Insecticides represent the most crucial element in the integrated management approach to malaria and other vector-borne diseases. The evolution of insect resistance to long-used substances and the toxicity of organophosphates (OPs) and carbamates are the main factors contributing to the development of new, environmentally safe pesticides. In our work, fourteen compounds of 7-methoxytacrine-tacrine heterodimers were tested for their insecticidal effect. Compounds were evaluated in vitro on insect acetylcholinesterase from Anopheles gambiae (AgAChE) and Musca domestica (MdAChE). The evaluation was executed in parallel with testing on human erythrocyte acetylcholinesterase (HssAChE) and human butyrylcholinesterase (HssBChE) using a modified Ellman's method. Compound efficacy was determined as IC50 values for the respective enzymes and selectivity indexes were expressed to compare the interspecies selectivity. Docking studies were performed to predict the binding modes of selected compounds. K1328 and K1329 provided high HssAChE/AgAChE selectivity outperforming standard pesticides (carbofuran and bendiocarb), and thus can be considered as suitable lead structure for novel anticholinesterase insecticides.

• MeSH
• Acetylcholinesterase metabolism   MeSH
• Anopheles * metabolism   MeSH
• Butyrylcholinesterase MeSH
• Cholinesterase Inhibitors toxicity   MeSH
• Insecticides * MeSH
• Carbamates MeSH
• Carbofuran * MeSH
• Mosquito Vectors MeSH
• Humans MeSH
• Organophosphates MeSH
• Tacrine MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Use of pesticides as a preventive measure is still the most important element in the integrated management approach to malaria and other vector-borne disease parasitoses. In this project, new insecticides with enhanced selectivity to insects and not toxic to mammals and other animal species will be developed. Twenty new acetylcholinesterase (AChE; EC 3.1.1.7) inhibitors, which will covalently bond to the insect specific cysteine, will be prepared. This cysteine is located at the rim of active side in insect and is mutated to phenylalanine in other species. In this project, the synthesis of novel compounds and the structure-biological activity relationship (SAR) evaluation will be performed. Then, selection of the best insecticide candidates and their in vivo safety validation will be carried out and subsequent patent protection before commercialization will be applied.

Používání pesticidů je jako jedno z preventivních opatření stále nejdůležitějším prvkem integrovaného přístupu k léčbě malárie a dalších parazitóz. V rámci tohoto projektu budou vyvinuty nové insekticidy se zvýšenou selektivitou vůči hmyzu, které nebudou toxické pro savce a ostatní živočišné druhy. Bude připraveno 20 nových inhibitorů acetylcholinesterasy (AChE; EC 3.1.1.7), které se budou kovalentně vázat k cysteinu specifickému pro hmyzí enzym. Tento cystein se u hmyzu nachází na okraji aktivního místa a u jiných druhů je mutací zaměněn za fenylalanin. V rámci tohoto projektu bude provedena syntéza nových sloučenin a zhodnocení vztahu mezi strukturou a biologickou aktivitou (SAR). Následně proběhne výběr nejlepších kandidátů, jejich in vivo ověření bezpečnosti s následnou aplikací patentové ochrany včetně potenciálního komerčního využití.

• MeSH
• Acetylcholinesterase drug effects   MeSH
• Anopheles pathogenicity   MeSH
• Butyrylcholinesterase drug effects   MeSH
• Insecticides MeSH
• Humans MeSH
• Malaria prevention & control   MeSH
• Toxicity Tests MeSH
• Environmental Exposure prevention & control   MeSH
• Check Tag
• Humans MeSH

• Conspectus
• Chemikálie
• NML Fields
• cestovní a tropická medicína
• biochemie
• environmentální vědy
• NML Publication type
• závěrečné zprávy o řešení grantu AZV MZ ČR

In Thailand, Anopheles (Cellia) epiroticus Linton et Harbach (Diptera: Culicidae) is the secondary vector of human malaria along coastal regions. While there are some studies of phenotypic variability and population structure of A. epiroticus, more information on morphological variation would enhance epidemiological understanding of medically important mosquito vectors. This research examined morphological variation at three different distances from coastlines of Samut Songkhram Province, Thailand, using landmark-based geometric morphometrics. Wing shape of A. epiroticus was significantly different in the area 0.2 km away from the sea compared to areas 2 and 4 km away from the sea (p < 0.05). Phenotypic variability in wing shape is associated with distance from the sea. Morphological variations in the area closest to the sea were most pronounced, showing a relationship between A. epiroticus and the ecosystem that affects wing geometry. These results provide important information to understand morphological variation of A. epiroticus in coastal areas.

• MeSH
• Anopheles anatomy & histology   MeSH
• Rain MeSH
• Mosquito Vectors anatomy & histology   MeSH
• Wings, Animal anatomy & histology   MeSH
• Malaria MeSH
• Plasmodium MeSH
• Seasons MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Thailand MeSH

Anophelinae mosquitoes are vectors of human malaria, a disease that infects hundreds of millions of people and causes almost 600,000 fatalities annually. Despite their medical importance, laboratory studies on key aspects of Anophelinae reproductive biology have been limited, and in particular, relatively little is known about the role of juvenile hormone (JH) in the control of female reproduction. The study presented here attempts to fill a gap of knowledge in our understanding of the JH control of ovarian development in female Anophelinae mosquitoes, using Anopheles albimanus as a model. Our studies revealed that JH controls the tempo of maturation of primary follicles in An. albimanus in a similar manner to that previously described in Aedes aegypti. At adult eclosion JH hemolymph titer was low, increased in 1-day old sugar-fed insects, and decreased in blood fed individuals. JH titers decreased if An. albimanus females were starved, and were reduced if insects emerged with low teneral reserves, precluding previtellogenic ovarian development. However, absolute hemolymph titers were lower than Ae. aegypti. Decapitation experiments suggested that if teneral reserves are sufficient, factors from the head activate JH synthesis by the corpora allata (CA) during the first 9-12 h after adult emergence. In conclusion, our studies support the hypothesis that JH controls previtellogenic ovarian development in female An. albimanus mosquitoes, in a similar manner that have been described in Culicinae.

• MeSH
• Anopheles drug effects   growth & development   MeSH
• Corpora Allata cytology   drug effects   MeSH
• Hemolymph drug effects   MeSH
• Juvenile Hormones pharmacology   MeSH
• Ovarian Follicle cytology   drug effects   MeSH
• Reproduction MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH

We report the distribution of mosquitoes of the maculipennis complex in two distinct areas of the Czech Republic (Bohemia and South Moravia) and in one locality of neighbouring Slovakia with emphasis on the detection of the newly described cryptic species Anopheles daciae (Linton, Nicolescu & Harbach, 2004). A total of 691 mosquitoes were analysed using a species-specific multiplex PCR assay to differentiate between the members of the maculipennis complex. In the Czech Republic, we found Anopheles maculipennis (with a prevalence rate of 1.4%), Anopheles messeae (49.0%) and Anopheles daciae (49.6%). In Slovakia, only An. messeae (52.1%) and An. daciae (47.9%) were detected. In this study, An. daciae was documented for the first time in the two countries where it represented a markedly higher proportion of maculipennis complex species (with an overall prevalence almost reaching 50%) in comparison to previous reports from Germany, Romania and Poland. The determination of the differential distribution of maculipennis complex species will contribute to assessing risks of mosquito-borne diseases such as malaria or dirofilariasis.

• MeSH
• Anopheles parasitology   MeSH
• Culicidae parasitology   MeSH
• Dirofilariasis epidemiology   parasitology   transmission   MeSH
• Species Specificity MeSH
• Insect Vectors parasitology   MeSH
• Malaria epidemiology   parasitology   transmission   MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Slovakia epidemiology   MeSH

Mosquito-borne diseases (including malaria) belong among the leading causes of death in humans. Vector control is a crucial part of the global strategy for management of mosquito-associated diseases, when insecticide use is the most important component in this effort. However, drug and insecticide resistance threaten the successes made with existing methods. Reduction or elimination of malaria is not possible without effective mosquito control. This article reviews current strategies of intervention in vector control to decrease transmission of disease and covers current relevant knowledge in molecular biology, biochemistry, and medicinal chemistry.

• MeSH
• Acetylcholinesterase chemistry   metabolism   MeSH
• Anopheles parasitology   MeSH
• Insecticides chemistry   pharmacology   MeSH
• Mosquito Vectors drug effects   MeSH
• Humans MeSH
• Malaria parasitology   pathology   MeSH
• Drug Design MeSH
• Insecticide Resistance * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Background: Eliminating falciparum malaria in Cambodia is a top priority, requiring the implementation of novel tools and strategies to interrupt its transmission. To date, few data are available regarding the contributions to malaria transmission of symptomatic and asymptomatic carriers. Methods: Direct-membrane and skin feeding assays (DMFAs, SFAs) were performed, using Anopheles minimus and Anopheles dirus, to determine infectivity of symptomatic falciparum-infected patients and malaria asymptomatic carriers; a subset of the latter were followed up for 2 months to assess their transmission potential. Results: By microscopy and real-time polymerase chain reaction, Plasmodium falciparum gametocyte prevalence rates were, respectively, 19.3% (n = 21/109) and 44% (n = 47/109) on day (D) 0 and 17.9% (n = 5/28) and 89.3% (n = 25/28) in recrudescent patients (Drec) (RT-PCR Drec vs D0 P = .002). Falciparum malaria patient infectivity was low on D0 (6.2%; n = 3/48) and in Drec (8.3%; n = 1/12). Direct-membrane feeding assays and SFAs gave similar results. None of the falciparum (n = 0/19) and 3 of 28 Plasmodium vivax asymptomatic carriers were infectious to mosquitoes, including those that were followed up for 2 months. Overall, P. falciparum gametocytemias were low except in a few symptomatic carriers. Conclusions: Only symptomatic falciparum malaria patients were infectious to mosquito vectors at baseline and recrudescence, highlighting the need to detect promptly and treat effectively P. falciparum patients.

• MeSH
• Anopheles parasitology   MeSH
• Child MeSH
• Adult MeSH
• Mosquito Vectors parasitology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Malaria, Vivax parasitology   transmission   MeSH
• Young Adult MeSH
• Parasites pathogenicity   MeSH
• Plasmodium falciparum pathogenicity   MeSH
• Plasmodium vivax pathogenicity   MeSH
• Prevalence MeSH
• Malaria, Falciparum parasitology   transmission   MeSH
• Animals MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Geographicals
• Cambodia MeSH

BACKGROUND: Despite long-term research on dirofilariosis in Slovakia, little attention has thus far been paid to Dirofilaria vectors. The particular aim of the present study was molecular screening for filarioid parasites in two different habitats of Bratislava, the capital city of Slovakia. In addition, the effect of urbanisation on mosquito species abundance and composition, associated with the risk of mosquito-borne infections, was studied and discussed. METHODS: Mosquitoes were identified by morphological features, and molecular methods were also used for determination of selected individuals belonging to cryptic species from the Anopheles maculipennis and Culex pipiens complexes. The presence of filarioid DNA (Dirofilaria repens, Dirofilaria immitis and Setaria spp.) was detected using standard PCR approaches and sequencing. RESULTS: A total of 6957 female mosquitoes were collected for the study. Overall, the most abundant mosquito species was Aedes vexans, closely followed by unidentified members of the Cx. pipiens complex and the less numerous but still plentiful Ochlerotatus sticticus species. Further investigation of mosquito material revealed 4.26% relative prevalence of Dirofilaria spp., whereby both species, D. repens and D. immitis, were identified. The majority of positive mosquito pools had their origin in a floodplain area on the outskirts of the city, with a relative prevalence of 5.32%; only two mosquito pools (1.26%) were shown to be positive in the residential zone of Bratislava. Setaria spp. DNA was not detected in mosquitoes within this study. CONCLUSIONS: The study presented herein represents initial research focused on molecular mosquito screening for filarioid parasites in urban and urban-fringe habitats of Bratislava, Slovakia. Molecular analyses within the Cx. pipiens complex identified two biotypes: Cx. pipiens biotype pipiens and Cx. pipiens biotype molestus. To our knowledge, Dirofilaria spp. were detected for the first time in Slovakia in mosquitoes other than Ae. vexans, i.e. D. repens in Anopheles messeae and unidentified members of An. maculipennis and Cx. pipiens complexes, and D. immitis in Coquillettidia richiardii and Cx. pipiens biotype pipiens. Both dirofilarial species were found in Och. sticticus. The suitable conditions for the vectors' biology would represent the main risk factor for dirofilariosis transmission.

• MeSH
• Anopheles anatomy & histology   classification   genetics   growth & development   MeSH
• Culex anatomy & histology   classification   genetics   growth & development   MeSH
• Dirofilaria immitis genetics   isolation & purification   MeSH
• Dirofilaria repens genetics   isolation & purification   MeSH
• Dirofilariasis epidemiology   transmission   MeSH
• Risk Assessment MeSH
• Mosquito Vectors anatomy & histology   classification   genetics   growth & development   MeSH
• Population Dynamics * MeSH
• Setaria Nematode genetics   isolation & purification   MeSH
• Setariasis epidemiology   transmission   MeSH
• Urbanization * MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Slovakia epidemiology   MeSH

In Cameroon, many dietary spices are used by traditional healers to cure several diseases such as cancer and microbial infections. Aframomum daniellii, Dichrostachys cinerea and Echinops giganteus are Cameroonian spices widely used as flavourings and as food additives. Moreover, they are traditionally herbal remedies employed to treat several diseases, as well as to control populations of insect pests. In this research, we analysed the chemical composition of A. daniellii, D. cinerea and E. giganteus essential oils and we evaluated their larvicidal potential against larvae of the filariasis and West Nile virus vector Culex quinquefasciatus. The essential oils were obtained from different plant parts by hydrodistillation and their composition was analysed by GC-MS. The three spices exhibited different volatile chemical profiles, being characterized by 1,8-cineole, sabinene and β-pinene (A. daniellii), geraniol and terpinen-4-ol (D. cinerea), and silphiperfol-6-ene and presilphiperfolan-8-ol (E. giganteus). Results showed that the highest larvicidal toxicity on Cx. quinquefasciatus was exerted by D. cinerea essential oil (LC50 = 39.1 μL L(-1)), followed by A. daniellii (pericarp essential oil: LC50 = 65.5 μL L(-1); leaves: LC50 = 65.5μL L(-1); seeds: LC50 = 106.5μL L(-1)) and E. giganteus (LC50 = 227.4 μL L(-1)). Overall, the chance to use the D. cinerea essential oil against Cx. quinquefasciatus young instars seems promising, since it is effective at moderate doses and could be an advantageous alternative to build newer mosquito control tools.

• MeSH
• Anopheles drug effects   growth & development   MeSH
• Culex drug effects   growth & development   MeSH
• Filariasis transmission   MeSH
• Insect Vectors drug effects   growth & development   MeSH
• Insecticides chemistry   pharmacology   MeSH
• Spices analysis   MeSH
• Larva drug effects   growth & development   MeSH
• Plant Leaves chemistry   MeSH
• Mosquito Control methods   MeSH
• Oils, Volatile chemistry   pharmacology   MeSH
• Plant Extracts pharmacology   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Cameroon MeSH

• MeSH
• Aedes * classification   pathogenicity   growth & development   MeSH
• Anopheles pathogenicity   growth & development   MeSH
• Arbovirus Infections prevention & control   transmission   MeSH
• Dengue epidemiology   classification   prevention & control   transmission   MeSH
• Dirofilaria immitis pathogenicity   growth & development   MeSH
• Dirofilariasis MeSH
• Encephalitis, St. Louis prevention & control   transmission   MeSH
• Flavivirus classification   pathogenicity   growth & development   MeSH
• Chikungunya Fever prevention & control   transmission   MeSH
• Encephalitis, Japanese prevention & control   transmission   MeSH
• Humans MeSH
• Malaria prevention & control   transmission   MeSH
• Chikungunya virus pathogenicity   growth & development   MeSH
• La Crosse virus pathogenicity   growth & development   MeSH
• West Nile Fever epidemiology   mortality   prevention & control   transmission   MeSH
• Yellow Fever epidemiology   mortality   prevention & control   transmission   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH