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1.
Nat Commun ; 12(1): 2290, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863888

RESUMO

Arthropod-borne viruses pose a major threat to global public health. Thus, innovative strategies for their control and prevention are urgently needed. Here, we exploit the natural capacity of viruses to generate defective viral genomes (DVGs) to their detriment. While DVGs have been described for most viruses, identifying which, if any, can be used as therapeutic agents remains a challenge. We present a combined experimental evolution and computational approach to triage DVG sequence space and pinpoint the fittest deletions, using Zika virus as an arbovirus model. This approach identifies fit DVGs that optimally interfere with wild-type virus infection. We show that the most fit DVGs conserve the open reading frame to maintain the translation of the remaining non-structural proteins, a characteristic that is fundamental across the flavivirus genus. Finally, we demonstrate that the high fitness DVG is antiviral in vivo both in the mammalian host and the mosquito vector, reducing transmission in the latter by up to 90%. Our approach establishes the method to interrogate the DVG fitness landscape, and enables the systematic identification of DVGs that show promise as human therapeutics and vector control strategies to mitigate arbovirus transmission and disease.


Assuntos
Antivirais/administração & dosagem , Vírus Defeituosos/genética , Mosquitos Vetores/efeitos dos fármacos , Infecção por Zika virus/tratamento farmacológico , Zika virus/genética , Aedes/efeitos dos fármacos , Aedes/virologia , Animais , Chlorocebus aethiops , Biologia Computacional , Evolução Molecular Direcionada , Modelos Animais de Doenças , Feminino , Aptidão Genética , Genoma Viral/genética , Células HEK293 , Humanos , Camundongos , Controle de Mosquitos/métodos , Mosquitos Vetores/virologia , Fases de Leitura Aberta/genética , RNA Viral/genética , Células Vero , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia
2.
J Med Entomol ; 58(2): 956-960, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33710312

RESUMO

Aedes aegypti (Linnaeus, 1762) is the insect vector that transmits several deadly human diseases. Although the egg stage is an important phase of its life cycle, the biology of mosquito egg remains poorly understood. Here, we report our investigations on the chemical factors that induced hatching of Ae. aegypti eggs. Commercial yeast extracts were able to increase egg hatching rate in a dose-dependent manner, with a hatching rate that ranged from approximately 10% with 1 g/liter to 80% with 20 g/liter of yeast extract. Notably, the addition of glutathione, a reducing agent that showed no significant effect on egg hatching by itself, enhanced and stabilized the activity of yeast extract for at least 70 h. Because dissolved oxygen in different treatments was maintained at high levels in a narrow range (92-95%), we proposed that yeast extract contains hatching inducing compound (HIC) which is able to trigger egg hatching independent of dissolved oxygen level. The HIC in yeast extract could prove to be a potential starting point to design an effective tool to forcefully induce mosquito eggs to hatch under unfavorable conditions, functioning as a novel method for vector control.


Assuntos
Aedes/crescimento & desenvolvimento , Aedes/efeitos dos fármacos , Animais , Glutationa/farmacologia , Controle de Insetos/métodos , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/crescimento & desenvolvimento , Oviposição/efeitos dos fármacos , Leveduras/metabolismo
3.
Parasite ; 28: 8, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33528357

RESUMO

In Cameroon, pyrethroid-only long-lasting insecticidal nets (LLINs) are still largely used for malaria control. The present study assessed the efficacy of such LLINs against a multiple-resistant population of the major malaria vector, Anopheles coluzzii, in the city of Yaoundé via a cone bioassay and release-recapture experimental hut trial. Susceptibility of field mosquitoes in Yaoundé to pyrethroids, DDT, carbamates and organophosphate insecticides was investigated using World Health Organization (WHO) bioassay tube tests. Mechanisms of insecticide resistance were characterised molecularly. Efficacy of unwashed PermaNet® 2.0 was evaluated against untreated control nets using a resistant colonised strain of An. coluzzii. Mortality, exophily and blood feeding inhibition were estimated. Field collected An. coluzzii displayed high resistance with mortality rates of 3.5% for propoxur (0.1%), 4.16% for DDT (4%), 26.9% for permethrin (0.75%), 50.8% for deltamethrin (0.05%), and 80% for bendiocarb (0.1%). High frequency of the 1014F west-Africa kdr allele was recorded in addition to the overexpression of several detoxification genes, such as Cyp6P3, Cyp6M2, Cyp9K1, Cyp6P4 Cyp6Z1 and GSTe2. A low mortality rate (23.2%) and high blood feeding inhibition rate (65%) were observed when resistant An. coluzzii were exposed to unwashed PermaNet® 2.0 net compared to control untreated net (p < 0.001). Furthermore, low personal protection (52.4%) was observed with the resistant strain, indicating reduction of efficacy. The study highlights the loss of efficacy of pyrethroid-only nets against mosquitoes exhibiting high insecticide resistance and suggests a switch to new generation bed nets to improve control of malaria vector populations in Yaoundé.


Assuntos
Anopheles , Resistência a Inseticidas , Mosquiteiros Tratados com Inseticida , Controle de Mosquitos , Mosquitos Vetores , Piretrinas , África Ocidental , Animais , Anopheles/efeitos dos fármacos , Anopheles/genética , Camarões , Mosquiteiros Tratados com Inseticida/normas , Inseticidas/farmacologia , Malária/prevenção & controle , Malária/transmissão , Controle de Mosquitos/normas , Mosquitos Vetores/efeitos dos fármacos , Prevalência , Piretrinas/farmacologia
4.
Mem Inst Oswaldo Cruz ; 115: e200313, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33533870

RESUMO

BACKGROUND: Aedes aegypti is the sole vector of urban arboviruses in French Guiana. Overtime, the species has been responsible for the transmission of viruses during yellow fever, dengue, chikungunya and Zika outbreaks. Decades of vector control have produced resistant populations to deltamethrin, the sole molecule available to control adult mosquitoes in this French Territory. OBJECTIVES: Our surveillance aimed to provide public health authorities with data on insecticide resistance in Ae. aegypti populations and other species of interest in French Guiana. Monitoring resistance to the insecticide used for vector control and to other molecule is a key component to develop an insecticide resistance management plan. METHODS: In 2009, we started to monitor resistance phenotypes to deltamethrin and target-site mechanisms in Ae. aegypti populations across the territory using the WHO impregnated paper test and allelic discrimination assay. FINDINGS: Eight years surveillance revealed well-installed resistance and the dramatic increase of alleles on the sodium voltage-gated gene, known to confer resistance to pyrethroids (PY). In addition, we observed that populations were resistant to malathion (organophosphorous, OP) and alpha-cypermethrin (PY). Some resistance was also detected to molecules from the carbamate family. Finally, those populations somehow recovered susceptibility against fenitrothion (OP). In addition, other species distributed in urban areas revealed to be also resistant to pyrethroids. CONCLUSION: The resistance level can jeopardize the efficiency of chemical adult control in absence of other alternatives and conducts to strongly rely on larval control measures to reduce mosquito burden. Vector control strategies need to evolve to maintain or regain efficacy during epidemics.


Assuntos
Aedes/efeitos dos fármacos , Insetos Vetores/genética , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Mosquitos Vetores/efeitos dos fármacos , Piretrinas/farmacologia , Aedes/genética , Aedes/virologia , Animais , Guiana Francesa , Insetos Vetores/efeitos dos fármacos , Controle de Mosquitos/métodos , Mosquitos Vetores/virologia , Análise Espaço-Temporal
5.
Mol Biol Rep ; 48(1): 41-55, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33454908

RESUMO

Mosquito-transmitted diseases like zika, dengue, chikungunya, and yellow fever are known to affect human health worldwide. Numerous synthetic insecticides have been used as vector control for these diseases, but there is the challenge of environmental toxicity and vector resistance. This study investigated the medicinal and insecticidal potential of Lentinus squarrosulus against Aedes aegypti. The fruiting bodies were identified morphologically as well as using internal transcribed spacer (ITS) sequences for its molecular characterization. Genomic deoxyribonucleic acid (DNA) yield was confirmed with NanoDrop Spectrophotometer ND-1000 and amplified with ITSl and ITS4 primers. The amplicons were sequenced and the National Center for Biotechnology Information (NCBI) database identified the nucleotides. Its ethanol extract was subjected to phytochemical screening and gas chromatography mass spectrometry (GC-MS) analysis and tested against the pupa and fourth instar larva of Aedes aegypti with percentage mortality monitored. The Macrofungus was identified morphologically and confirmed with molecular characterization as Lentinus squarrosulus (LS). The gene sequence was deposited in GenBank (Accession number MK629662.1). GC-MS analysis showed that its ethanol extract has 25 bioactive compounds with 9,12-Octadecadienoic acid, ethyl ester having the highest percentage of 43.32% as well as methyl-2-oxo-1-pyrrolidine acetate and 17-octadecynoic acid having the lowest percentage (0.09%). The macrofungus contained varied concentrations of phytochemicals including phenols (159 mg/g GAE), tannins (1.6 mg/g TAE), and flavonoids (31.4 mg/g QE). The ethanol extract had significant potent effects on Aedes aegypti larva and pupa which could be due to the occurrence and abundance of 9,12-octadecadienoic acid in LS. The LC50 of the extract for larvicidal and pupicidal activities were 2.95 mg/mL and 3.55 mg/mL, respectively, while its LC90 were 6.31 mg/mL and 5.75 mg/mL respectively. Lentinus squarrosulus had insecticidal effects against the Aedes aegypti larva and pupa and possessed great potential as a source of alternative medicine and eco-friendly insecticides.


Assuntos
Aedes/efeitos dos fármacos , Lentinula/química , Extratos Vegetais/farmacologia , Viroses/prevenção & controle , Aedes/patogenicidade , Animais , Etanol/química , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Inseticidas/química , Inseticidas/farmacologia , Larva/efeitos dos fármacos , Larva/patogenicidade , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/patogenicidade , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Viroses/epidemiologia
6.
Acta Trop ; 216: 105820, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33400915

RESUMO

Malaria vector control in Mali relies heavily on the use of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) in selected districts. As part of strengthening vector control strategies in Koulikoro district, the National Malaria Control Programme (NMCP) through the support from the US President's Malaria Initiative (PMI) has strategically driven the implementation of IRS, with the LLINs coverage also rising from 93.3% and 98.2%. Due to the increased reports of vector resistance to both pyrethroid and carbamates, there was a campaign for the use of pirimiphos-methyl, an organophosphate at Koulikoro between 2015 and 2016. In this study, the effect of IRS on malaria transmission was assessed, by comparing some key entomological indices between Koulikoro, where IRS was implemented and its neighboring district, Banamba that has never received IRS as vector control intervention. The study was conducted in two villages of each district (Koulikoro and Banamba). Pyrethrum spray catches and entry window trapping were used to collect mosquitoes on a monthly basis. WHO tube tests were carried out to assess mosquito susceptibility to insecticides. Mosquitoes were identified to species level by PCR and their infection to P. falciparum was detected by Enzyme Linked-Immuno-Sorbent Assay (ELISA). Of the 527 specimens identified, An. coluzzii was the most frequent species (95%) followed by An. gambiae (4%) and An. arabiensis (1%). Its density was rainfall dependent in the no-IRS area, and almost independent in the IRS area. The infection rate (IR) in the no-IRS area was 0.96%, while it was null in the IRS area. In the no-IRS area, the entomological inoculation rate (EIR) was 0.21 infective bites /person month with a peak in September. High resistance to pyrethroids and carbamates and susceptibility to organophosphates was observed at all sites. The introduction of pirimiphos-methyl based IRS for vector control resulted in a significant decrease in malaria transmission. An. gambiae s.l., the main malaria vector in the area, was resistant to pyrethroids and carbamates but remained susceptible to the organophosphate pirimiphos-methyl.


Assuntos
Anopheles/efeitos dos fármacos , Anopheles/parasitologia , Carbamatos/farmacologia , Malária/prevenção & controle , Malária/transmissão , Compostos Organotiofosforados/farmacologia , Piretrinas/farmacologia , Animais , Anopheles/genética , Vetores de Doenças , Feminino , Humanos , Mordeduras e Picadas de Insetos/parasitologia , Resistência a Inseticidas , Inseticidas/farmacologia , Mali , Tipagem Molecular , Controle de Mosquitos/métodos , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/genética , Reação em Cadeia da Polimerase
7.
Parasit Vectors ; 14(1): 9, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407825

RESUMO

BACKGROUND: With widespread insecticide resistance in mosquito vectors, there is a pressing need to evaluate alternatives with different modes of action. Blood containing the antihelminthic drug ivermectin has been shown to have lethal and sub-lethal effects on mosquitoes. Almost all work to date has been on Anopheles spp., but impacts on other anthropophagic vectors could provide new options for their control, or additional value to anti-malarial ivermectin programmes. METHODS: Using dose-response assays, we evaluated the effects of ivermectin delivered by membrane feeding on daily mortality (up to 14 days post-blood feed) and fecundity of an Indian strain of Aedes aegypti. RESULTS: The 7-day lethal concentration of ivermectin required to kill 50% of adult mosquitoes was calculated to be 178.6 ng/ml (95% confidence intervals 142.3-218.4) for Ae. aegypti, which is much higher than that recorded for Anopheles spp. in any previous study. In addition, significant effects on fecundity and egg hatch rates were only recorded at high ivermectin concentrations (≥ 250 ng/ul). CONCLUSION: Our results suggest that levels of ivermectin present in human blood at current dosing regimes in mass drug administration campaigns, or even those in a recent higher-dose anti-malaria trial, are unlikely to have a substantial impact on Ae. aegypti. Moreover, owing to the strong anthropophagy of Ae. aegypti, delivery of higher levels of ivermectin in livestock blood is also unlikely to be an effective option for its control. However, other potential toxic impacts of ivermectin metabolites, accumulation in tissues, sublethal effects on behaviour, or antiviral action might increase the efficacy of ivermectin against Ae. aegypti and the arboviral diseases it transmits, and require further investigation.


Assuntos
Aedes/efeitos dos fármacos , Infecções por Arbovirus/prevenção & controle , Ivermectina/farmacologia , Animais , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/farmacologia , Infecções por Arbovirus/transmissão , Fertilidade/efeitos dos fármacos , Ivermectina/administração & dosagem , Mortalidade , Controle de Mosquitos/métodos , Mosquitos Vetores/efeitos dos fármacos
8.
PLoS Negl Trop Dis ; 15(1): e0009036, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33497375

RESUMO

BACKGROUND: In the absence of vaccines or drugs, insecticides are the mainstay of Aedes-borne disease control. Their utility is challenged by the slow deployment of resources, poor community compliance and inadequate household coverage. Novel application methods are required. METHODOLOGY AND PRINCIPAL FINDINGS: A 10% w/w metofluthrin "emanator" that passively disseminates insecticide from an impregnated net was evaluated in a randomized trial of 200 houses in Mexico. The devices were introduced at a rate of 1 per room and replaced at 3-week intervals. During each of 7 consecutive deployment cycles, indoor resting mosquitoes were sampled using aspirator collections. Assessments of mosquito landing behaviours were made in a subset of houses. Pre-treatment, there were no differences in Aedes aegypti indices between houses recruited to the control and treatment arms. Immediately after metofluthrin deployment, the entomological indices between the trial arms diverged. Averaged across the trial, there were significant reductions in Abundance Rate Ratios for total Ae. aegypti, female abundance and females that contained blood meals (2.5, 2.4 and 2.3-times fewer mosquitoes respectively; P<0.001). Average efficacy was 60.2% for total adults, 58.3% for females, and 57.2% for blood-fed females. The emanators also reduced mosquito landings by 90% from 12.5 to 1.2 per 10-minute sampling period (P<0.05). Homozygous forms of the pyrethroid resistant kdr alleles V410L, V1016L and F1534C were common in the target mosquito population; found in 39%, 24% and 95% of mosquitoes collected during the trial. CONCLUSIONS/SIGNIFICANCE: This is the first randomized control trial to evaluate the entomological impact of any volatile pyrethroid on urban Ae. aegypti. It demonstrates that volatile pyrethroids can have a sustained impact on Ae. aegypti population densities and human-vector contact indoors. These effects occur despite the presence of pyrethroid-resistant alleles in the target population. Formulations like these may have considerable utility for public health vector control responses.


Assuntos
Aedes/efeitos dos fármacos , Ciclopropanos/farmacologia , Fluorbenzenos/farmacologia , Inseticidas/farmacologia , Controle de Mosquitos/métodos , Mosquitos Vetores/efeitos dos fármacos , Aedes/genética , Animais , Comportamento Animal , Dengue/transmissão , Entomologia , Características da Família , Feminino , Humanos , Resistência a Inseticidas/efeitos dos fármacos , Resistência a Inseticidas/genética , México , Mosquitos Vetores/genética , Prevalência , Piretrinas/farmacologia , Projetos de Pesquisa
9.
PLoS One ; 15(12): e0244447, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33373422

RESUMO

Rapidly increasing pyrethroid insecticide resistance and changes in vector biting and resting behavior pose serious challenges in malaria control. Mosquito repellents, especially spatial repellents, have received much attention from industry. We attempted to simulate interactions between mosquitoes and repellents using a machine learning method, the Self-Propelled Particle (SPP) model, which we modified to include attractiveness/repellency effects. We simulated a random walk scenario and scenarios with insecticide susceptible/resistant mosquitoes against repellent alone and against repellent plus attractant (to mimic a human host). Simulation results indicated that without attractant/repellent, mosquitoes would fly anywhere in the cage at random. With attractant, all mosquitoes were attracted to the source of the odor by the end. With repellent, all insecticide-susceptible mosquitoes eventually moved to the corner of the cage farthest from the repellent release point, whereas, a high proportion of highly resistant mosquitoes might reach the attractant release point (the human) earlier in the simulation. At fixed concentration, a high proportion of mosquitoes could be able to reach the host when the relative repellency efficacy (compare to attractant efficacy) was <1, whereas, no mosquitoes reached the host when the relative repellency efficacy was > 1. This result implies that repellent may not be sufficient against highly physiologically insecticide resistant mosquitoes, since very high concentrations of repellent are neither practically feasible nor cost-effective.


Assuntos
Anopheles/fisiologia , Comportamento de Busca por Hospedeiro/efeitos dos fármacos , Repelentes de Insetos/farmacologia , Malária/prevenção & controle , Mosquitos Vetores/fisiologia , Animais , Anopheles/efeitos dos fármacos , Simulação por Computador , Voo Animal/efeitos dos fármacos , Voo Animal/fisiologia , Comportamento de Busca por Hospedeiro/fisiologia , Humanos , Resistência a Inseticidas/fisiologia , Inseticidas/farmacologia , Aprendizado de Máquina , Modelos Biológicos , Controle de Mosquitos/métodos , Mosquitos Vetores/efeitos dos fármacos , Odorantes , Piretrinas/farmacologia
10.
Korean J Parasitol ; 58(5): 543-550, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33202506

RESUMO

Mosquitoes are globally distributed and important vectors for the transmission of many human diseases. Mosquito control is a difficult task and the cost of preventing mosquito-borne diseases is much lower than that for curing the associated diseases. Thus, chemical control remains the most effective tool for mosquito. Due to the long-term intensive use of insecticides to control mosquito vectors, resistance to most chemical insecticides has been reported. This study aimed to investigate the relationship between insecticide resistance and target site mutation of L1014 kdr and G119 ace alleles in 5 species/species group of mosquitoes (Aedes vexans, Ae. albopictus, Anopheles spp., Culex pipiens complex, and Cx. tritaeniorhynchus) obtained from 6 collection sites. For Anopheles spp., the proportion of mosquitoes with mutated alleles in L1014 was 88.4%, homozygous resistant genotypes were observed in 46.7%, and heterozygous resistant genotypes were observed in 41.8%. For the Cx. pipiens complex and Cx. tritaeniorhynchus species, homozygous resistant genotypes were found in 25.9% and 9.8%, respectively. However, target site mutation of L1014 in the Ae. vexans nipponii and Ae. albopictus species was not observed. Anopheles spp., Cx. pipiens complex, and Cx. tritaeniorhynchus mosquitoes were resistant to deltamethrin and chlorpyriphos, whereas Ae. vexans nipponii and Ae. albopictus were clearly susceptible. We also found a correlation between the resistance phenotype and the presence of the L1014 kdr and G119 ace mutations only in the Anopheles spp. population. In this study, we suggest that insecticide resistance poses a growing threat and resistance management must be integrated into all mosquito control programs.


Assuntos
Alelos , Proteínas de Insetos/genética , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Controle de Mosquitos , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/genética , Mutação/efeitos dos fármacos , Animais , Monitoramento Ambiental , Humanos , Mosquitos Vetores/classificação , República da Coreia , Doenças Transmitidas por Vetores/prevenção & controle , Doenças Transmitidas por Vetores/transmissão
11.
Mem Inst Oswaldo Cruz ; 115: e200271, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33146241

RESUMO

BACKGROUND: Aedes aegypti is the primary transmitter of several arbovirus with great impact in human health. Controlling vector mosquitoes is an essential and complex task. One promising control method is to use mosquitoes as a vehicle to disseminate tiny particles of juvenile-killing insecticides, such as pyriproxyfen (PPF), to breeding sites. OBJECTIVES: We aimed to investigate the capacity of Ae. aegypti to disseminate two new formulations of PPF in two sites of Rio de Janeiro city for assessment of the efficacy of these products. METHODS: Dissemination stations impregnated with powder and liquid new formulations of PPF were installed in two test sites. Ovitraps were used in the test sites and in a control site for monitoring the presence of Ae. aegypti throughout eggs collection. FINDINGS: Entomological indices indicated that the new formulations of PPF were efficient in reducing eggs abundance. Liquid formulation performed better than powder formulation. Ready-to-use formulations of PPF can be quickly applied in the field and can be replaced after a few months. MAIN CONCLUSIONS: New formulations of PPF associated with mosquito dissemination approach make a valuable vector control strategy, managing to cover places of difficult access for whatever reason. New formulations application requires less labour, being economically attractive.


Assuntos
Aedes/efeitos dos fármacos , Inseticidas/farmacologia , Larva/efeitos dos fármacos , Controle de Mosquitos/métodos , Piridinas/farmacologia , Adolescente , Animais , Cidades , Humanos , Larva/crescimento & desenvolvimento , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/crescimento & desenvolvimento
12.
SAR QSAR Environ Res ; 31(10): 717-739, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32930630

RESUMO

Aedes aegypti is the primary vector of several infectious viruses that cause yellow, dengue, chikungunya, and Zika fevers. Recently, plant-derived products have been tested as safe and eco-friendly larvicides against Ae. aegypti. The present study aimed to improve QSAR models for 62 larvicidal phytocompounds against Ae. aegypti via the Monte Carlo method based on the index of the ideality of correlation (IIC) criterion. The representation of structures was done with SMILES. Three splits were prepared randomly and three QSAR models were constructed using IIC target function. The molecular descriptors were selected from SMILES descriptors and the hydrogen-filled molecular graphs. The predictability of three models was evaluated on the validation sets, the r 2 of which was 0.9770, 0.8660, and 0.8565 for models 1 to 3, respectively. The statistical results of three randomized splits indicated that robust, simple, predictive, and reliable models were obtained for different sets. From the modelling results, important descriptors were identified to enhance and reduce the larvicidal activity of compounds. Based on the identified important descriptors, some new structures of larvicidal compounds were proposed. The larvicidal activity of novel molecules designed further was supported by docking studies. Using the simple QSAR model, one can predict pLC50 of new similarity larvicidal phytocompounds.


Assuntos
Aedes/efeitos dos fármacos , Inseticidas/farmacologia , Mosquitos Vetores/efeitos dos fármacos , Relação Quantitativa Estrutura-Atividade , Aedes/crescimento & desenvolvimento , Animais , Inseticidas/química , Larva/efeitos dos fármacos , Mosquitos Vetores/crescimento & desenvolvimento
13.
PLoS Negl Trop Dis ; 14(9): e0008576, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32881865

RESUMO

BACKGROUND: The ability of cluster-randomized trials to capture mass or indirect effects is one reason for their increasing use to test interventions against vector-borne diseases such as malaria and dengue. For the same reason, however, the independence of clusters may be compromised if the distances between clusters is too small to ensure independence. In other words they may be subject to spillover effects. METHODS: We distinguish two types of spatial spillover effect: between-cluster dependence in outcomes, or spillover dependence; and modification of the intervention effect according to distance to the intervention arm, or spillover indirect effect. We estimate these effects in trial of insecticide-treated materials against the dengue mosquito vector, Aedes aegypti, in Venezuela, the endpoint being the Breteau index. We use a novel random effects Poisson spatial regression model. Spillover dependence is incorporated via an orthogonalized intrinsic conditional autoregression (ICAR) model. Spillover indirect effects are incorporated via the number of locations within a certain radius, set at 200m, that are in the intervention arm. RESULTS: From the model with ICAR spatial dependence, and the degree of surroundedness, the intervention effect is estimated as 0.74-favouring the intervention-with a 95% credible interval of 0.34 to 1.69. The point estimates are stronger with increasing surroundedness within intervention locations. CONCLUSION: In this trial there is some evidence of a spillover indirect effect of the intervention, with the Breteau index tending to be lower in locations which are more surrounded by locations in the intervention arm.


Assuntos
Aedes/efeitos dos fármacos , Inseticidas/farmacologia , Controle de Mosquitos/métodos , Mosquitos Vetores/efeitos dos fármacos , Aedes/fisiologia , Animais , Dengue/transmissão , Humanos , Mosquitos Vetores/fisiologia , Análise Espacial , Venezuela
14.
PLoS One ; 15(9): e0230984, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32946446

RESUMO

Insecticide resistance genes are often associated with pleiotropic effects on various mosquito life-history traits. However, very little information is available on the impact of insecticide resistance on blood feeding process in mosquitoes. Here, using two recently detected DNA-based metabolic markers in the major malaria vector, An. funestus, we investigated how metabolic resistance genes could affect the blood meal intake. After allowing both the field F1 and lab F8 Anopheles funestus strains to feed on the human arm for 30 minutes, we assessed the association between key parameters of blood meal process including, probing time, feeding duration, blood feeding success, blood meal size, and markers of glutathione S-transferase (L119F-GSTe2) and cytochrome P450 (CYP6P9a_R)-mediated metabolic resistance. None of the parameters of blood meal process was associated with L119F-GSTe2 genotypes. By contrast, for CYP6P9a_R, homozygous resistant mosquitoes were significantly more able to blood-feed than homozygous susceptible (OR = 3.3; CI 95%: 1.4-7.7; P = 0.01) mosquitoes. Moreover, the volume of blood meal ingested by CYP6P9a-SS mosquitoes was lower than that of CYP6P9a-RS (P<0.004) and of CYP6P9a-RR (P<0.006). This suggests that CYP6P9a gene is inked with the feeding success and blood meal size of An. funestus. However, no correlation was found in the expression of CYP6P9a and that of genes encoding for salivary proteins involved in blood meal process. This study suggests that P450-based metabolic resistance may influence the blood feeding process of Anopheles funestus mosquito and consequently its ability to transmit malaria parasites.


Assuntos
Anopheles/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Glutationa Transferase/metabolismo , Proteínas de Insetos/metabolismo , Mosquitos Vetores/metabolismo , Animais , Anopheles/efeitos dos fármacos , Anopheles/genética , Anopheles/parasitologia , Sangue/metabolismo , Camarões , Sistema Enzimático do Citocromo P-450/genética , Comportamento Alimentar , Feminino , Glutationa Transferase/genética , Humanos , Proteínas de Insetos/genética , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Malária/parasitologia , Malária/prevenção & controle , Malária/transmissão , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/genética , Mosquitos Vetores/parasitologia , Plasmodium/patogenicidade , Piretrinas/farmacologia , Proteínas e Peptídeos Salivares/metabolismo
15.
PLoS Med ; 17(9): e1003248, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32946451

RESUMO

BACKGROUND: Two billion long-lasting insecticidal nets (LLINs) have been procured for malaria control. A functional LLIN is one that is present, is in good physical condition, and remains insecticidal, thereby providing protection against vector-borne diseases through preventing bites and killing disease vectors. The World Health Organization (WHO) prequalifies LLINs that remain adequately insecticidal 3 years after deployment. Therefore, institutional buyers often assume that prequalified LLINs are functionally identical with a 3-year lifespan. We measured the lifespans of 3 LLIN products, and calculated their cost per year of functional life, to demonstrate the economic and public health importance of procuring the most cost-effective LLIN product based on its lifespan. METHODS AND FINDINGS: A randomised double-blinded trial of 3 pyrethroid LLIN products (10,571 nets in total) was conducted at 3 follow-up points: 10 months (August-October 2014), 22 months (August-October 2015), and 36 months (October-December 2016) among 3,393 households in Tanzania using WHO-recommended methods. Primary outcome was LLIN functional survival (LLIN present and in serviceable condition). Secondary outcomes were (1) bioefficacy and chemical content (residual insecticidal activity) and (2) protective efficacy for volunteers sleeping under the LLINs (bite reduction and mosquitoes killed). Median LLIN functional survival was significantly different between the 3 net products (p = 0.001): 2.0 years (95% CI 1.7-2.3) for Olyset, 2.5 years (95% CI 2.2-2.8) for PermaNet 2.0 (hazard ratio [HR] 0.73 [95% CI 0.64-0.85], p = 0.001), and 2.6 years (95% CI 2.3-2.8) for NetProtect (HR = 0.70 [95% CI 0.62-0.77], p < 0.001). Functional survival was affected by accumulation of holes, leading to users discarding nets. Protective efficacy also significantly differed between products as they aged. Equivalent annual cost varied between US$1.2 (95% CI $1.1-$1.4) and US$1.5 (95% CI $1.3-$1.7), assuming that each net was priced identically at US$3. The 2 longer-lived nets (PermaNet and NetProtect) were 20% cheaper than the shorter-lived product (Olyset). The trial was limited to only the most widely sold LLINs in Tanzania. Functional survival varies by country, so the single country setting is a limitation. CONCLUSIONS: These results suggest that LLIN functional survival is less than 3 years and differs substantially between products, and these differences strongly influence LLIN value for money. LLIN tendering processes should consider local expectations of cost per year of functional life and not unit price. As new LLIN products come on the market, especially those with new insecticides, it will be imperative to monitor their comparative durability to ensure that the most cost-effective products are procured for malaria control.


Assuntos
Mosquiteiros Tratados com Inseticida/economia , Inseticidas/economia , Controle de Mosquitos/métodos , Animais , Culicidae/efeitos dos fármacos , Vetores de Doenças , Características da Família , Seguimentos , Humanos , Resistência a Inseticidas/efeitos dos fármacos , Mosquiteiros Tratados com Inseticida/tendências , Inseticidas/farmacologia , Malária/prevenção & controle , Controle de Mosquitos/economia , Mosquitos Vetores/efeitos dos fármacos , Piretrinas/farmacologia , Tanzânia/epidemiologia
16.
PLoS Negl Trop Dis ; 14(8): e0008660, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32866199

RESUMO

Aedes mosquitoes can transmit dengue and several other severe vector-borne viral diseases, thereby influencing millions of people worldwide. Insects primarily control and clear the viral infections via their innate immune systems. Mitogen-Activated Protein Kinases (MAPKs) and antimicrobial peptides (AMPs) are both evolutionarily conserved components of the innate immune systems. In this study, we investigated the role of MAPKs in Aedes mosquitoes following DENV infection by using genetic and pharmacological approaches. We demonstrated that knockdown of ERK, but not of JNK or p38, significantly enhances the viral replication in Aedes mosquito cells. The Ras/ERK signaling is activated in both the cells and midguts of Aedes mosquitoes following DENV infection, and thus plays a role in restricting the viral infection, as both genetic and pharmacological activation of the Ras/ERK pathway significantly decreases the viral titers. In contrast, inhibition of the Ras/ERK pathway enhances DENV infection. In addition, we identified a signaling crosstalk between the Ras/ERK pathway and DENV-induced AMPs in which defensin C participates in restricting DENV infection in Aedes mosquitoes. Our results reveal that the Ras/ERK signaling pathway couples AMPs to mediate the resistance of Aedes mosquitoes to DENV infection, which provides a new insight into understanding the crosstalk between MAPKs and AMPs in the innate immunity of mosquito vectors during the viral infection.


Assuntos
Aedes/virologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Vírus da Dengue/imunologia , Quinases de Proteína Quinase Ativadas por Mitógeno/farmacologia , Mosquitos Vetores/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Anti-Infecciosos/farmacologia , Linhagem Celular , Sistema Digestório/virologia , Feminino , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Imunidade Inata , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Mosquitos Vetores/virologia , Carga Viral , Replicação Viral/efeitos dos fármacos
17.
PLoS Comput Biol ; 16(8): e1008136, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32822342

RESUMO

Management strategies for control of vector-borne diseases, for example Zika or dengue, include using larvicide and/or adulticide, either through large-scale application by truck or plane or through door-to-door efforts that require obtaining permission to access private property and spray yards. The efficacy of the latter strategy is highly dependent on the compliance of local residents. Here we develop a model for vector-borne disease transmission between mosquitoes and humans in a neighborhood setting, considering a network of houses connected via nearest-neighbor mosquito movement. We incorporate large-scale application of adulticide via aerial spraying through a uniform increase in vector death rates in all sites, and door-to-door application of larval source reduction and adulticide through a decrease in vector emergence rates and an increase in vector death rates in compliant sites only, where control efficacies are directly connected to real-world experimentally measurable control parameters, application frequencies, and control costs. To develop mechanistic insight into the influence of vector motion and compliance clustering on disease controllability, we determine the basic reproduction number R0 for the system, provide analytic results for the extreme cases of no mosquito movement, infinite hopping rates, and utilize degenerate perturbation theory for the case of slow but non-zero hopping rates. We then determine the application frequencies required for each strategy (alone and combined) in order to reduce R0 to unity, along with the associated costs. Cost-optimal strategies are found to depend strongly on mosquito hopping rates, levels of door-to-door compliance, and spatial clustering of compliant houses, and can include aerial spray alone, door-to-door treatment alone, or a combination of both. The optimization scheme developed here provides a flexible tool for disease management planners which translates modeling results into actionable control advice adaptable to system-specific details.


Assuntos
Surtos de Doenças/prevenção & controle , Inseticidas/farmacologia , Mosquitos Vetores/efeitos dos fármacos , Animais , Humanos
18.
PLoS One ; 15(8): e0237353, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785255

RESUMO

Airborne spatial repellency (SR) is characterized and distinguished from other chemical actions including contact locomotor excitation and toxicity. The use of volatile spatial repellents is a potential new intervention class for combatting mosquito-borne pathogen transmission; therefore, continuing investigations on the actions of these chemicals that modify mosquito host-seeking behavior (i.e., bite prevention) is needed. The objective of this study is to characterize the key behavioral avoidance actions of transfluthrin (TFT) to advance spatial repellent development into practical products. Behavioral avoidance responses were observed for adult laboratory strains of Aedes aegypti, Anopheles minimus and An. dirus, and two field populations of An. harrisoni and Ae. aegypti, respectively. Established TFT sublethal (LC50 and LC75), lethal concentrations (LC99) and discriminating concentrations (DCs) were selected corresponding to each mosquito test species. Spatial repellency and contact excitation ('irritancy') responses on adult mosquitoes to TFT were assessed using an excito-repellency assay system. At LC50, TFT exhibited strong avoidance with An. minimus (60.1% escape) and An. dirus (80% escape) laboratory strains, showing between 12 and 16x greater escape response than Ae. aegypti (5% escape). Repellency responses for field collected Ae. aegypti and An. harrisoni were 54.9 and 47.1% escape, respectively. After adjusting the initial contact escape response (a measure of combined irritancy and repellency) to estimate only escape due to contact, the LC50 and LC99 showed moderate escape irritancy with laboratory Ae. aegypti (41.4% escape) and no contact activity against the field population. Adjustment showed only weak contact activity (16.1% escape) in laboratory An. minimus at LC50. Spatial repellency is the predominant mode of action of TFT among colonized and field mosquitoes used in this study. Established baseline (susceptible) dose-response curves assist in optimizing SR products for mosquito control and pathogen transmission prevention.


Assuntos
Comportamento Animal/efeitos dos fármacos , Ciclopropanos/farmacologia , Fluorbenzenos/farmacologia , Repelentes de Insetos/farmacologia , Mosquitos Vetores/efeitos dos fármacos , Compostos Orgânicos Voláteis/farmacologia , Aedes/efeitos dos fármacos , Aedes/fisiologia , Animais , Anopheles/efeitos dos fármacos , Anopheles/fisiologia , Aprendizagem da Esquiva , Relação Dose-Resposta a Droga , Feminino , Controle de Mosquitos/métodos , Mosquitos Vetores/fisiologia , Doenças Transmitidas por Vetores/prevenção & controle
19.
Proc Natl Acad Sci U S A ; 117(36): 22042-22050, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32843339

RESUMO

Malaria vector control may be compromised by resistance to insecticides in vector populations. Actions to mitigate against resistance rely on surveillance using standard susceptibility tests, but there are large gaps in the monitoring data across Africa. Using a published geostatistical ensemble model, we have generated maps that bridge these gaps and consider the likelihood that resistance exceeds recommended thresholds. Our results show that this model provides more accurate next-year predictions than two simpler approaches. We have used the model to generate district-level maps for the probability that pyrethroid resistance in Anopheles gambiae s.l. exceeds the World Health Organization thresholds for susceptibility and confirmed resistance. In addition, we have mapped the three criteria for the deployment of piperonyl butoxide-treated nets that mitigate against the effects of metabolic resistance to pyrethroids. This includes a critical review of the evidence for presence of cytochrome P450-mediated metabolic resistance mechanisms across Africa. The maps for pyrethroid resistance are available on the IR Mapper website, where they can be viewed alongside the latest survey data.


Assuntos
Anopheles/efeitos dos fármacos , Resistência a Inseticidas , Inseticidas/farmacologia , Malária/transmissão , Controle de Mosquitos/métodos , Mosquitos Vetores/efeitos dos fármacos , África , Animais , Anopheles/fisiologia , Humanos , Mosquiteiros Tratados com Inseticida , Mosquitos Vetores/fisiologia , Piretrinas/farmacologia
20.
Nat Commun ; 11(1): 3646, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32686679

RESUMO

Papua New Guinea (PNG) has the highest malaria transmission outside of Africa. Long-lasting insecticidal nets (LLINs) are believed to have helped to reduce average malaria prevalence in PNG from 16% in 2008 to 1% in 2014. Since 2015 malaria in PNG has resurged significantly. Here, we present observations documenting decreased bioefficacy of unused LLINs with manufacturing dates between 2013 and 2019 collected from villages and LLIN distributors in PNG. Specifically, we show that of n = 167 tested LLINs manufactured after 2013, only 17% are fulfilling the required World Health Organisation bioefficacy standards of ≥ 80% 24 h mortality or ≥ 95% 60 min knockdown in bioassays with pyrethroid susceptible Anopheles farauti mosquitoes. In contrast, all (100%, n = 25) LLINs with manufacturing dates prior to 2013 are meeting these bioefficacy standards. These results suggest that decreased bioefficacy of LLINs is contributing to the malaria resurgence in PNG and increased scrutiny of LLIN quality is warranted.


Assuntos
Malária , Controle de Mosquitos/métodos , Animais , Anopheles/efeitos dos fármacos , Humanos , Mosquiteiros Tratados com Inseticida , Inseticidas/farmacologia , Malária/epidemiologia , Malária/prevenção & controle , Malária/transmissão , Mosquitos Vetores/efeitos dos fármacos , Papua Nova Guiné/epidemiologia , Piretrinas/farmacologia
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