Altered properties of neuronal sodium channels associated with genetic resistance to pyrethroids.
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Genetic resistance to pyrethroid insecticides involves nervous system insensitivity linked to regulatory and structural genes of voltage-sensitive sodium channels. We examined the properties and relative density of sodium channels in central neurons of susceptible and pyrethroid-resistant (Pyr-R) insects that were homozygous for the amino acid substitution V421M in the I-S6 transmembrane segment. Pyr-R sodium channels show approximately 21-fold lower sensitivity to the synthetic pyrethroid permethrin and a approximately 2-fold increased sensitivity to the alpha-scorpion toxin LqhalphaIT. Pyr-R channels also exhibit altered gating properties, including a approximately 13 mV positive shift in voltage-dependent activation and approximately 7 mV positive shift in steady-state inactivation. Consistent with these changes in gating behavior, Pyr-R central neurons are less excitable, as evidenced by an approximately 11 mV elevation of action potential threshold. No differences in sodium channel density are evident. The altered properties of Pyr-R sodium channels provide a plausible molecular basis for nervous system insensitivity associated with pyrethroid resistance. (+info)
The impact of charging for insecticide on the Gambian National Impregnated Bednet Programme.
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During the second year of the Gambian National Impregnated Bednet Programme (NIBP) charges for insecticide ($0.50 per net) were introduced into the half of the primary health care villages in the country where insecticide have been provided free of charge the previous year. Free insecticide was provided in the remaining villages that had acted as controls during the previous year. In villages where insecticide was provided free, 77% of nets were treated with insecticide. In contrast, in villages where charges were made coverage was only 14%. During the first year of the NIBP, mortality in children was significantly lower in villages where insecticide was provided free than in the control villages. Introduction of a charge for insecticide into the first group of villages and the provision of free insecticide in the latter abolished this difference. The cash income of rural Gambians is very limited and payment of even $2-3 for insecticide treatment for all the bednets in a household represents a substantial outlay. Further education on the benefits of treatment of nets and/or the provision of cheaper insecticide will be required before the full benefits of this powerful new malaria control measure can be fully realised in the Gambia. (+info)
Control of malaria vectors: cost analysis in a province of northern Vietnam.
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The cost of permethrin-treated bednets (50% EC; 0.2 g/m2, 2 rounds per year) was compared to the cost of residual spraying with lambdacyhalothrin 10% WP (0.03 g/m2, once yearly) in Hoa Binh, a mountainous province in northern Vietnam. Calculations of the amounts of insecticides needed were based on national guidelines, on data from a cross-sectional survey and on district activity reports. The actual cost of insecticide required per person per year was lower for impregnation (US$ 0.26) than for spraying (US$ 0.36), but the difference was smaller than expected. The total cost for impregnated bednets per person per year amounted to US$ 0.90 compared to USS 0.47 for spraying. The determining factor was the cost of the net, amounting to US$ 0.58 per person per year, assuming a 5-year life of the net. Other material (excluding nets), labour and transport combined, accounted for only 17% of the impregnation cost and 23% of spraying expenses. However, for the National Malaria Control Programme of Vietnam, the cost per person per year for impregnated bednets amounted to US$ 0.32 only, because the vast majority of nets are bought by the population. For spraying, the programme had to bear the entire cost. (+info)
A new strategy for treating nets. Part 1: formulation and dosage.
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The conventional dosages of pyrethroid insecticides on mosquito nets assume that nets will be retreated at 6-12 month intervals. However, dosage should be related to washing of nets; if nets are only washed once or twice a year, their dosage requirements will be different to those which are washed fortnightly. A 'low-dose, frequent-wash' retreatment system might be technically more appropriate and more affordable where nets are washed frequently, as they are in Dar es Salaam. Moreover, for use as a domestic insecticide, water-based formulations of pyrethroid are preferable to the more commonly used emulsifiable concentrates (ECs). This paper reports laboratory evaluations of three formulations (ECs, Flowable, CS) of three pyrethroids (deltamethrin, lambdacyhalothrin, permethrin). Insecticidal activity was tested using serial bioassays at a range of dosages using Anopheles gambiae. The water-based formulations were no less effective than the ECs, even at the lowest dosages. Nets treated with 3 mg/m2 and then repeatedly washed and retreated after each wash with either 3 mg/m2 or 1 mg/m2 were subjected to gas chromatography analysis. This showed that the amounts of pyrethroid in the nets accumulated rapidly over the first few wash-retreatment cycles and then remained fairly stable over subsequent cycles. These nets gave consistently high bioassay mortalities throughout the experiment, while the mortality declined rapidly after several washes with the nets that were treated at 3 mg/m2 but not retreated. Experimental huts were used to compare the effectiveness of these 2 net retreatment regimes and nets which were not retreated. All nets caused high mortality rates amongst Anopheles females, but had negligible effects on culicines; either in killing them or in preventing feeding. Therefore use of a high 'loading' dose for initial treatment with lower 'maintenance' doses for retreatment may be preferable to ensure that net users promptly perceive the benefits of the insecticide against culicines. (+info)
The effect of delivery mechanisms on the uptake of bed net re-impregnation in Kilifi District, Kenya.
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The results of recently completed trials in Africa of insecticide-treated bed nets (ITBN) offer new possibilities for malaria control. These experimental trials aimed for high ITBN coverage combined with high re-treatment rates. Whilst necessary to understand protective efficacy, the approaches used to deliver the intervention provide few indications of what coverage of net re-treatment would be under operational conditions. Varied delivery and financing strategies have been proposed for the sustainable delivery of ITBNs and re-treatment programmes. Following the completion of a randomized, controlled trial on the Kenyan coast, a series of suitable delivery strategies were used to continue net re-treatment in the area. The trial adopted a bi-annual, house-to-house re-treatment schedule free of charge using research project staff and resulted in over 95% coverage of nets issued to children. During the year following the trial, sentinel dipping stations were situated throughout the community and household members informed of their position and opening times. This free re-treatment service achieved between 61-67% coverage of nets used by children for three years. In 1997 a social marketing approach, that introduced cost-retrieval, was used to deliver the net re-treatment services. The immediate result of this transition was that significantly fewer of the mothers who had used the previous re-treatment services adopted this revised approach and coverage declined to 7%. The future of new delivery services and their financing are discussed in the context of their likely impact upon previously defined protective efficacy and cost-effectiveness estimates. (+info)
Control of zoophilic malaria vectors by applying pyrethroid insecticides to cattle.
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The principal method of malaria control in South and West Asia--indoor residual spraying--is extravagant with insecticide. A more efficient way of deploying insecticide might be to apply it on livestock since the malaria vectors in the region are highly zoophilic. A series of investigations assessed the potential of cattle treated with pyrethroid to control zoophilic mosquitoes. Permethrin, deltamethrin, and lambdacyhalothrin were applied to cattle using a sponge at concentrations of 0.5 g/m2, 0.025 g/m2, and 0.025 g/m2, respectively. 'Whole animal' insecticide bioassays that simulated natural mosquito-host contact were used to measure insecticidal and behavioural effects on wild host-seeking mosquitoes. The bioassays were performed on both sheltered and outdoor grazing animals for up to 45 days post-treatment. The possibility that treatments might cause diversion of host-seeking vectors from cattle to people nearby was also investigated. At the doses tested deltamethrin had the most pronounced and longest-lasting effect, reducing the proportion of bloodfed survivors by over 50% for the first two weeks. The majority of mosquitoes affected by the insecticide were killed before feeding. Insecticidal impact was generally lower on grazing than on sheltered animals. There was no diversion of host-seeking mosquitoes from treated cattle to nearby humans at any stage after treatment. The application of insecticide to livestock using a campaign approach may prove an effective means of controlling malaria in the region. At the doses tested deltamethrin is the most appropriate insecticide for this purpose. (+info)
Insecticide-treated curtains reduce the prevalence and intensity of malaria infection in Burkina Faso.
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A large, randomized controlled trial to investigate the impact of insecticide-treated curtains (ITC) on child mortality was conducted in an area of seasonal, holoendemic malaria in Burkina Faso. 158 communities totalling some 90,000 people were censused and grouped into 16 geographical clusters, 8 of which were randomly selected to receive ITC in June-July 1994, just prior to the rainy season. In September-October 1995, at the peak period of malaria transmission, a cross-sectional survey was conducted in 84 of the villages. A random sample of 905 children aged 6-59 months was identified and visited. 763 children (84%) were present at the time of the visit and recruited into the study. Mothers were asked about fever in the past 24 h, the child's temperature was taken, and a sample of blood collected to identify and quantify malaria infections and to measure haemoglobin (Hb) levels. Children protected by ITC were less likely to be infected with Plasmodium falciparum (risk ratio = 0.92; 95% CI 0.86, 0.98) or P. malariae (risk ratio = 0.42, 95% CI 0.19, 0.95). The mean intensity of P. falciparum infections was lower among children protected by ITC (899 vs. 1583 trophozoites/microliter; P < 0.001), while the mean Hb level was 0.4 g/dl higher (P < 0.001). While we found no evidence that ITC had an impact on the prevalence of malaria-associated fever episodes, the confidence intervals around our estimates of the impact of ITC on malaria morbidity were wide. We conclude that widespread implementation of ITC in this area of high malaria transmission led to a modest reduction in the prevalence of malaria infection and to a more substantial reduction in the intensity of these infections which caused increased Hb levels. We were unable to demonstrate any impact of ITC on malaria morbidity, but the wide confidence intervals around our point estimates do not preclude the possibility of a substantial impact. (+info)
Multiple sites of purinergic control of insulin secretion in mouse pancreatic beta-cells.
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In mouse pancreatic beta-cells, extracellular ATP (0.1 mmol/l) effectively reduced glucose-induced insulin secretion. This inhibitory action resulted from a direct interference with the secretory machinery, and ATP suppressed depolarization-induced exocytosis by 60% as revealed by high-resolution capacitance measurements. Suppression of Ca2+-dependent exocytosis was mediated via binding to P2Y1 purinoceptors but was not associated with inhibition of the voltage-dependent Ca2+ currents or adenylate cyclase activity. Inhibition of exocytosis by ATP resulted from G-protein-dependent activation of the serine/threonine protein phosphatase calcineurin and was abolished by cyclosporin A and deltamethrin. In contrast to the direct inhibitory action on exocytosis, ATP reduced the whole-cell ATP-sensitive K+ (K(ATP)) current by 30% (via activation of cytosolic phospholipase A2), leading to membrane depolarization and stimulation of electrical activity. The stimulatory effect of ATP also involved mobilization of Ca2+ from thapsigargin-sensitive intracellular stores. We propose that the inhibitory action of ATP, by interacting with the secretory machinery at a level downstream to an elevation in [Ca2+]i, is important for autocrine regulation of insulin secretion in mouse beta-cells. (+info)