98 research outputs found

    New Insecticides Promise To Beat Mosquito Resistance In Africa - 12 December 2011

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    MOSHI, TANZANIA - New insecticides to control mosquitoes - being tested in Tanzania - promise to overcome the biggest threat to malaria control in Africa: resistance to pyrethroid insecticides. Dr Richard Oxborough from the London School of Hygiene & Tropical Medicine explained to Sarah Maxwell how his group's research evaluating new insecticides for mosquito nets and spraying inside houses, at the Kilimanjaro Christian Medical Centre in Moshi, Tanzania, is bringing hope for sustainable control of pyrethroid-resistant malaria-transmitting mosquitoes. The development of new insecticides for malaria vector control will help continue the decline of malaria in the region when combined with other malaria-control measures including new drugs, a vaccine and better diagnostic tests

    An integrated response of Trichodesmium erythraeum IMS101 growth and photo-physiology to Iron, CO<sub>2</sub>, and light intensity

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    We have assessed how varying CO2 (180, 380, and 720 μatm) and growth light intensity (40 and 400 μmol photons m-2 s-1) affected Trichodesmium erythraeum IMS101 growth and photophysiology over free iron (Fe') concentrations between 20 and 9,600 pM. We found significant iron dependencies of growth rate and the initial slope and maximal relative PSII electron transport rates (rPm). Under iron-limiting concentrations, high-light increased growth rates and rPm; possibly indicating a lower allocation of resources to iron-containing photosynthetic proteins. Higher CO2 increased growth rates across all iron concentrations, enabled growth to occur at lower Fe' concentrations, increased rPm and lowered the iron half saturation constants for growth (Km). We attribute these CO2 responses to the operation of the CCM and the ATP spent/saved for CO2 uptake and transport at low and high CO2, respectively. It seems reasonable to conclude that T. erythraeum IMS101 can exhibit a high degree of phenotypic plasticity in response to CO2, light intensity and iron-limitation. These results are important given predictions of increased dissolved CO2 and water column stratification (i.e., higher light exposures) over the coming decades.</p

    The trade-off between the light-harvesting and photoprotective functions of fucoxanthin-chlorophyll proteins dominates light acclimation in Emiliania huxleyi (clone CCMP 1516)

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    Mechanistic understanding of the costs and benefits of photoacclimation requires knowledge of how photophysiology is affected by changes in the molecular structure of the chloroplast.We tested the hypothesis that changes in the light dependencies of photosynthesis, nonphotochemical quenching and PSII photoinactivation arises from changes in the abundances of chloroplast proteins in Emiliania huxleyi strain CCMP 1516 grown at 30 (Low Light; LL) and 1000 (High Light; HL) µmol photons m-2 s-1 photon flux densities.Carbon-specific light-saturated gross photosynthesis rates were not significantly different between cells acclimated to LL and HL. Acclimation to LL benefited cells by increasing biomass-specific light absorption and gross photosynthesis rates under low light, whereas acclimation to HL benefited cells by reducing the rate of photoinactivation of PSII under high light. Differences in the relative abundances of proteins assigned to light-harvesting (Lhcf), photoprotection (LI818-like), and the photosystem II (PSII) core complex accompanied differences in photophysiology: specifically, Lhcf:PSII was greater under LL, whereas LI818:PSII was greater in HL.Thus, photoacclimation in E. huxleyi involved a trade-off amongst the characteristics of light absorption and photoprotection, which could be attributed to changes in the abundance and composition of proteins in the light-harvesting antenna of PSII

    Trends in US President’s Malaria Initiative‑funded Indoor Residual Spray Coverage and Insecticide Choice in sub‑Saharan Africa (2008–2015): Urgent Need for Affordable,\ud Long‑Lasting Insecticides

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    This article reports the changing pattern of US President’s Malaria Initiative-funded IRS in sub-Saharan Africa between 2008 and 2015. IRS coverage in sub-Saharan Africa increased from <2 % of the at-risk population in 2005, to 11 % or 78 million people in 2010, mainly as a result of increased funding from PMI. The scaling up of IRS coverage in sub-Saharan Africa has been successful in several epidemiological settings and contributed to reduced malaria transmission rates. However, the spread and intensification of pyrethroid resistance in malaria vectors led many control programmes to spray alternative insecticides. Between 2009 and 2013, pyrethroid spraying decreased from 87 % (13/15) of PMI-funded countries conducting IRS to 44 % (7/16), while bendiocarb use increased from 7 % (1/15) to 56 % (9/16). Long-lasting pirimiphos-methyl CS received WHOPES recommendation in 2013 and was scheduled to be sprayed in 85 % (11/13) of PMI-funded countries conducting IRS in 2015. The gradual replacement of relatively inexpensive pyrethroids, firstly with bendiocarb (carbamate) and subsequently with pirimiphos methyl CS (organophosphate), has contributed to the downscaling of most PMI-funded IRS programmes. Overall, there was a 53 % decrease in the number of structures sprayed between years of peak coverage and 2015, down from 9.04 million to 4.26 million structures. Sizeable reductions in the number of structures sprayed were reported in Madagascar (56 %, 576,320–254,986), Senegal (64 %, 306,916–111,201), Tanzania (68 %, 1,224,095–389,714) and Zambia (63 %, 1,300,000–482,077), while in Angola, Liberia and Malawi PMI-funded spraying was suspended. The most commonly cited reason was increased cost of pesticides, as vector resistance necessitated switching from pyrethroids to organophosphates. There are worrying preliminary reports of malaria resurgence following IRS withdrawal in parts of Benin, Tanzania and Uganda. The increase in malaria cases following the end of the Global Malaria Eradication Programme in 1969 highlights the fragility of such gains when control efforts are weakened. At present there are several countries reliant on organophosphates and carbamates for IRS, and increasing incipient resistance is a serious threat that could result in IRS no longer being viable. A portfolio of new cost-effective insecticides with different modes of action is urgently needed

    Species shifts in the Anopheles gambiae complex: do LLINs successfully control Anopheles arabiensis?

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    INTRODUCTION: High coverage of conventional and long-lasting insecticide treated nets (ITNs and LLINs) in parts of E Africa are associated with reductions in local malaria burdens. Shifts in malaria vector species ratio have coincided with the scale-up suggesting that some species are being controlled by ITNs/LLINs better than others. METHODS: Between 2005-2006 six experimental hut trials of ITNs and LLINs were conducted in parallel at two field stations in northeastern Tanzania; the first station was in Lower Moshi Rice Irrigation Zone, an area where An. arabiensis predominates, and the second was in coastal Muheza, where An. gambiae and An. funestus predominate. Five pyrethroids and one carbamate insecticide were evaluated on nets in terms of insecticide-induced mortality, blood-feeding inhibition and exiting rates. RESULTS: In the experimental hut trials mortality of An. arabiensis was consistently lower than that of An. gambiae and An. funestus. The mortality rates in trials with pyrethroid-treated nets ranged from 25-52% for An. arabiensis, 63-88% for An. gambiae s.s. and 53-78% for An. funestus. All pyrethroid-treated nets provided considerable protection for the occupants, despite being deliberately holed, with blood-feeding inhibition (percentage reduction in biting rates) being consistent between species. Veranda exiting rates did not differ between species. Percentage mortality of mosquitoes tested in cone bioassays on netting was similar for An. gambiae and An. arabiensis. CONCLUSIONS: LLINs and ITNs treated with pyrethroids were more effective at killing An. gambiae and An. funestus than An. arabiensis. This could be a major contributing factor to the species shifts observed in East Africa following scale up of LLINs. With continued expansion of LLIN coverage in Africa An. arabiensis is likely to remain responsible for residual malaria transmission, and species shifts might be reported over larger areas. Supplementary control measures to LLINs may be necessary to control this vector species

    Biochemical basis of permethrin resistance in Anopheles arabiensis from Lower Moshi, north-eastern Tanzania.

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    BACKGROUND: Development of resistance to different classes of insecticides is a potential threat to malaria control. With the increasing coverage of long-lasting insecticide-treated nets in Tanzania, the continued monitoring of resistance in vector populations is crucial. It may facilitate the development of novel strategies to prevent or minimize the spread of resistance. In this study, metabolic-based mechanisms conferring permethrin (pyrethroid) resistance were investigated in Anopheles arabiensis of Lower Moshi, Kilimanjaro region of north-eastern Tanzania. METHODS: WHO susceptibility test kits were used to detect resistance to permethrin in An. arabiensis. The levels and mechanisms of permethrin resistance were determined using CDC bottle bioassays and microplate (biochemical) assays. In bottle bioassays, piperonyl butoxide (PBO) and s,s,s-tributyl phosphorotrithioate (DEF) were used as synergists to inhibit mixed function oxidases and non-specific esterases respectively. Biochemical assays were carried out in individual mosquitoes to detect any increase in the activity of enzymes typically involved in insecticide metabolism (mixed function oxidases, alpha- and beta-esterases). RESULTS: Anopheles arabiensis from the study area was found to be partially resistant to permethrin, giving only 87% mortality in WHO test kits. Resistance ratios at KT50 and KT95 were 4.0 and 4.3 respectively. The permethrin resistance was partially synergized by DEF and by PBO when these were mixed with permethrin in bottle bioassays and was fully synergized when DEF and PBO were used together. The levels of oxidase and beta-esterase activity were significantly higher in An. arabiensis from Lower Moshi than in the laboratory susceptible strain. There was no difference in alpha-esterase activity between the two strains. CONCLUSION: Elevated levels of mixed function oxidases and beta-esterases play a role in detoxification of permethrin in the resistant An. arabiensis population of Lower Moshi

    Indoor residual spraying with microencapsulated DEET repellent (N, N-diethyl-m-toluamide) for control of Anopheles arabiensis and Culex quinquefasciatus.

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    BACKGROUND: Evolution of insecticide resistance in Anopheles gambiae complex necessitates evaluation of alternative chemical classes to complement existing insecticides for long lasting insecticidal nets (LLIN) and indoor residual spraying (IRS). Microencapsulated (MC) DEET (N, N-diethyl-m-toluamide) is a formulation of the popular repellent, which gives long lasting activity when applied to nets. Its suitability for IRS use has not been evaluated before. This study assessed the efficacy of DEET MC, for IRS in experimental huts. METHODS: DEET MC was tested alongside standard repellent and non-repellent residual insecticides: lambdacyhalothrin, permethrin, pirimiphos methyl and DDT. Residual formulations of these compounds were sprayed on plywood panels attached to walls of experimental huts to assess efficacy against pyrethroid resistant, wild free-flying Anopheles arabiensis and Culex quinquefasciatus. The panel treatments were rotated weekly between huts. RESULTS: The overall mortalities of An. arabiensis induced by the various treatments (range: 76-86%) were significantly greater than mortality in the untreated control (8%, P < 0.001). Mortality of An. arabiensis in DEET sprayed huts (82%) was higher than in lambdacyhalothrin CS (76%, P = 0.043) but not significantly different to pirimiphos methyl CS (86%, P = 0.204) or DDT huts (81%, P = 0.703). Against Cx. quinquefasciatus DEET MC was less effective, inducing lower mortality (29%) than other treatments. An arabiensis blood feeding rates were higher in the unsprayed control (34%) than in sprayed huts (range between treatments: 19-22%, P < 0.002), and DEET provided equivalent or superior blood feeding inhibition (44%) to other insecticides. Against Cx. quinquefasciatus there was no significant reduction in blood-feeding for any treatment relative to the control. There was a significantly higher exiting of An. arabiensis from huts sprayed with DEET (98%), lambdacyhalothrin (98%) and permethrin (96%) relative to the control (80%, P < 0.01). Exiting rates of Cx. quinquefasciatus did not differ between treatment huts and the control. CONCLUSION: Microencapsulated DEET acts like an insecticide at ambient temperature and induces mosquito mortality when applied to walls made from wooden panels. This trial demonstrated the potential of microencapsulated DEET to control An. arabiensis and warrants further studies of residual activity on interior substrates

    Troponin release following endurance exercise: is inflammation the cause? a cardiovascular magnetic resonance study

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    Background: The aetiology and clinical significance of troponin release following endurance exercise is unclear but may be due to transient myocardial inflammation. Cardiovascular magnetic resonance (CMR) affords us the opportunity to evaluate the presence of myocardial inflammation and focal fibrosis and is the ideal imaging modality to study this hypothesis. We sought to correlate the relationship between acute bouts of ultra endurance exercise leading to cardiac biomarkers elevation and the presence of myocardial inflammation and fibrosis using CMR.Methods: 17 recreation athletes (33.5 +/- 6.5 years) were studied before and after a marathon run with troponin, NTproBNP, and CMR. Specific imaging parameters to look for inflammation included T2 weighted images, and T1 weighted spin-echo images before and after an intravenous gadolinium-DTPA to detect myocardial hyperemia secondary to inflammation. Late gadolinium imaging was performed (LGE) to detect any focal regions of replacement fibrosis.Results: Eleven of the 17 participant had elevations of TnI above levels of cut off for myocardial infarction 6 hrs after the marathon (0.075 +/- 0.02, p = 0.007). Left ventricular volumes were reduced post marathon and a small increase in ejection fraction was noted (64 +/- 1% pre, 67 +/- 1.2% post, P = 0.014). Right ventricular volumes, stroke volume, and ejection fraction were unchanged post marathon. No athlete fulfilled criteria for myocardial inflammation based on current criteria. No regions of focal fibrosis were seen in any of the participants.Conclusion: Exercise induced cardiac biomarker release is not associated with any functional changes by CMR or any detectable myocardial inflammation or fibrosis

    A new class of insecticide for malaria vector control: evaluation of mosquito nets treated singly with indoxacarb (oxadiazine) or with a pyrethroid mixture against Anopheles gambiae and Culex quinquefasciatus.

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    BACKGROUND: Universal coverage with long-lasting insecticidal mosquito nets (LLIN) or indoor residual spraying (IRS) of houses remain the primary strategies for the control of mosquito vectors of malaria. Pyrethroid resistant malaria vectors are widespread throughout sub-Saharan Africa and new insecticides with different modes of action are urgently needed if malaria vector control is to remain effective. Indoxacarb is an oxadiazine insecticide that is effective as an oral and contact insecticide against a broad spectrum of agricultural pests and, due to its unique site of action, no cross-resistance has been detected through mechanisms associated with resistance to insecticides currently used in public health. METHODS: WHO tunnel tests of host seeking mosquitoes were carried out as a forerunner to experimental hut trials, to provide information on dosage-dependent mortality, repellency, and blood-feeding inhibition. A dosage range of indoxacarb treated netting (100-1000 mg/m(2)) was tested against a pyrethroid susceptible strain of Anopheles gambiae. In addition, efficacy of indoxacarb 500 mg/m(2) was compared with a standard pyrethroid formulation against pyrethroid susceptible and resistant Culex quinquefasciatus. Dosages between 25 and 300 mg/m(2) indoxacarb were tested in tunnel tests and in ball-frame bioassays as mixtures with alphacypermethrin 25 mg/m(2) and were compared with singly applied treatments against an insectary reared pyrethroid resistant strain of Cx. quinquefasciatus originally collected in Cotonou, Benin. RESULTS: There was a dosage-dependent response in terms of indoxacarb induced mortality, with dosages >100 mg/m(2) producing the best mortality response. In tunnel tests indoxacarb 500 mg/m(2) exceeded WHOPES thresholds with >80 % mortality of adult An. gambiae and blood-feeding inhibition of 75 %. No cross-resistance to indoxacarb was detected through mechanisms associated with resistance to pyrethroid insecticides and was equally effective against susceptible and resistant strains of Cx. quinquefasciatus. Indoxacarb 500 mg/m(2) killed 75 % of pyrethroid resistant Cx. quinquefasciatus compared with only 21 % mortality with alphacypermethrin 40 mg/m(2). Mixtures of indoxacarb with pyrethroid produced an additive response for both mortality and blood-feeding inhibition. The best performing mixture (indoxacarb 200 mg/m(2) + alphacypermethrin 25 mg/m(2)) killed 83 % of pyrethroid resistant Cx. quinquefasciatus and reduced blood-feeding by 88 %, while alphacypermethrin only killed 36 % and inhibited blood-feeding by 50 %. CONCLUSIONS: New insecticides with different modes of action to those currently used in mosquito vector control are urgently needed. Indoxacarb shows great promise as a mixture with a pyrethroid and should be evaluated in experimental hut trials to determine performance against wild free-flying, pyrethroid resistant An. gambiae and wash-resistant formulations developed

    ITN mixtures of chlorfenapyr (Pyrrole) and alphacypermethrin (Pyrethroid) for control of pyrethroid resistant Anopheles arabiensis and Culex quinquefasciatus.

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    Pyrethroid resistant Anopheles gambiae malaria vectors are widespread throughout sub-Saharan Africa and continued efficacy of pyrethroid ITNs is under threat. Chlorfenapyr is a promising pyrrole insecticide with a unique mechanism of action conferring no cross-resistance to existing public health insecticides. Mixtures of chlorfenapyr (CFP) and alphacypermethrin (alpha) may provide additional benefits over chlorfenapyr or alphacypermethrin used alone. An ITN mixture of CFP 100 mg/m(2)+alpha 25 mg/m(2) was compared with CFP 100 mg/m(2) and alpha 25 mg/m(2) in a small-scale experimental hut trial in an area of wild An. arabiensis. The same treatments were evaluated in tunnel tests against insectary-reared pyrethroid susceptible and resistant Culex quinquefasciatus. Performance was measured in terms of insecticide-induced mortality, and blood-feeding inhibition. Tunnel tests showed that mixtures of CFP 100+ alpha 25 were 1.2 and 1.5 times more effective at killing susceptible Cx. quinquefasciatus than either Alpha 25 (P = 0.001) or CFP 100 (P = 0.001) ITNs. Mixtures of CFP100+ alpha 25 were 2.2 and 1.2 times more effective against resistant Cx. quinquefasciatus than either alpha 25 (P = 0.001) or CFP100 (P = 0.003) ITNs. CFP 100+ alpha 25 produced higher levels of blood-feeding inhibition than CFP alone for susceptible (94 vs 46%, P = 0.001) and resistant (84 vs 53%, P = 0.001) strains. In experimental huts the mixture of CFP 100+ Alpha 25 killed 58% of An. arabiensis, compared with 50% for alpha and 49% for CFP, though the differences were not significant. Blood-feeding inhibition was highest in the mixture with a 76% reduction compared to the untreated net (P = 0.001). ITN mixtures of chlorfenapyr and alphacypermethrin should restore effective control of resistant populations of An. gambiae malaria vectors, provide protection from blood-feeding, and may have benefits for resistance management, particularly in areas with low or moderate frequency of pyrethroid resistance. A wash-resistant mixture should be developed urgently
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