial-Share Alike license.KeywordsHardy- WeinbergSalariaMCATGene ExpressionSickle CellGeneticsCase StudyToxicologyEvolutionGene FlowDrug ResistanceNatural Selection Disclosures The authors received a HHMI grant to develop this course for Spelman College and an AAMC grant to develop this manuscript. Funding/Support None to report. Prior Presentations Presented at: Fall Conference of National Center for Case Study Teaching in Science. Institutional Resarch and Academic Career Development Awards Conference; June 2007. Loading ...

Transmission blocking vaccines to control insect-borne diseases: a review.

Insect-borne diseases are responsible for severe mortality and morbidity worldwide. As control of insect vector populations relies primarily on the use of insecticides, the emergence of insecticide resistance as well to unintended consequences of insecticide use pose significant challenges to their continued application. Novel approaches to reduce pathogen transmission by disease vectors are been attempted, including transmission-blocking vaccines (TBVs) thought to be a feasible strategy to reduce pathogen burden in endemic areas. TBVs aim at preventing the transmission of pathogens from infected to uninfected vertebrate host by targeting molecule(s) expressed on the surface of pathogens during their developmental phase within the insect vector or by targeting molecules expressed by the vectors. For pathogen-based molecules, the majority of the TBV candidates selected as well as most of the data available regarding the effectiveness of this approach come from studies using malaria parasites. However, TBV candidates also have been identified from midgut tissues of mosquitoes and sand flies. In spite of the successes achieved in the potential application of TBVs against insect-borne diseases, many significant barriers remain. In this review, many of the TBV strategies against insect-borne pathogens and their respective ramification with regards to the immune response of the vertebrate host are discussed.

Transcriptome response to pollutants and insecticides in the dengue vector Aedes aegypti using next-generation sequencing technology

BackgroundThe control of mosquitoes transmitting infectious diseases relies mainly on the use of chemical insecticides. However, mosquito control programs are now threatened by the emergence of insecticide resistance. Hitherto, most research efforts have been focused on elucidating the molecular basis of inherited resistance. Less attention has been paid to the short-term response of mosquitoes to insecticides and pollutants which could have a significant impact on insecticide efficacy. Here, a combination of LongSAGE and Solexa sequencing was used to perform a deep transcriptome analysis of larvae of the dengue vector Aedes aegypti exposed for 48 h to sub-lethal doses of three chemical insecticides and three anthropogenic pollutants.ResultsThirty millions 20 bp cDNA tags were sequenced, mapped to the mosquito genome and clustered, representing 6850 known genes and 4868 additional clusters not located within predicted genes. Mosquitoes exposed to insecticides or anthropogenic pollutants showed considerable modifications of their transcriptome. Genes encoding cuticular proteins, transporters, and enzymes involved in the mitochondrial respiratory chain and detoxification processes were particularly affected. Genes and molecular mechanisms potentially involved in xenobiotic response and insecticide tolerance were identified.ConclusionsThe method used in the present study appears as a powerful approach for investigating fine transcriptome variations in genome-sequenced organisms and can provide useful informations for the detection of novel transcripts. At the biological level, despite low concentrations and no apparent phenotypic effects, the significant impact of these xenobiotics on mosquito transcriptomes raise important questions about the 'hidden impact' of anthropogenic pollutants on ecosystems and consequences on vector control.

Why is it important to study malaria epidemiology in India?

Malaria is a major vector-borne disease in India. Based on vast geographic areas with associated topographic and climatic diversity, the variable malaria epidemiology in India is associated with high parasite genetic diversity and rapidly evolving drug resistance, differential distribution of vector species and emerging insecticide resistance and underlying human genetic diversity and past evolutionary histories. Further, changing climatic patterns have possibly changed malaria epidemiology to a great extent. The outcome of these changes is an increased incidence of Plasmodium falciparum over the P. vivax malaria in recent years. Accordingly, the drug and insecticide application policy in India has changed too. The above facts and associated rapid shifting trend of malaria epidemiology makes India a hot-spot for malaria research.

Tropical Anemia: One of Africa's Great Killers and a Rationale for Linking Malaria and Neglected Tropical Disease Control to Achieve a Common Goal

With more than 1 million child deaths annually, malaria remains the single leading killer of young children in subSaharan Africa [1]. Millions more young children survive, but still suffer from severe anemia and permanent neurological damage [1], as well as more subtle neuropsychiatric disturbances including impaired cognition and memory [2]. Malaria in pregnancy is also a major cause of maternal deaths and low birth weight [3], and together these maternal and child health effects account for huge economic losses that trap families in poverty [4]. As a result, malaria is now considered one of the key forces preventing the development of the African continent [4]. In response to a growing malaria crisis, the Bill & Melinda Gates Foundation recently announced an ambitious program of expanded malaria control, with a long-term goal of malaria eradication [5]. The major elements of expanded malaria control include strengthening of prevention and treatment programs worldwide through the Global Fund to Fight AIDS, Tuberculosis and Malaria, the United States President’s Malaria Initiative, the World Bank Malaria Control Booster Program, scale-up of national control programs [5], coordination through the Roll Back Malaria Partnership based at the World Health Organization (WHO) [6], and advocacy by Malaria No More and other organizations [7]. In the early 1970s, an intensified effort to interrupt the transmission of malaria was conducted in a group of villages near the town of Garki in northern Nigeria [8]. Through household spraying, mass drug administration, and other measures, there was a temporary reduction in malaria deaths, but overall the Garki Project showed that interrupting malaria transmission was not possible even when a full armamentarium of control tools was applied [8]. An important difference between then and now is the availability of long-lasting insecticide-treated nets (LLITNs) and artemisinin combination therapy (ACT)-based treatments, in addition to the increased willingness to deploy indoor insecticide spraying [1]. However, it is unclear whether even the deployment of these new control tools will directly lead to total success in malaria control because of the threat of emerging insecticide resistance to pyrethroids and the potential for emergence of artemisinin resistance [1,9,10]. Also, parallel efforts will be required to strengthen Africa’s weakened health systems [11,12], which today suffer from widespread malaria misdiagnoses in endemic areas [13] and a lack of access to essential medicines and LLITNs [14]. Accordingly, WHO and other organizations are embarking on renewed efforts to strengthen health systems in Africa and elsewhere [15], while product development partnerships have evolved in a concerted push to accelerate the development of additional new malaria drugs and insecticides, and safe and effective antimalaria vaccines [1,5,16]. There is yet another promising, low-cost and highly cost-effective, and complementary approach for potentially reducing the morbidity of malaria in sub-Saharan Africa, which builds on existing efforts and could be implemented for as little as US$0.50 per person per year or less than 10% add-on to projected malaria control costs [17–20]. In sub-Saharan Africa, where more than 90% of malaria deaths occur, children and pregnant women are simultaneously infected with both malaria and a group of other parasitic diseases, known as the neglected tropical diseases (NTDs). The major NTDs in sub-Saharan Africa include hookworm infection (198 million cases) and other soil-transmitted helminth infections such as ascariasis and trichuriasis (173 million and 162 million cases, respectively), schistosomiasis (166 million), trachoma (33 million), lymphatic filariasis (46 million), and onchocerciasis (18–37 million) [17,18]. There is evidence that some of these NTDs exert an adverse influence on the clinical outcome of malaria in childhood and in pregnancy [21–24], and even possibly on malaria transmission [25]. Shown in Figure 1 is a previously published map demonstrating the geographic overlap and co-endemicity of falciparum malaria and