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1.
An Acad Bras Cienc ; 92(1): e20180590, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32321017

RESUMO

This study aimed to analyze the possible effects of diflubenzuron on the associated insect fauna under laboratory, semi-field and field conditions. Laboratory bioassays were performed in aquariums with mortality readings (%) every 24h until 96h, and in semi-fields, insects were kept in basins with readings every 24h for up to 12 days, in triplicates and a control. In the field experiment, a collection was performed before the application of diflubenzuron in ten brick factory pits (25m²) and 15 post-application. The values of LC50 and LC90 for Chironomus were 2.77x10-3g/L and 0.86g/L, respectively, and for Buenoa, they were 0.019g/L and 0.92g/L, a strong relationship was observed between mortality and exposure time (r²>0.8) in all concentrations used. In semi-field, similar mean values of emergency inhibition were observed, except for Euthyplociidae, which was more sensitive. There was no significant difference between the data of richness and diversity of aquatic insects in the field experiment, considering an interval of 15 days (p=0.32). Finally, the data suggest that diflubenzuron may have a negative effect on the associated insect fauna, but in the field experiment the environmental conditions of Anopheles breeding sites may have affected its efficiency.


Assuntos
Anopheles/efeitos dos fármacos , Diflubenzuron/farmacologia , Inseticidas/farmacologia , Animais , Larva/efeitos dos fármacos , Dose Letal Mediana , Controle de Mosquitos
2.
Infect Dis Poverty ; 9(1): 30, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32183909

RESUMO

BACKGROUND: As of 2015 thousands of refugees are being hosted in temporary refugee camps in Greece. Displaced populations, travelling and living under poor conditions with limited access to healthcare are at a high risk of exposure to vector borne disease (VBD). This study sought to evaluate the risk for VBD transmission within refugee camps in Greece by analyzing the mosquito and sand fly populations present, in light of designing effective and efficient context specific vector and disease control programs. METHODS: A vector/pathogen surveillance network targeting mosquitoes and sand flies was deployed in four temporary refugee camps in Greece. Sample collections were conducted bi-weekly during June-September 2017 with the use of Centers for Disease Control (CDC) light traps and oviposition traps. Using conventional and molecular diagnostic tools we investigated the mosquito/sand fly species composition, population dynamics, pathogen infection rates, and insecticide resistance status in the major vector species. RESULTS: Important disease vectors including Anopheles sacharovi, Culex pipiens, Aedes albopictus and the Leishmania vectors Phlebotomus neglectus, P. perfiliewi and P. tobbi were recorded in the study refugee camps. No mosquito pathogens (Plasmodium parasites, flaviviruses) were detected in the analysed samples yet high sand fly Leishmania infection rates are reported. Culex pipiens mosquitoes displayed relatively high knock down resistance (kdr) mutation allelic frequencies (ranging from 41.0 to 63.3%) while kdr mutations were also detected in Ae. albopictus populations, but not in Anopheles and sand fly specimens. No diflubenzuron (DFB) mutations were detected in any of the mosquito species analysed. CONCLUSIONS: Important disease vectors and pathogens in vectors (Leishmania spp.) were recorded in the refugee camps indicating a situational risk factor for disease transmission. The Cx. pipiens and Ae. albopictus kdr mutation frequencies recorded pose a potential threat against the effectiveness of pyrethroid insecticides in these settings. In contrast, pyrethroids appear suitable for the control of Anopheles mosquitoes and sand flies and DFB for Cx. pipiens and Ae. albopictus larvicide applications. Targeted actions ensuring adequate living conditions and the establishment of integrated vector-borne disease surveillance programs in refugee settlements are essential for protecting refugee populations against VBDs.


Assuntos
Insetos Vetores/efeitos dos fármacos , Insetos Vetores/genética , Resistência a Inseticidas/genética , Leishmania , Controle de Mosquitos , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/genética , Dinâmica Populacional , Campos de Refugiados , Aedes/efeitos dos fármacos , Aedes/genética , Animais , Anopheles/efeitos dos fármacos , Anopheles/genética , Culex/efeitos dos fármacos , Culex/genética , Feminino , Grécia , Leishmania/genética , Leishmania/patogenicidade , Leishmaniose/epidemiologia , Phlebotomus/efeitos dos fármacos , Phlebotomus/genética , Psychodidae
3.
Rev Soc Bras Med Trop ; 53: e20190018, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32187329

RESUMO

INTRODUCTION: The larvicidal potential of Saussurea costus (Falc.) Lipsch. was studied against the early 4th instar larvae of Anopheles stephensi Liston., Aedes aegypti Linn.,and Culex quinquefasciatus Say. because of the emergence of mosquito resistance to conventional synthetic insecticides. METHODS: At concentrations of 12.5-200 ppm, larvicidal activities were studied under laboratory conditions. RESULTS: After 24 h of exposure, the methanol extract of the roots recorded the highest larvicidal activity against An. stephensi, with LC50 and LC90values of 7.96 and 34.39 ppm, respectively. CONCLUSIONS: We are developing potent larvicidal compound(s) from S. costus for controlling the mosquito larval population.


Assuntos
Aedes/efeitos dos fármacos , Anopheles/efeitos dos fármacos , Culex/efeitos dos fármacos , Inseticidas/farmacologia , Larva/efeitos dos fármacos , Extratos Vegetais/farmacologia , Saussurea/química , Animais , Inseticidas/isolamento & purificação
4.
Parasitol Res ; 119(4): 1201-1208, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32036440

RESUMO

Knowledge of vector species composition and monitoring their change over time is critical to evaluate malaria transmission and assess control interventions. This is especially important in countries such as Botswana, where malaria transmission is subjected to fluctuations due to climate variability. Another important aspect that impacts vector populations is the insecticide resistance. In order to assess species composition and the presence of mutations associated with insecticide resistance, Anopheles specimens from larval samplings and indoor pyrethrum spray sheet collections were analysed. A total of 349 Anopheles were screened by morphology and PCR as belonging to the An. gambiae complex and An. funestus group. Specimens were subsequently analysed for human blood meal and Plasmodium index. Finally, knock-down resistance polymorphisms were assessed. Anopheles arabiensis accounted for the majority of specimens collected through larval (96.7%) and pyrethrum spray sheet collection (87.4%) across all sampling sites, and this species was the only one found positive for human blood and for P. falciparum. Other Anopheles species were collected in small numbers by pyrethrum spray catches, namely An. quadriannulatus, An. longipalpis type C and An. parensis. The authors speculate on changing climate patterns and their possible impact on species composition. The kdr assay revealed that Anopheles mosquitoes were homozygous wild type for both L1014F (kdr-w) and L1014S (kdr-e) mutations. These results highlight the unique vectorial role of An. arabiensis in Botswana and indicated that even with prolonged use of pyrethroids and DDT, the mosquito population has not developed kdr mutations, despite some in vivo evidence of insecticide resistance.


Assuntos
Anopheles/efeitos dos fármacos , Resistência a Inseticidas , Inseticidas/farmacologia , Piretrinas/farmacologia , Animais , Botsuana , Feminino , Humanos , Resistência a Inseticidas/genética , Larva/efeitos dos fármacos , Malária/transmissão , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/genética , Mutação , Reação em Cadeia da Polimerase
5.
PLoS One ; 15(2): e0227811, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32023266

RESUMO

Anopheles darlingi is the main vector of malaria in Brazil, characterized by a high level of anthropophilia and endophagy. Imidacloprid, thiacloprid, and acetamiprid are the most widespread insecticides of the neonicotinoid group. However, they produce adverse effects on the non-target insects. Flupyradifurone has been marketed as an alternative to non-fluorinated neonicotinoids. Neonicotinoids containing trifluoroacethyl substituent reveal increased insecticidal activity due to higher hydrophobicity and metabolic stability. We synthesized novel neonicotinoid insecticides containing fluorinated acceptor groups and their interactions were estimated with the nicotinic acetylcholine receptor (nAChR) binding site by molecular docking studies, to evaluate their larvicidal activity against A. darlingi, and to assess their outdoor photodegradation behavior. New neonicotinoid analogues were prepared and characterized by NMR and mass-spectrometry. The synthesized molecules were modelled by time-dependent density functional theory and analyzed, their interaction with nAChR was investigated by molecular docking. Their insecticide activity was tested on Anopheles larvae collected in suburban area of Manaus, Brazil. Four new fluorinated neonicotinoid analogs were prepared and tested against 3rd instars larvae of A. darlingi showing high larvicidal activity. Docking studies reveal binding modes of the synthesized compounds and suggest that their insecticidal potency is governed by specific interactions with the receptor binding site and enhanced lipophilicity. 2-Chloro-5-(2-trifluoromethyl-pyrrolidin-1-ylmethyl)pyridine 5 showed fast degradation in water maintaining high larvicidal activity. All obtained substances possessed high larvicidal activity in low concentrations in 48 hours of exposure, compared to commercial flupyradifurone. Such activity is connected to a unique binding pattern of the synthesized compounds to insect's nAChR and to their enhanced bioavailability owing to introduction of fluorinated amino-moieties. Therefore, the compounds in question have a high potential for application as control agents for insects transmitting tropical diseases, and they will be less persistent in the environment.


Assuntos
Anopheles/efeitos dos fármacos , Halogenação , Inseticidas/toxicidade , Simulação de Acoplamento Molecular , Neonicotinoides/toxicidade , 4-Butirolactona/análogos & derivados , 4-Butirolactona/química , 4-Butirolactona/toxicidade , Animais , Inseticidas/química , Larva/efeitos dos fármacos , Neonicotinoides/síntese química , Neonicotinoides/química , Piridinas/química , Piridinas/toxicidade , Espectrofotometria Ultravioleta , Eletricidade Estática
6.
Rev Soc Bras Med Trop ; 53: e20190211, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31994661

RESUMO

INTRODUCTION: Anopheles stephensi is the main malaria vector in Southeast Asia. Recently, plant-sourced larvicides are attracting great interests. METHODS: The essential oil was extracted from the leaf of Cinnamomum camphora (L.), and a bioassay was conducted to determine the larvicidal efficacy. The chemical composition of the essential oil was determined by GC-MS analysis. RESULTS: The oil showed strong, dose-dependent larvicidal activities. The onset of larvicidal efficiency was rapid. The LC50 and LC95 were determined as 0.146% and 1.057% at 1 h, 0.031% and 0.237% at 12 h, 0.026% and 0.128% at 24 h, respectively. The oil contains 32 compounds. CONCLUSIONS: The essential oil of C. camphora leaf has an excellent larvicidal potential for the control of A. stephensi.


Assuntos
Anopheles/efeitos dos fármacos , Cinnamomum camphora/química , Inseticidas/farmacologia , Larva/efeitos dos fármacos , Mosquitos Vetores/efeitos dos fármacos , Óleos Voláteis/farmacologia , Animais , Anopheles/classificação , Bioensaio , Inseticidas/isolamento & purificação , Dose Letal Mediana , Mosquitos Vetores/classificação , Óleos Voláteis/isolamento & purificação
7.
Malar J ; 19(1): 9, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906969

RESUMO

BACKGROUND: The complexity of mosquito-borne diseases poses a major challenge to global health efforts to mitigate their impact on people residing in sub-tropical and tropical regions, to travellers and deployed military personnel. To supplement drug- and vaccine-based disease control programmes, other strategies are urgently needed, including the direct control of disease vectors. Modern vector control research generally focuses on identifying novel active ingredients and/or innovative methods to reduce human-mosquito interactions. These efforts include the evaluation of spatial repellents, which are compounds capable of altering mosquito feeding behaviour without direct contact with the chemical source. METHODS: This project examined the impact of airborne transfluthrin from impregnated textile materials on two important malaria vectors, Anopheles dirus and Anopheles minimus. Repellency was measured by movement within taxis cages within a semi-field environment at the National Institute of Hygiene and Epidemiology in Hanoi, Vietnam. Knockdown and mortality were measured in adult mosquito bioassay cages. Metered-volume air samples were collected at a sub-set of points in the mosquito exposure trial. RESULTS: Significant differences in knockdown/mortality were observed along a gradient from the exposure source with higher rates of knockdown/mortality at 2 m and 4 m when compared with the furthest distance (16 m). Knockdown/mortality was also greater at floor level and 1.5 m when compared to 3 m above the floor. Repellency was not significantly different except when comparing 2 m and 16 m taxis cages. Importantly, the two species reacted differently to transfluthrin, with An. minimus being more susceptible to knockdown and mortality. The measured concentrations of airborne transfluthrin ranged from below the limit of detection to 1.32 ng/L, however there were a limited number of evaluable samples complicating interpretation of these results. CONCLUSIONS: This study, measuring repellency, knockdown and mortality in two malaria vectors in Vietnam demonstrates that both species are sensitive to airborne transfluthrin. The differences in magnitude of response between the two species requires further study before use in large-scale vector control programmes to delineate how spatial repellency would impact the development of insecticide resistance and the disruption of biting behaviour.


Assuntos
Anopheles/efeitos dos fármacos , Ciclopropanos/uso terapêutico , Fluorbenzenos/uso terapêutico , Repelentes de Insetos/uso terapêutico , Malária/prevenção & controle , Mosquitos Vetores/efeitos dos fármacos , Animais , Comportamento Alimentar/efeitos dos fármacos , Feminino , Humanos , Resistência a Inseticidas/efeitos dos fármacos , Malária/transmissão , Controle de Mosquitos/métodos , Vietnã
8.
Malar J ; 19(1): 11, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910831

RESUMO

BACKGROUND: Indoor attractive toxic sugar bait (ATSB) has potential as a supplementary vector-control and resistance-management tool, offering an alternative mode of insecticide delivery to current core vector-control interventions, with potential to deliver novel insecticides. Given the high long-lasting insecticidal bed net (LLIN) coverage across Africa, it is crucial that the efficacy of indoor ATSB in combination with LLINs is established before it is considered for wider use in public health. METHODS: An experimental hut trial to evaluate the efficacy of indoor ATSB traps treated with 4% boric acid (BA ATSB) or 1% chlorfenapyr (CFP ATSB) in combination with untreated nets or LLINs (holed or intact), took place at the M'bé field station in central Côte d'Ivoire against pyrethroid resistant Anopheles gambiae sensu lato. RESULTS: The addition of ATSB to LLINs increased the mortality rates of wild pyrethroid-resistant An. gambiae from 19% with LLIN alone to 28% with added BA ATSB and to 39% with added CFP ATSB (p < 0.001). Anopheles gambiae mortality with combined ATSB and untreated net was similar to that of combined ATSB and LLIN regardless of which insecticide was used in the ATSB. The presence of holes in the LLIN did not significantly affect ATSB-induced An. gambiae mortality. Comparative tests against pyrethroid resistant and susceptible strains using oral application of ATSB treated with pyrethroid demonstrated 66% higher survival rate among pyrethroid-resistant mosquitoes. CONCLUSION: Indoor ATSB traps in combination with LLINs enhanced the control of pyrethroid-resistant An. gambiae. However, many host-seeking An. gambiae entering experimental huts with indoor ATSB exited into the verandah trap without sugar feeding when restricted from a host by a LLIN. Although ATSB has potential for making effective use of classes of insecticide otherwise unsuited to vector control, it does not exempt potential selection of resistance via this route.


Assuntos
Anopheles/efeitos dos fármacos , Resistência a Inseticidas/efeitos dos fármacos , Inseticidas/farmacologia , Piretrinas/farmacologia , Açúcares/toxicidade , Animais , Ácidos Bóricos , Costa do Marfim , Culex , Feminino , Humanos , Mosquiteiros Tratados com Inseticida , Masculino , Controle de Mosquitos/métodos , Taxa de Sobrevida
9.
Carbohydr Polym ; 230: 115711, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887890

RESUMO

Cellulose nanocrystal (CNC) and ZnO/CuO nanostructure were successfully synthesized by acid hydrolysis and sol-chemical methods, respectively. For the first time, CNC was used as a host polymer for synthesis of CNC/ZnO/CuO through In-situ solution casting technique. Morphological and structural of CNC, ZnO/CuO and hybrid CNC/ZnO/CuO were investigated by TEM, SEM-EDX, FT-IR, XRD and XPS analyses. The analysis revealed that, poly-dispersed, smooth and rod like CNC with an average length of ∼ 85.4 nm, average diameter of ∼13.9 nm and surface charge of 0.01 mmol/gm. As well, irregular shapes as hexagonal, spherical and cluster or star like of ZnO/CuO were formed. EDX and XRD spectra exhibited highly purified CNC/ZnO/CuO and pointed to cellulose II crystallite form with a monoclinic structure. The results demonstrated that, 91.3 % and 99.7 % dye degradation was achieved after 40 min of irradiation due to ZnO/CuO and CNC/ZnO/CuO treatment. Moreover, the inhibition zones formed due to 100 ppm ZnO/CuO were duplicated after integrating CNC (from 7.7:10.3 mm to 14.3:20.3 mm). The hybrid nanostructure exhibit larvicidal activity against Anopheles stephensi better than CNC and ZnO/CuO nanostructures.


Assuntos
Celulose , Cobre , Nanopartículas Metálicas/química , Óxido de Zinco , Animais , Anopheles/efeitos dos fármacos , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Celulose/química , Celulose/farmacologia , Cobre/química , Cobre/farmacologia , Fotólise , Óxido de Zinco/química , Óxido de Zinco/farmacologia
11.
Parasit Vectors ; 13(1): 4, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910892

RESUMO

BACKGROUND: Members of the Anopheles gambiae complex breed in clean, sunlit temporary bodies of water. Anthropogenic pollution is, however, altering the breeding sites of the vectors with numerous biological effects. Although the effects of larval metal pollution have previously been examined, this study aims to assess the transgenerational effects of larval metal pollution on the major malaria vector An. arabiensis. METHODS: Two laboratory strains of An. arabiensis, SENN (insecticide-susceptible) and SENN-DDT (insecticide-resistant), were used in this study. After being bred in water polluted with either cadmium chloride, copper nitrate or lead nitrate, several life history characteristics that can have epidemiological implications (fertility, apoptotic damage to reproductive structures, adult longevity and insecticide tolerance) were examined in the adults and compared to those of adults bred in clean water. RESULTS: All metal treatments reduced fecundity in SENN, but only lead treatment reduced fertility in SENN-DDT. Cadmium chloride exposure resulted in apoptosis and deformation of the testes in both strains. After breeding generation F0 in polluted water, F1 larvae bred in clean water showed an increase in longevity in SENN-DDT adult females. In contrast, after breeding the F0 generation in polluted water, longevity was reduced after cadmium and copper exposure in the F1 generation. Larval metal exposure resulted in an increase in insecticide tolerance in adults of the SENN strain, with SENN-DDT adults gaining the greatest fold increase in insecticide tolerance. CONCLUSIONS: This study demonstrates that a single exposure to metal pollution can have transgenerational effects that are not negated by subsequent breeding in clean water.


Assuntos
Anopheles/crescimento & desenvolvimento , Inseticidas/farmacologia , Larva/efeitos dos fármacos , Metais/farmacologia , Poluentes da Água/farmacologia , Animais , Anopheles/efeitos dos fármacos , Anopheles/fisiologia , Resistência a Medicamentos , Feminino , Fertilidade/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Masculino , Reprodução/efeitos dos fármacos
12.
Ecotoxicol Environ Saf ; 189: 110050, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31816498

RESUMO

This study was aimed to investigate an effectual level of Annona muricata (soursop) extracts on mosquito vectors namely, Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus. The toxicity study on non-target organism and other important biochemical marker enzymes to find and illustrate the exact mechanism of specific enzymes responsible for detoxifying allelochemicals. Among the various soursop seed kernel extracts tested for larvicidal activity, the 0.9% saline extract exhibited maximum mortality (100%) against three vectors at the lowest concentration for 24 h exposure. Based on these findings, the saline extract was opted for further studies including toxicity on non-target organism and systemic effects on important biochemical constituents in the larvae A. aegypti at the lethal threshold time (18 h) with LC50 concentration (0.009 mg/mL). The tested extract against non-target aquatic fourth instar larvae Chironomus costatus was safe up to 0.0028 mg/mL for 24 h exposure and the mortality was observed only above the concentration 0.0028 mg/mL used in the study. The systemic effects on main neuron transmitter Acetylcholinesterase (p ≤ 0.01), xenobiotics detoxifying enzyme of α-and ß-carboxylesterase (p ≤ 0.05; p ≤ 0.01) and antioxidant enzyme glutathione S-transferase (p ≤ 0.05) were reduced significantly in quantitative analysis. Analysis of such biochemical constituents of proteins and enzymes α-and ß-carboxylesterase were considerably down regulated in the resolving native-PAGE. In contrast, acid and alkaline phosphatase were upregulated in both quantitative and qualitative analysis. This investigation clearly demonstrates the soursop extract has potent larvicidal agent with alterations in biochemical constituents of exposed larvae of A. aegypti.


Assuntos
Aedes/efeitos dos fármacos , Annona/química , Inseticidas/farmacologia , Controle de Mosquitos/métodos , Extratos Vegetais/farmacologia , Aedes/enzimologia , Animais , Anopheles/efeitos dos fármacos , Culex/efeitos dos fármacos , Inativação Metabólica , Larva/efeitos dos fármacos , Dose Letal Mediana
13.
Nat Commun ; 10(1): 5634, 2019 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-31822677

RESUMO

The blood-feeding behavior of Anopheles females delivers essential nutrients for egg development and drives parasite transmission between humans. Plasmodium growth is adapted to the vector reproductive cycle, but how changes in the reproductive cycle impact parasite development remains unclear. Here, we show that the bloodmeal-induced miR-276-5p fine-tunes the expression of branched-chain amino acid transferase to terminate the reproductive cycle. Silencing of miR-276 prolongs high rates of amino acid (AA) catabolism and increases female fertility, suggesting that timely termination of AA catabolism restricts mosquito investment into reproduction. Prolongation of AA catabolism in P. falciparum-infected females also compromises the development of the transmissible sporozoite forms. Our results suggest that Plasmodium sporogony exploits the surplus mosquito resources available after reproductive investment and demonstrate the crucial role of the mosquito AA metabolism in within-vector parasite proliferation and malaria transmission.


Assuntos
Anopheles/fisiologia , MicroRNAs/metabolismo , Plasmodium falciparum/crescimento & desenvolvimento , Aminoácidos/metabolismo , Animais , Anopheles/efeitos dos fármacos , Sequência de Bases , Ecdisona/farmacologia , Corpo Adiposo/metabolismo , Feminino , Inativação Gênica , MicroRNAs/genética , Modelos Biológicos , Reprodução/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Esteroides/metabolismo , Transaminases/metabolismo
14.
Proc Natl Acad Sci U S A ; 116(51): 25764-25772, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31801878

RESUMO

Resistance in Anopheles gambiae to members of all 4 major classes (pyrethroids, carbamates, organochlorines, and organophosphates) of public health insecticides limits effective control of malaria transmission in Africa. Increase in expression of detoxifying enzymes has been associated with insecticide resistance, but their direct functional validation in An. gambiae is still lacking. Here, we perform transgenic analysis using the GAL4/UAS system to examine insecticide resistance phenotypes conferred by increased expression of the 3 genes-Cyp6m2, Cyp6p3, and Gste2-most often found up-regulated in resistant An. gambiae We report evidence in An. gambiae that organophosphate and organochlorine resistance is conferred by overexpression of GSTE2 in a broad tissue profile. Pyrethroid and carbamate resistance is bestowed by similar Cyp6p3 overexpression, and Cyp6m2 confers only pyrethroid resistance when overexpressed in the same tissues. Conversely, such Cyp6m2 overexpression increases susceptibility to the organophosphate malathion, presumably due to conversion to the more toxic metabolite, malaoxon. No resistant phenotypes are conferred when either Cyp6 gene overexpression is restricted to the midgut or oenocytes, indicating that neither tissue is involved in insecticide resistance mediated by the candidate P450s examined. Validation of genes conferring resistance provides markers to guide control strategies, and the observed negative cross-resistance due to Cyp6m2 gives credence to proposed dual-insecticide strategies to overcome pyrethroid resistance. These transgenic An. gambiae-resistant lines are being used to test the "resistance-breaking" efficacy of active compounds early in their development.


Assuntos
Anopheles , Genes de Insetos/genética , Genômica/métodos , Resistência a Inseticidas/genética , Mosquitos Vetores , Animais , Animais Geneticamente Modificados , Anopheles/efeitos dos fármacos , Anopheles/genética , Sistema Enzimático do Citocromo P-450/genética , Feminino , Glutationa Transferase/genética , Inseticidas/farmacologia , Malária/prevenção & controle , Malária/transmissão , Masculino , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/genética , Fenótipo
15.
Malar J ; 18(1): 384, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791331

RESUMO

BACKGROUND: Knockdown resistance (kdr) is a well-characterized target-site insecticide resistance mechanism that is associated with DDT and pyrethroid resistance. Even though insecticide resistance to pyrethroids and DDT have been reported in Anopheles albimanus, Anopheles benarrochi sensu lato (s.l.), Anopheles darlingi, Anopheles nuneztovari s.l., and Anopheles pseudopunctipennis s.l. malaria vectors in Latin America, there is a knowledge gap on the role that kdr resistance mechanisms play in this resistance. The aim of this study was to establish the role that kdr mechanisms play in pyrethroid and DDT resistance in the main malaria vectors in Colombia, in addition to previously reported metabolic resistance mechanisms, such as mixed function oxidases (MFO) and nonspecific esterases (NSE) enzyme families. METHODS: Surviving (n = 62) and dead (n = 67) An. nuneztovari s.l., An. darlingi and An. albimanus mosquitoes exposed to diagnostic concentrations of DDT and pyrethroid insecticides were used to amplify and sequence a ~ 225 bp fragment of the voltage-gated sodium channels (VGSC) gene. This fragment spanning codons 1010, 1013 and 1014 at the S6 segment of domain II to identify point mutations, which have been associated with insecticide resistance in different species of Anopheles malaria vectors. RESULTS: No kdr mutations were detected in the coding sequence of this fragment in 129 samples, 62 surviving mosquitoes and 67 dead mosquitoes, of An. darlingi, An. nuneztovari s.l. and An. albimanus. CONCLUSION: Mutations in the VGSC gene, most frequently reported in other species of the genus Anopheles resistant to pyrethroid and DDT, are not associated with the low-intensity resistance detected to these insecticides in some populations of the main malaria vectors in Colombia. These results suggest that metabolic resistance mechanisms previously reported in these populations might be responsible for the resistance observed.


Assuntos
Anopheles/genética , DDT/farmacologia , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Mosquitos Vetores/genética , Piretrinas/farmacologia , Animais , Anopheles/efeitos dos fármacos , Colômbia , Malária , Especificidade da Espécie
16.
Malar J ; 18(1): 407, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31805939

RESUMO

BACKGROUND: Changes in the natural habitats of insect groups are determined the genetic polymorphisms between individuals. The objective of this study was to establish the genetic structure of the Anopheles coluzzii populations in four localities of Benin. METHODS: Insecticide surveys and larval sampling were conducted on 4 study localities, including Cotonou, Ketou, Zagnanado, and Sô-Ava. Molecular characterizations were performed on the Anopheles mosquitoes collected with the allelic and genotypic frequencies of kdr gene determined. The multiple comparison Chi square test for proportions was performed with R version 3.3.3. Next, the observed heterozygosity, expected heterozygosity, and indices of fixation, and genetic differentiation were estimated. Finally, the Hardy-Weinberg equilibrium (EHW) was determined to assess whether panmixia exists in the different populations of mosquitoes of the agroecological zones under study. RESULTS: Carbamates, pyrethroids, organophosphorus and organochlorines use have been reported in all localities except Sô-Ava. Anopheles coluzzii was strongly represented across all study localities. The L1014F allele was observed in the localities of Kétou, Cotonou and Zagnanado. Likewise, insecticide selection pressure of homozygous resistant individuals (L1014F/L1014F) was significantly higher in Kétou, Cotonou and Zagnanado (p value < 0.05). Surprisingly in Sô-Ava, a relatively high frequency of the L1014F allele despite the reported absence of pesticide use was observed. All mosquito populations were found to be deficient in heterozygosity across the study sites (FIS< 0). No genetic differentiation (FST< 0) was observed in the localities of Zagnanado and Kétou. CONCLUSION: The survey on the use of insecticides showed that insecticide selection pressures differ across the investigated localities. It would be desirable to rotate or apply formulations of combined products with different modes of action. Doing so would enable a better management of resistant homozygous individuals, and mitigate the resistance effect of commonly used insecticides.


Assuntos
Anopheles/genética , Variação Genética/efeitos dos fármacos , Genótipo , Inseticidas/farmacologia , Alelos , Animais , Anopheles/efeitos dos fármacos , Anopheles/crescimento & desenvolvimento , Benin , Ecossistema , Larva/efeitos dos fármacos , Larva/genética , Larva/crescimento & desenvolvimento
17.
Infect Dis Poverty ; 8(1): 100, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796068

RESUMO

BACKGROUND: The Sahel region of Chad Republic is a prime candidate for malaria pre-elimination. To facilitate pre-elimination efforts in this region, two populations of Anopheles coluzzii from Central Chad Republic were characterized, their insecticide resistance profile and the possible molecular mechanisms driving the resistance in the field investigated. METHODS: Bloodfed female Anopheles gambiae s.l. resting indoor, were collected at N'djamena and Massakory, Chad in 2018 and characterized for species composition, and infection rate was determined using the TaqMan assay. Susceptibility to various insecticides was assessed using WHO tube bioassays. Cone bioassays were conducted using various long-lasting insecticidal nets (LLINs). Results were analysed using Chi Square test. Knockdown resistance (kdr) and ace-1 markers were investigated by TaqMan genotyping. RESULTS: Anopheles coluzzii was the major vector found in N'djamena (100%) and Massakory (~ 94%). No Plasmodium was found in 147 bloodfed F0 An. coluzzii (82 from N'djamena and 65 from Massakory). High intensity pyrethroid resistance was observed with mortalities of < 2% for permethrin, deltamethrin and etofenprox, and with < 50% and < 60% dead following exposure to 10× diagnostic doses of deltamethrin and permethrin, respectively. For both sites, < 10% mortalities were observed with DDT. Synergist bioassays with piperonylbutoxide significantly recovered pyrethroid susceptibility in Massakory populations, implicating CYP450s (mortality = 13.6% for permethrin, χ2 = 22.8, df = 1, P = 0.0006; mortality = 13.0% for deltamethrin, χ2 = 8.8, df = 1, P < 0.00031). Cone-bioassays established complete loss of efficacy of the pyrethroid-based LLINs; and a 100% recovery of susceptibility following exposure to the roof of PermaNet®3.0, containing piperonylbutoxide. Both populations were susceptible to malathion, but high bendiocarb resistance was observed in Massakory population. The absence of ace-1 mutation points to the role of metabolic resistance in the bendiocarb resistance. Both 1014F and 1014S mutations were found in both populations at around 60% and < 20% respectively. Sequencing of intron-1 of the voltage-gated sodium channel revealed a low genetic diversity suggesting reduced polymorphism. CONCLUSIONS: Multiple resistance in An. coluzzii populations from Chad highlight challenges associated with deployment of LLINs and indoor residual spraying (IRS) in the Sahel of this country. The pyrethroid-synergists LLINs (e.g. PermaNet®3.0) and organophosphate-based IRS maybe the alternatives for malaria control in this region.


Assuntos
Anopheles/fisiologia , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Malária/transmissão , Mosquitos Vetores/fisiologia , Animais , Anopheles/efeitos dos fármacos , Anopheles/genética , Chade , Feminino , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/genética
18.
PLoS One ; 14(12): e0226191, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31869350

RESUMO

BACKGROUND: In view of widespread pyrethroid resistance in malaria vectors in Africa, two long-lasting insecticidal nets (LLINs) incorporated with a synergist, piperonyl butoxide (PBO), DawaPlus 3.0 (deltamethrin + PBO in the roof panel; deltamethrin alone in the side panels) and DawaPlus 4.0 (deltamethrin + PBO in all panels), were evaluated in an experimental hut trial in a rice growing irrigated area in Burkina Faso. Efficacy of nets was tested against free-flying malaria vector, Anopheles gambiae s.l., with high pyrethroid resistance involving L1014F kdr and CYP6P3P450 resistance mechanisms. METHODOLOGY: The efficacy of unwashed and 20-times washed DawaPlus 3.0 (polyethylene roof panel with 120 mg/m2 deltamethrin and 440 mg/m2 PBO; polyester side panels with deltamethrin 100 mg/m2) and DawaPlus 4.0 (same composition as roof of DawaPlus 3.0) was evaluated against DawaPlus 2.0 (80 mg/m2 deltamethrin; positive control). Volunteer sleepers and treatments were rotated in huts using a Latin square design on 63 consecutive nights during August-October 2016. Mortality, human blood-feeding inhibition, deterrence and exit rates of An. gambiae s.l. were monitored. PRINCIPAL FINDINGS: Significantly higher rates of mortality and blood-feeding inhibition were observed with unwashed DawaPlus 4.0 (36%; 47.5%) than unwashed DawaPlus 3.0 (11.8%; 33.3%), DawaPlus 2.0 (4.3%; 6.4%) or untreated net (P < 0.05). Washing reduced personal protective efficacy yet PBO-LLINs were more protective and both met the WHO criteria. CONCLUSIONS: The PBO-containing DawaPlus 4.0 significantly protected against An. gambiae s.l. in the study area. Unwashed DawaPlus 3.0 gave low to moderate protection against the positive control. PBO inhibits oxidase action; hence in areas with active malaria transmission having oxidase mechanisms, PBO nets could confer additional personal protection.


Assuntos
Anopheles/efeitos dos fármacos , Mosquiteiros Tratados com Inseticida , Controle de Mosquitos/métodos , Nitrilos/farmacologia , Butóxido de Piperonila/farmacologia , Piretrinas/farmacologia , Agricultura , Animais , Anopheles/fisiologia , Burkina Faso , Desenho de Equipamento , Voo Animal/efeitos dos fármacos , Gossypium , Humanos , Inseticidas/farmacologia , Malária/prevenção & controle , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/fisiologia , Oryza
19.
Parasit Vectors ; 12(1): 539, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727146

RESUMO

BACKGROUND: Malaria vector control and research rely heavily on monitoring mosquito populations for the development of resistance to public health insecticides. One standard method for determining resistance in adult mosquito populations is the World Health Organization test (WHO bioassay). The WHO bioassay kit consists of several acrylic pieces that are assembled into a unit. Parts of the kit commonly break, reducing the capacity of insectaries to carry out resistance profiling. Since there is at present only a single supplier for the test kits, replacement parts can be hard to procure in a timely fashion. METHODS: Using computer-aided design software and widely available polylactic acid (PLA) filament as a printing material, we 3D designed and printed replacement parts for the WHO bioassay system. We conducted a comparison experiment between original WHO bioassay kits and 3D printed kits to assess congruence between results. The comparison experiment was performed on two Kenyan laboratory strains of Anopheles gambiae (s.s.), Kilifi and Mbita. Student's t-tests were used to assess significant differences between tube types. Finally, we exposed the PLA filament to common solutions used with the bioassay kit. RESULTS: We were able to design and print functional replacements for each piece of the WHO bioassay kit. Replacement parts are functionally identical to and interchangeable with original WHO bioassay parts. We note no significant difference in mortality results obtained from PLA printed tubes and WHO acrylic tubes. Additionally, we observed no degradation of PLA in response to prolonged exposure times of commonly used cleaning solutions. CONCLUSIONS: Our designs can be used to produce replacement parts for the WHO bioassay kit in any facility with a 3D printer, which are becoming increasingly widespread. 3D printing technologies can affordably and rapidly address equipment shortages and be used to develop bespoke equipment in laboratories.


Assuntos
Bioensaio/instrumentação , Resistência a Inseticidas , Mosquitos Vetores/efeitos dos fármacos , Impressão Tridimensional/instrumentação , Design de Software , Animais , Anopheles/efeitos dos fármacos , Bioensaio/métodos , Inseticidas/farmacologia , Malária/prevenção & controle , Malária/transmissão , Organização Mundial da Saúde
20.
Malar J ; 18(1): 357, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703736

RESUMO

BACKGROUND: Insecticide resistance is a growing threat to malaria vector control. Ivermectin, either administered to humans or animals, may represent an alternate strategy to reduce resistant mosquito populations. The aim of this study was to assess the residual or delayed effect of administering a single oral dose of ivermectin to humans on the survival, fecundity and fertility of Anopheles arabiensis in Ethiopia. METHODS: Six male volunteers aged 25-40 years (weight range 64-72 kg) were recruited; four of them received a recommended single oral dose of 12 mg ivermectin and the other two individuals were untreated controls. A fully susceptible insectary colony of An. arabiensis was fed on treated and control participants at 1, 4, 7, 10 and 13 days post ivermectin-administration. Daily mosquito mortality was recorded for 5 days. An. arabiensis fecundity and fertility were measured from day 7 post treatment, by dissection to examine the number of eggs per mosquito, and by observing larval hatching rates, respectively. RESULTS: Ivermectin treatment induced significantly higher An. arabiensis mortality on days 1 and 4, compared to untreated controls (p = 0.02 and p < 0.001, respectively). However, this effect had declined by day 7, with no significant difference in mortality between treated and control groups (p = 0.06). The mean survival time of mosquitoes fed on day 1 was 2.1 days, while those fed on day 4 survived 4.0 days. Mosquitoes fed on the treatment group at day 7 and 10 produced significantly lower numbers of eggs compared to the untreated controls (p < 0.001 and p = 0.04, respectively). An. arabiensis fed on day 7 on treated men also had lower larval hatching rates than mosquitoes fed on days 10 and 13 (p = 0.003 and p = 0.001, respectively). CONCLUSION: A single oral dose of ivermectin given to humans can induce mortality and reduce survivorship of An. arabiensis for 7 days after treatment. Ivermectin also had a delayed effect on fecundity of An. arabiensis that took bloodmeals from treated individuals on day 7 and 10. Additional studies are warranted using wild, insecticide-resistant mosquito populations, to confirm findings and a phase III evaluation among community members in Ethiopia is needed to determine the impact of ivermectin on malaria transmission.


Assuntos
Anopheles/efeitos dos fármacos , Antimaláricos/farmacologia , Ivermectina/farmacologia , Adulto , Animais , Anopheles/fisiologia , Etiópia , Fertilidade/efeitos dos fármacos , Humanos , Longevidade/efeitos dos fármacos , Masculino
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