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1.
Nat Commun ; 12(1): 2553, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33953207

RESUMO

Pyrethrum extracts from flower heads of Chrysanthemum spp. have been used worldwide in insecticides and repellents. While the molecular mechanisms of its insecticidal action are known, the molecular basis of pyrethrum repellency remains a mystery. In this study, we find that the principal components of pyrethrum, pyrethrins, and a minor component, (E)-ß-farnesene (EBF), each activate a specific type of olfactory receptor neurons in Aedes aegypti mosquitoes. We identify Ae. aegypti odorant receptor 31 (AaOr31) as a cognate Or for EBF and find that Or31-mediated repellency is significantly synergized by pyrethrin-induced activation of voltage-gated sodium channels. Thus, pyrethrum exerts spatial repellency through a novel, dual-target mechanism. Elucidation of this two-target mechanism may have potential implications in the design and development of a new generation of synthetic repellents against major mosquito vectors of infectious diseases.


Assuntos
Chrysanthemum cinerariifolium/metabolismo , Culicidae/efeitos dos fármacos , Repelentes de Insetos/farmacologia , Inseticidas/farmacologia , Piretrinas/farmacologia , Aedes/efeitos dos fármacos , Animais , Chrysanthemum cinerariifolium/genética , Técnicas de Inativação de Genes , Controle de Mosquitos , Mosquitos Vetores , Neurônios , Receptores Odorantes/genética , Canais de Sódio Disparados por Voltagem
2.
Molecules ; 26(8)2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33923456

RESUMO

In this study, Magnolia citrata Noot and Chalermglin (Magnoliaceae) essential oil (MCEO) was evaluated for insecticidal activity against the yellow fever mosquito Aedes aegypti and attractant activity for the Mediterranean fruit fly Ceratitis capitata. The leaves of Magnolia citrata (Gioi chanh) were collected from northwestern Vietnam, and the water-distilled MCEO was analyzed by gas-chromatography and mass spectrometry (GC-MS). The major constituents of MCEO were identified as linalool 19%, geranial 16%, citronellal 14%, neral 14%, and sabinene 12%. MCEO showed 100% mortality at 1 µg/µL against 1st instar larvae of Ae. aegypti (Orlando strain, ORL), and the oil exhibited 54% (ORL) and 68% (Puerto Rico strain) mortality at 5 µg/mosquito against Ae. aegypti adult females. Initial screens showed that MCEO had weak insecticidal activity compared to the positive control permethrin. In bioassays with sterile male C. capitata, MCEO exhibited moderately strong attraction, comparable to that observed with a positive control, Tetradenia riparia essential oil (TREO). Herein, the insecticidal and attractant activities of MCEO are reported for the first time.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Inseticidas/farmacologia , Magnolia/química , Aedes/efeitos dos fármacos , Animais , Ceratitis capitata/efeitos dos fármacos , Magnoliaceae/química , Óleos Voláteis/farmacologia
3.
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
4.
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
5.
Molecules ; 26(4)2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33572261

RESUMO

Chromatographic purification of the alcoholic extract from the aerial parts of the Saudi plant Nuxia oppositifolia (Hochst.), Benth., resulted in five isolated phenolic compounds. Two flavones, hispidulin (1) and jaceosidin (2), and the phenylethanoid glycosides, verbascoside (3), isoverbascoside (4), and conandroside (5), were identified and their chemical structures were determined by spectroscopic analyses. The insecticidal activity of compounds 1 and 2, in addition to 11 compounds isolated in a previous research (6-16), was evaluated against the Yellow Fever mosquito, Aedes aegypti. Four compounds displayed adulticidal activity with LD50 values of 2-2.3 µg/mosquito. Free radical scavenging properties of the plant extracts and compounds (1-5) were evaluated by measuring the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonate radical cation (ABTS•+) scavenging activity. All compounds exhibited notable activity, compared with the positive control, l-Ascorbic acid. This study suggests that N. oppositifolia could be a promising source of secondary metabolites, some with lethal adulticidal effect against Ae. aegypti.


Assuntos
Aedes/crescimento & desenvolvimento , Antioxidantes/farmacologia , Sequestradores de Radicais Livres/farmacologia , Inseticidas/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Traqueófitas/química , Aedes/efeitos dos fármacos , Animais , Arábia Saudita
6.
PLoS Negl Trop Dis ; 15(2): e0008492, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33591988

RESUMO

Vector control largely relies on neurotoxic chemicals, and insecticide resistance (IR) directly threatens their effectiveness. In some cases, specific alleles cause IR, and knowledge of the genetic diversity and gene flow among mosquito populations is crucial to track their arrival, rise, and spread. Here we evaluated Aedes aegypti populations' susceptibility status, collected in 2016 from six different municipalities of Rio de Janeiro state (RJ), to temephos, pyriproxyfen, malathion, and deltamethrin. We collected eggs of Ae. aegypti in Campos dos Goytacazes (Cgy), Itaperuna (Ipn), Iguaba Grande (Igg), Itaboraí (Ibr), Mangaratiba (Mgr), and Vassouras (Vsr). We followed the World Health Organization (WHO) guidelines and investigated the degree of susceptibility/resistance of mosquitoes to these insecticides. We used the Rockefeller strain as a susceptible positive control. We genotyped the V1016I and F1534C knockdown resistance (kdr) alleles using qPCR TaqMan SNP genotyping assay. Besides, with the use of Ae. aegypti SNP-chip, we performed genomic population analyses by genotyping more than 15,000 biallelic SNPs in mosquitoes from each population. We added previous data from populations from other countries to evaluate the ancestry of RJ populations. All RJ Ae. aegypti populations were susceptible to pyriproxyfen and malathion and highly resistant to deltamethrin. The resistance ratios for temephos was below 3,0 in Cgy, Ibr, and Igg populations, representing the lowest rates since IR monitoring started in this Brazilian region. We found the kdr alleles in high frequencies in all populations, partially justifying the observed resistance to pyrethroid. Population genetics analysis showed that Ae. aegypti revealed potential higher migration among some RJ localities and low genetic structure for most of them. Future population genetic studies, together with IR data in Ae aegypti on a broader scale, can help us predict the gene flow within and among the Brazilian States, allowing us to track the dynamics of arrival and changes in the frequency of IR alleles, and providing critical information to improving vector control program.


Assuntos
Aedes/efeitos dos fármacos , Vetores de Doenças , Resistência a Inseticidas , Inseticidas/farmacologia , Aedes/genética , Aedes/fisiologia , Animais , Bioensaio , Brasil , Perfilação da Expressão Gênica , Técnicas de Genotipagem , Cobaias , Larva/efeitos dos fármacos , Malation/farmacologia , Mutação , Nitrilas/farmacologia , Piretrinas/farmacologia , Piridinas/farmacologia , Temefós/farmacologia
7.
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
8.
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
9.
Viruses ; 13(1)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33466915

RESUMO

Mosquito-borne arthropod-borne viruses (arboviruses) such as the dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) are important human pathogens that are responsible for significant global morbidity and mortality. The recent emergence and re-emergence of mosquito-borne viral diseases (MBVDs) highlight the urgent need for safe and effective vaccines, therapeutics, and vector-control approaches to prevent MBVD outbreaks. In nature, arboviruses circulate between vertebrate hosts and arthropod vectors; therefore, disrupting the virus lifecycle in mosquitoes is a major approach for combating MBVDs. Several strategies were proposed to render mosquitoes that are refractory to arboviral infection, for example, those involving the generation of genetically modified mosquitoes or infection with the symbiotic bacterium Wolbachia. Due to the recent development of high-throughput screening methods, an increasing number of drugs with inhibitory effects on mosquito-borne arboviruses in mammalian cells were identified. These antivirals are useful resources that can impede the circulation of arboviruses between arthropods and humans by either rendering viruses more vulnerable in humans or suppressing viral infection by reducing the expression of host factors in mosquitoes. In this review, we summarize recent advances in small-molecule antiarboviral drugs in mammalian and mosquito cells, and discuss how to use these antivirals to block the transmission of MBVDs.


Assuntos
Aedes/virologia , Antivirais/farmacologia , Infecções por Arbovirus/transmissão , Infecções por Arbovirus/virologia , Arbovírus/efeitos dos fármacos , Mosquitos Vetores/virologia , Aedes/efeitos dos fármacos , Animais , Antivirais/química , Antivirais/uso terapêutico , Infecções por Arbovirus/tratamento farmacológico , Arbovírus/classificação , Células Cultivadas , Descoberta de Drogas/métodos , Avaliação Pré-Clínica de Medicamentos , Humanos , Controle de Mosquitos/métodos , Doenças Transmitidas por Vetores/tratamento farmacológico , Doenças Transmitidas por Vetores/transmissão , Doenças Transmitidas por Vetores/virologia , Replicação Viral/efeitos dos fármacos
10.
J Agric Food Chem ; 69(3): 1091-1106, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33432806

RESUMO

Furanocoumarins are photoactive compounds derived from secondary plant metabolites. They possess many bioactivities, including antioxidative, anticancer, insecticidal, and bactericidal activities. Here, we designed a new scheme for synthesizing 2-arylfuranocoumarin derivatives by condensation, esterification, bromination, and Wittig reaction. We found that 2-thiophenylfuranocoumarin (Iy) had excellent photosensitive activity. Three Iy concentrations (LC25, LC50, and LC75) were used to treat the fourth instar larvae of Aedes aegypti (A. aegypti). The photoactivated toxicity, sublethal dose, mitochondrial dysfunction, oxidative stress level, intestinal barrier dysfunction, and apoptosis were studied. The results showed that Iy induced reactive oxygen species (ROS) production in midgut cells under ultraviolet light. Ultrastructural analysis demonstrated that mitochondria were damaged, and the activities of related enzymes were inhibited. Ultimately, Iy exposure led to excessive ROS production followed by the inhibition of antioxidant enzymes, including SOD, CAT, GPx, and GR, which diminished ROS elimination and escalated oxidative stress in midgut cells, aggravating the degree of oxidative damage in these cells. Histopathological changes were observed in the midgut, which led to intestinal barrier dysfunction. When the elimination of ROS was blocked and it accumulated in cells, apoptosis-related genes, including AeDronc, AeCaspase7, and AeCaspase8, were induced and activated. In addition, Iy affected the growth and development of A. aegypti at sublethal concentrations, and there was an obvious post-lethal effect. Thus, we found that Iy caused midgut damage and apoptosis in A. aegypti larvae under ultraviolet light, which preliminarily revealed the mode of action of Iy in A. aegypti.


Assuntos
Aedes/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Furocumarinas/química , Furocumarinas/toxicidade , Inseticidas/síntese química , Inseticidas/toxicidade , Aedes/fisiologia , Animais , Sistema Digestório/efeitos dos fármacos , Sistema Digestório/metabolismo , Inseticidas/química , Larva/efeitos dos fármacos , Larva/fisiologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo
11.
PLoS Pathog ; 17(1): e1009199, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33465145

RESUMO

The insecticidal Cry11Aa and Cyt1Aa proteins are produced by Bacillus thuringiensis as crystal inclusions. They work synergistically inducing high toxicity against mosquito larvae. It was proposed that these crystal inclusions are rapidly solubilized and activated in the gut lumen, followed by pore formation in midgut cells killing the larvae. In addition, Cyt1Aa functions as a Cry11Aa binding receptor, inducing Cry11Aa oligomerization and membrane insertion. Here, we used fluorescent labeled crystals, protoxins or activated toxins for in vivo localization at nano-scale resolution. We show that after larvae were fed solubilized proteins, these proteins were not accumulated inside the gut and larvae were not killed. In contrast, if larvae were fed soluble non-toxic mutant proteins, these proteins were found inside the gut bound to gut-microvilli. Only feeding with crystal inclusions resulted in high larval mortality, suggesting that they have a role for an optimal intoxication process. At the macroscopic level, Cry11Aa completely degraded the gastric caeca structure and, in the presence of Cyt1Aa, this effect was observed at lower toxin-concentrations and at shorter periods. The labeled Cry11Aa crystal protein, after midgut processing, binds to the gastric caeca and posterior midgut regions, and also to anterior and medium regions where it is internalized in ordered "net like" structures, leading finally to cell break down. During synergism both Cry11Aa and Cyt1Aa toxins showed a dynamic layered array at the surface of apical microvilli, where Cry11Aa is localized in the lower layer closer to the cell cytoplasm, and Cyt1Aa is layered over Cry11Aa. This array depends on the pore formation activity of Cry11Aa, since the non-toxic mutant Cry11Aa-E97A, which is unable to oligomerize, inverted this array. Internalization of Cry11Aa was also observed during synergism. These data indicate that the mechanism of action of Cry11Aa is more complex than previously anticipated, and may involve additional steps besides pore-formation activity.


Assuntos
Aedes/efeitos dos fármacos , Sinergismo Farmacológico , Endotoxinas/metabolismo , Trato Gastrointestinal/efeitos dos fármacos , Proteínas Hemolisinas/metabolismo , Inseticidas/metabolismo , Larva/efeitos dos fármacos , Aedes/metabolismo , Animais , /toxicidade , Proteínas de Bactérias , Endotoxinas/genética , Endotoxinas/toxicidade , Trato Gastrointestinal/metabolismo , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/toxicidade , Inseticidas/toxicidade , Larva/metabolismo , Ligação Proteica
12.
PLoS One ; 16(1): e0244284, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33417600

RESUMO

BACKGROUND: Mosquito-borne diseases remain a significant public health problem in tropical regions. Housing improvements such as screening of doors and windows may be effective in reducing disease transmission, but the impact remains unclear. OBJECTIVES: To examine whether housing interventions were effective in reducing mosquito densities in homes and the impact on the incidence of mosquito-borne diseases. METHODS: In this systematic review and meta-analysis, we searched 16 online databases, including NIH PubMed, CINAHL Complete, LILACS, Ovid MEDLINE, and Cochrane Central Register of Controlled Trials for randomized trials published from database inception to June 30, 2020. The primary outcome was the incidence of any mosquito-borne diseases. Secondary outcomes encompassed entomological indicators of the disease transmission. I2 values were used to explore heterogeneity between studies. A random-effects meta-analysis was used to assess the primary and secondary outcomes, with sub-group analyses for type of interventions on home environment, study settings (rural, urban, or mixed), and overall house type (traditional or modern housing). RESULTS: The literature search yielded 4,869 articles. After screening, 18 studies were included in the qualitative review, of which nine were included in the meta-analysis. The studies enrolled 7,200 households in Africa and South America, reporting on malaria or dengue only. The type of home environmental interventions included modification to ceilings and ribbons to close eaves, screening doors and windows with nets, insecticide-treated wall linings in homes, nettings over gables and eaves openings, mosquito trapping systems, metal-roofed houses with mosquito screening, gable windows and closed eaves, and prototype houses using southeast Asian designs. Pooled analysis depicted a lower risk of mosquito-borne diseases in the housing intervention group (OR = 0.68; 95% CI = 0.48 to 0.95; P = 0.03). Subgroup analysis depicted housing intervention reduced the risk of malaria in all settings (OR = 0.63; 95% CI = 0.39 to 1.01; P = 0.05). In urban environment, housing intervention was found to decrease the risk of both malaria and dengue infections (OR = 0.52; 95% CI = 0.27 to 0.99; P = 0.05).Meta-analysis of pooled odds ratio showed a significant benefit of improved housing in reducing indoor vector densities of both Aedes and Anopheles (OR = 0.35; 95% CI = 0.23 to 0.54; P<0.001). CONCLUSIONS: Housing intervention could reduce transmission of malaria and dengue among people living in the homes. Future research should evaluate the protective effect of specific house features and housing improvements associated with urban development.


Assuntos
Habitação , Malária/prevenção & controle , Controle de Mosquitos/métodos , Doenças Transmitidas por Vetores/prevenção & controle , Aedes/efeitos dos fármacos , Aedes/fisiologia , Animais , Humanos , Inseticidas/farmacologia , Malária/transmissão , Razão de Chances , Fatores de Risco , Doenças Transmitidas por Vetores/transmissão
13.
PLoS One ; 16(1): e0243992, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33428654

RESUMO

Insecticide resistance is a worldwide threat for vector control around the world, and Aedes aegypti, the main vector of several arboviruses, is a particular concern. To better understand the mechanisms of resistance, four isofemale strains originally from French Guiana were isolated and analysed using combined approaches. The activity of detoxification enzymes involved in insecticide resistance was assayed, and mutations located at positions 1016 and 1534 of the sodium voltage-gated channel gene, which have been associated with pyrethroid resistance in Aedes aegypti populations in Latin America, were monitored. Resistance to other insecticide families (organophosphates and carbamates) was evaluated. A large-scale proteomic analysis was performed to identify proteins involved in insecticide resistance. Our results revealed a metabolic resistance and resistance associated with a mutation of the sodium voltage-gated channel gene at position 1016. Metabolic resistance was mediated through an increase of esterase activity in most strains but also through the shifts in the abundance of several cytochrome P450 (CYP450s). Overall, resistance to deltamethrin was linked in the isofemale strains to resistance to other class of insecticides, suggesting that cross- and multiple resistance occur through selection of mechanisms of metabolic resistance. These results give some insights into resistance to deltamethrin and into multiple resistance phenomena in populations of Ae. aegypti.


Assuntos
Aedes/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Proteínas de Insetos/genética , Resistência a Inseticidas/genética , Canais de Sódio Disparados por Voltagem/genética , Aedes/efeitos dos fármacos , Aedes/genética , Animais , Esterases/metabolismo , Feminino , Guiana Francesa , Técnicas de Silenciamento de Genes , Genótipo , Inativação Metabólica/genética , Proteínas de Insetos/antagonistas & inibidores , Proteínas de Insetos/metabolismo , Inseticidas/farmacologia , Mucosa Intestinal/metabolismo , Nitrilas/farmacologia , Oligonucleotídeos/metabolismo , Polimorfismo de Nucleotídeo Único , Proteoma/análise , Proteômica , Piretrinas/farmacologia , Canais de Sódio Disparados por Voltagem/química , Canais de Sódio Disparados por Voltagem/metabolismo
14.
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
15.
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
16.
Acta Trop ; 214: 105789, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33309593

RESUMO

The measures currently used to minimize the spread of arboviruses, comprising dengue, Chikungunya, and Zika virus, involve controlling the size of population of the mosquito Aedes aegypti. However, the search for formulations containing new insecticides is gaining pace due to reports of mosquito populations showing resistance to commonly used compounds. In this study, tablets containing a protein fraction of Moringa oleifera seeds enriched in the WSMoL lectin, known to show larvicidal and ovicidal activities against A. aegypti, were developed. The compatibility between the fraction and the excipients used in obtaining the tablets was evaluated by thermogravimetry (TG), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) absorption spectroscopy. The larvicidal and ovicidal activities of the resulting tablets [5%, 10%, and 15% (w/w) of the fraction] were evaluated, as well as their effect on mosquito oviposition. Assays were also performed using a placebo tablet. According to the TG, DSC, and FTIR results, the protein composition of the fraction did not change when mixed with the components of the formulation. Tablets containing 10% and 15% WSMoL-rich fraction caused mortality of 42.5% and 95% of the larvae after 48 h, respectively, with larvae incubated with these tablets showing reduced acetylcholinesterase activity. All tablets inhibited egg hatching after 72 h (36-74%), and tablets containing 15% fraction were found to exert a repellent effect on oviposition. Our results show that the formulation developed in this study interfered with the life cycle of A. aegypti, and thus show potential for use in the control of this mosquito.


Assuntos
Aedes/efeitos dos fármacos , Inseticidas/farmacologia , Lectinas/farmacologia , Moringa oleifera/química , Extratos Vegetais/farmacologia , Sementes/química , Animais , Feminino , Inseticidas/química , Larva/efeitos dos fármacos , Lectinas/química , Oviposição/efeitos dos fármacos , Extratos Vegetais/química
17.
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
18.
PLoS One ; 15(10): e0228695, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33022007

RESUMO

Aedes aegypti is the main vector of dengue, chikungunya, and Zika viruses, which are of great public health importance in Colombia. Aedes control strategies in Colombia rely heavily on the use of organophosphate and pyrethroid insecticides, providing constant selection pressure and the emergence of resistant populations. In recent years, insecticide use has increased due to the increased incidence of dengue and recent introductions of chikungunya and Zika. In the present study, pyrethroid resistance was studied across six populations of Ae. aegypti from the Caribbean coast of Colombia. Susceptibility to λ-cyhalothrin, deltamethrin, and permethrin was assessed, and resistance intensity was determined. Activity levels of enzymes associated with resistance were measured, and the frequencies of three kdr alleles (V1016I, F1534C, V410L) were calculated. Results showed variations in pyrethroid susceptibility across Ae. aegypti populations and altered enzyme activity levels were detected. The kdr alleles were detected in all populations, with high variations in frequencies: V1016I (frequency ranging from 0.15-0.70), F1534C (range 0.94-1.00), and V410L (range 0.05-0.72). In assays of phenotyped individuals, associations were observed between the presence of V1016I, F1534C, and V410L alleles and resistance to the evaluated pyrethroids, as well as between the VI1016/CC1534/VL410 tri-locus genotype and λ-cyhalothrin and permethrin resistance. The results of the present study contribute to the knowledge of the mechanisms underlying the resistance to key pyrethroids used to control Ae. aegypti along the Caribbean coast of Colombia.


Assuntos
Aedes/genética , Resistência a Inseticidas , Mutação , Piretrinas/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Aedes/efeitos dos fármacos , Animais , Colômbia , Frequência do Gene , Proteínas de Insetos/genética , Masculino , Nitrilas/farmacologia , Permetrina/farmacologia , Fenótipo
19.
Pestic Biochem Physiol ; 170: 104686, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32980070

RESUMO

New insecticides are urgently needed for the control of arthropod vectors of public health diseases. As resistance to many insecticides used for the control of public health pests is ubiquitous, all available chemistries should be evaluated for their potential to effectively control both insecticide-susceptible and insecticide-resistant strains of mosquitoes. This study aimed to evaluate p-p'-difluoro-diphenyl-trichloroethane (DFDT) as a mosquito control technology and relate its activity to that of DDT. We found that topical DFDT was significantly less toxic than DDT to both pyrethroid-susceptible and pyrethroid-resistant strains of Anopheles gambiae and Aedes aegypti. Direct nervous system recording from Drosophila melanogaster CNS demonstrated that DFDT is approximately 10-times less potent than DDT at blocking nerve firing, which may explain its relatively lower toxicity. DFDT was shown to be at least 4500 times more vapor-active than DDT, with an LC50 in a vapor toxicity screening assay of 2.2 µg/cm2. Resistance to DFDT was assessed in two mosquito strains that possess target-site mutations in the voltage-gated sodium channel and upregulated metabolic activity. Resistance ratios for Akdr (An. gambiae) and Puerto Rico (Ae. aegypti) strains were 9.2 and 12.2, respectively. Overall, this study demonstrates that DFDT is unlikely to be a viable public health vector control insecticide.


Assuntos
Aedes/efeitos dos fármacos , Inseticidas/farmacologia , Inseticidas/toxicidade , Piretrinas/toxicidade , Animais , Compostos de Bifenilo , DDT/toxicidade , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/genética , Resistência a Inseticidas/efeitos dos fármacos , Mosquitos Vetores , Porto Rico , Tricloroetanos
20.
Pestic Biochem Physiol ; 170: 104666, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32980073

RESUMO

Despite the substantial progress achieved in the characterization of cytochrome P450 (CYP) -based resistance mechanisms in mosquitoes, a number of questions remain unanswered. These include: (i) the regulation and physiology of resistance conferring CYPs; (ii) the actual contribution of CYPs in resistance alone or in combination with other detoxification partners or other resistance mechanisms; (iii) the association between overexpression levels and allelic variation, with the catalytic activity and the intensity of resistance and (iv) the true value of molecular diagnostics targeting CYP markers, for driving decision making in the frame of Insecticide Resistance Management applications. Furthermore, the translation of CYP - based insecticide resistance research in mosquitoes into practical applications, is being developed, but it is not fully exploited, as yet. Examples include the production of high throughput platforms for screening the liability (stability) or inhibition potential of novel insecticidal leads and synergists (add-ons), as well as the exploration of the negative cross resistance concept (i.e. detoxification of certain insecticides, but activation of others pro-insecticides). The goal of this review is to critically summarise the current knowledge and the gaps of the CYP-based metabolic insecticide resistance in Anopheles and Aedes mosquito vectors. The progress and limitations of the protein and the reverse/forward genetic approaches, the understanding and importance of molecular and physiological aspects, as well as the current and future exploitation routes of CYP research are discussed.


Assuntos
Aedes/efeitos dos fármacos , Aedes/genética , Anopheles/efeitos dos fármacos , Anopheles/genética , Inseticidas/farmacologia , Piretrinas , Animais , Sistema Enzimático do Citocromo P-450/genética , Resistência a Inseticidas/efeitos dos fármacos , Resistência a Inseticidas/genética , Mosquitos Vetores/genética
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