A deltamethrin crystal polymorph for more effective malaria control.
Ontology highlight
ABSTRACT:
SUBMITTER: Yang J
PROVIDER: S-EPMC7604418 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Malaria continues to impose a substantial burden on human health. We have previously proposed that biological approaches to control the mosquito vector of disease could be developed using homing endonuclease genes (HEGs), a class of selfish or parasitic gene that exists naturally in many microbes. Recent lab studies have demonstrated that HEGs can function in mosquitoes. We constructed and analyzed a model of mosquito population genetics and malaria epidemiology to determine how well HEGs need to function in order to have a significant effect on the burden of disease. Our model, combined with currently available data, indicates that populations of Anopheles gambiae could be eliminated by releasing 2-3 HEGs targeting female fertility genes, or a driving-Y chromosome that is transmitted to 75-96% of progeny. Combinations of fertility-targeting HEGs and Y drive may also be effective. It is possible to eliminate the disease without eliminating the vector, but the parameter space producing this outcome appears to be small. HEGs causing a quantitative reduction in adult survival can be more effective than those targeting female fertility, but the selection coefficients that need to be imposed are still large, unless many HEGs are to be released. Simulations show that HEG-based strategies can be effective over socially relevant time frames. Important limiting assumptions of the models are that there is only a single vector species, and we model a homogeneous population, not a landscape. Nevertheless, we conclude that HEG-based approaches could have a transformational effect on malaria control efforts.
| S-EPMC3203790 | biostudies-literature
Project description:Malaria vectors in sub-Saharan Africa have proven themselves very difficult adversaries in the global struggle against malaria. Decades of anti-vector interventions have yielded mixed results--with successful reductions in transmission in some areas and limited impacts in others. These varying successes can be ascribed to a lack of universally effective vector control tools, as well as the development of insecticide resistance in mosquito populations. Understanding the impact of vector control on mosquito populations is crucial for planning new interventions and evaluating existing ones. However, estimates of population size changes in response to control efforts are often inaccurate because of limitations and biases in collection methods. Attempts to evaluate the impact of vector control on mosquito effective population size (N(e)) have produced inconclusive results thus far. Therefore, we obtained data for 13-15 microsatellite markers for more than 1,500 mosquitoes representing multiple time points for seven populations of three important vector species--Anopheles gambiae, An. melas, and An. moucheti--in Equatorial Guinea. These populations were exposed to indoor residual spraying or long-lasting insecticidal nets in recent years. For comparison, we also analyzed data from two populations that have no history of organized vector control. We used Approximate Bayesian Computation to reconstruct their demographic history, allowing us to evaluate the impact of these interventions on the effective population size. In six of the seven study populations, vector control had a dramatic impact on the effective population size, reducing N(e) between 55%-87%, the exception being a single An. melas population. In contrast, the two negative control populations did not experience a reduction in effective population size. This study is the first to conclusively link anti-vector intervention programs in Africa to sharply reduced effective population sizes of malaria vectors.
| S-EPMC3521722 | biostudies-literature
Project description:3D electron diffraction (3DED) has been used to follow polymorph evolution in the crystallization of glycine from aqueous solution. The three polymorphs of glycine which exist under ambient conditions follow the stability order ? < ? < ?. The least stable ? polymorph forms within the first 3?min, but this begins to yield the ?-form after only 1?min more. Both structures could be determined from continuous rotation electron diffraction data collected in less than 20?s on crystals of thickness ?100?nm. Even though the ?-form is thermodynamically the most stable polymorph, kinetics favour the ?-form, which dominates after prolonged standing. In the same sample, some ? and one crystallite of the ? polymorph were also observed.
| S-EPMC6949601 | biostudies-literature
Project description:The title mol-ecular salt, C6H8N(+)·C6H2N3O7 (-) (systematic name: 3-methyl-pyridinium 2,4,6-tri-nitro-phenolate), crystallizes in the triclinic space group P-1. The crystal structure of the monoclinic polymorph (space group P21/n) has been reported [Stilinovic & Kaitner (2011 ▸). Cryst. Growth Des. 11, 4110-4119]. In the crystal, the anion and cation are linked via bifurcated N-H⋯(O,O) hydrogen bonds, enclosing an R 1 (2)(6) graph-set motif. These units are linked via C-H⋯O hydrogen bonds, forming a three-dimensional framework. Within the framework there are π-π inter-actions present, involving inversion-related picrate anions and inversion-related pyridinium cations, with inter-centroid distances of 3.7389 (14) and 3.560 (2) Å, respectively.
| S-EPMC4647397 | biostudies-literature
Project description:Since 2000, human malaria cases in Malaysia were rapidly reduced with the use of insecticides in Indoor Residual Spray (IRS) and Long-Lasting Insecticide Net (LLIN). Unfortunately, monkey malaria in humans has shown an increase especially in Sabah and Sarawak. The insecticide currently used in IRS is deltamethrin K-Othrine® WG 250 wettable granule, targeting mosquitoes that rest and feed indoor. In Sabah, the primary vector for knowlesi malaria is An. balabacensis a species known to bite outdoor. This study evaluates an alternative method, the Outdoor Residual Spray (ORS) using a novel formulation of deltamethrin K-Othrine® (PolyZone) to examine it suitability to control knowlesi malaria vector in Sabah, compared to the current method. The study was performed at seven villages in Sabah having similar type of houses (wood, bamboo and concrete). Houses were sprayed with deltamethrin K-Othrine® (PolyZone) at two different dosages, 25 mg/m2 and 30 mg/m2 and deltamethrin K-Othrine® WG 250 wettable granule at 25 mg/m2, sprayed indoor and outdoor. Residual activity on different walls was assessed using standard cone bioassay techniques. For larval surveillances, potential breeding sites were surveyed. Larvae were collected and identified, pre and post spraying. Adult survey was done using Human Landing Catch (HLC) performed outdoor and indoor. Detection of malaria parasite in adults was conducted via microscopy and molecular methods. Deltamethrin K-Othrine® (PolyZone) showed higher efficacy when sprayed outdoor. The efficacy was found varied when sprayed on different types of wall surfaces. Deltamethrin K-Othrine® (PolyZone) at 25 mg/m2 was the most effective with regards to ability to high mortality and effective knock down (KD). The vector population was reduced significantly post-spraying and reduction in breeding sites as well. The number of simian malaria infected vector, human and simian malaria transmission were also greatly reduced.
| S-EPMC7228059 | biostudies-literature
Project description:Two conformational polymorphs of novel 2-[2-(3-cyano-4,6-dimethyl-2-oxo-2H-pyridin-1-yl)-ethoxy]-4,6-dimethyl nicotinonitrile have been developed. The crystal structure of both polymorphs (1a and 1b) seems to be stabilized by weak interactions. A difference was observed in the packing of both polymorphs. Polymorph 1b has a better binding affinity with the cyclooxygenase (COX-2) receptor than the standard (Nimesulide).
| S-EPMC3821945 | biostudies-literature
Project description:In this work, the polymorphism of the active pharmaceutical ingredient carbamazepine (CBZ) was investigated by using molecular dynamics simulations with an enhanced sampling scheme. A single molecule of CBZ attaching to flat surfaces of different polymorphs was used as a model for secondary nucleation in water. A novel approach was developed to compute the free energy profile characterizing the adsorption of molecules with orientation aligned with the crystal structure of the surface. The distribution of states that showed alignment was used to rescale the adsorption free energy to include only the contribution that is consistent with crystal growth. The resulting free energy surfaces showed favorable thermodynamics for the most stable form, Form III and the second most stable form, Form I. The primary crystallization product, a dihydrate, was found to be less favorable, implying a nonclassical crystallization pathway. We suggest that a major contribution determining the energetics is the hydrophobicity of the surface. This thermodynamic ranking provides valuable information about the molecular pathways of polymorph growth and will further contribute to the understanding of the crystallization process of CBZ, which is imperative since polymorph formation can alter the physical properties of a drug significantly.
| S-EPMC11360048 | biostudies-literature
Project description:In an attempt to grow 8-hy-droxy-quinoline-acetamino-phen co-crystals from equimolar amounts of conformers in a chloro-form-ethanol solvent mixture at room temperature, the title compound, C9H7NO, was obtained. The mol-ecule is planar, with the hy-droxy H atom forming an intra-molecular O-H⋯N hydrogen bond. In the crystal, mol-ecules form centrosymmetric dimers via two O-H⋯N hydrogen bonds. Thus, the hy-droxy H atoms are involved in bifurcated O-H⋯N hydrogen bonds, leading to the formation of a central planar four-membered N2H2 ring. The dimers are bound by inter-molecular π-π stacking [the shortest C⋯C distance is 3.2997 (17) Å] and C-H⋯π inter-actions into a three-dimensional framework. The crystal grown represents a new monoclinic polymorph in the space group P21/n. The mol-ecular structure of the present monoclinic polymorph is very similar to that of the ortho-rhom-bic polymorph (space group Fdd2) studied previously [Roychowdhury et al. (1978 ▶). Acta Cryst. B34, 1047-1048; Banerjee & Saha (1986 ▶). Acta Cryst. C42, 1408-1411]. The structures of the two polymorphs are distinguished by the different geometries of the hydrogen-bonded dimers, which in the crystal of the ortho-rhom-bic polymorph possess twofold axis symmetry, with the central N2H2 ring adopting a butterfly conformation.
| S-EPMC4186174 | biostudies-literature
Project description:Nucleation plays a critical role in the birth of crystals and is associated with a vast array of phenomena, such as protein crystallization and ice formation in clouds. Despite numerous experimental and theoretical studies, many aspects of the nucleation process, such as the polymorph selection mechanism in the early stages, are far from being understood. Here, we show that the hitherto unexplained excess of particles in a face-centered-cubic (fcc)-like environment, as compared to those in a hexagonal-close-packed (hcp)-like environment, in a crystal nucleus of hard spheres can be explained by the higher order structure in the fluid phase. We show using both simulations and experiments that in the metastable fluid phase, pentagonal bipyramids, clusters with fivefold symmetry known to be inhibitors of crystal nucleation, transform into a different cluster, Siamese dodecahedra. These clusters are closely similar to an fcc subunit, which explains the higher propensity to grow fcc than hcp in hard spheres. We show that our crystallization and polymorph selection mechanism is generic for crystal nucleation from a dense, strongly correlated fluid phase.
| S-EPMC10173683 | biostudies-literature
Project description:BackgroundSymptomatic malaria cases reflect only a small proportion of all Plasmodium spp infections. Many infected individuals are asymptomatic, and persistent asymptomatic Plasmodium falciparum infections are common in endemic settings. We aimed to quantify the contribution of symptomatic and asymptomatic infections to P falciparum transmission in Tororo, Uganda.MethodsWe did a longitudinal, observational cohort study in Tororo district, Uganda. We recruited participants of all ages from randomly selected households within this district. Participants were eligible if the selected household had no more than nine permanent residents and at least two members younger than 10 years, and the household was their primary residence, and they agreed to come to the study clinic for any fever episode and avoid antimalarial medications outside the study. Participants were followed-up by continuous passive surveillance for the incidence of symptomatic infections; routine assessments (ie, standardised clinical evaluation and blood samples) were done at baseline and at routine visits every 4 weeks for 2 years. P falciparum parasite density, gametocyte density, and genetic composition were determined molecularly using quantitative PCR (qPCR), quantitative reverse transcriptase PCR (qRT-PCR), and amplicon deep sequencing, respectively. Membrane feeding assays were also done to assess infectivity to mosquitoes. The contribution of different populations to the infectious reservoir was estimated for symptomatic infections, asymptomatic but microscopically detected infections, and asymptomatic but qPCR-detected infections; and for age groups younger than 5 years, 5-15 years, and 16 years or older.FindingsBetween Oct 4, 2017, and Oct 31, 2019, 531 individuals were enrolled from 80 randomly selected households and were followed-up for 2 years. At baseline, P falciparum was detected in 28 (5·3%) of 531 participants by microscopy and an additional 64 (12·1%) by qPCR and declined thereafter. In 538 mosquito feeding experiments on 107 individuals, 446 (1·2%) of 37 404 mosquitoes became infected, with mosquito infection rates being strongly associated with gametocyte densities (β=2·11, 95% CI 1·62-2·67; p<0·0001). Considering both transmissibility of infections and their relative frequency, the estimated human infectious reservoir consisted primarily of asymptomatic microscopy-detected infections (83·8%), followed by asymptomatic submicroscopic infections (15·6%), and symptomatic infections (0·6%). Children aged 5-15 years accounted for more than half of the infectious reservoir (58·7%); individuals younger than 5 years (25·8%) and those 16 years or older (15·6%) contributed less. Samples from four children contribued to 279 (62·6%) of 446 infected mosquitoes after multiple mosquito-feeding assays.InterpretationIndividuals with asymptomatic infections were important drivers of malaria transmission. School-aged children contributed to more than half of all mosquito infections, with a small minority of asymptomatic children being highly infectious. Demographically targeted interventions, aimed at school-aged children, could further reduce transmission in areas under effective vector control.FundingUS National Institutes of Health, Bill & Melinda Gates Foundation, and the European Research Council.
| S-EPMC8554388 | biostudies-literature