Artemisinins: A group of SESQUITERPENES and their analogs that contain a peroxide group (PEROXIDES) within an oxepin ring (OXEPINS).Antimalarials: Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585)Parasitic Sensitivity Tests: Tests that demonstrate the relative effectiveness of chemotherapeutic agents against specific parasites.SesquiterpenesDrug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.Plasmodium falciparum: A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics.Malaria, Falciparum: Malaria caused by PLASMODIUM FALCIPARUM. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations.Malaria: A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia.Inhibitory Concentration 50: The concentration of a compound needed to reduce population growth of organisms, including eukaryotic cells, by 50% in vitro. Though often expressed to denote in vitro antibacterial activity, it is also used as a benchmark for cytotoxicity to eukaryotic cells in culture.Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.Drug Therapy, Combination: Therapy with two or more separate preparations given for a combined effect.Parasites: Invertebrate organisms that live on or in another organism (the host), and benefit at the expense of the other. Traditionally excluded from definition of parasites are pathogenic BACTERIA; FUNGI; VIRUSES; and PLANTS; though they may live parasitically.Fluorenes: A family of diphenylenemethane derivatives.Cameroon: A republic in central Africa lying east of CHAD and the CENTRAL AFRICAN REPUBLIC and west of NIGERIA. The capital is Yaounde.Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.Amodiaquine: A 4-aminoquinoline compound with anti-inflammatory properties.Ethanolamines: AMINO ALCOHOLS containing the ETHANOLAMINE; (-NH2CH2CHOH) group and its derivatives.Anti-HIV Agents: Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS.Antiretroviral Therapy, Highly Active: Drug regimens, for patients with HIV INFECTIONS, that aggressively suppress HIV replication. The regimens usually involve administration of three or more different drugs including a protease inhibitor.HIV Infections: Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).BooksNobel PrizeHistory, 20th Century: Time period from 1901 through 2000 of the common era.History, 21st Century: Time period from 2001 through 2100 of the common era.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.Book SelectionJournal Impact Factor: A quantitative measure of the frequency on average with which articles in a journal have been cited in a given period of time.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues.Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from INCIDENCE, which refers to the number of new cases in the population at a given time.Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with LONGITUDINAL STUDIES which are followed over a period of time.Dietary Supplements: Products in capsule, tablet or liquid form that provide dietary ingredients, and that are intended to be taken by mouth to increase the intake of nutrients. Dietary supplements can include macronutrients, such as proteins, carbohydrates, and fats; and/or MICRONUTRIENTS, such as VITAMINS; MINERALS; and PHYTOCHEMICALS.Dapsone: A sulfone active against a wide range of bacteria but mainly employed for its actions against MYCOBACTERIUM LEPRAE. Its mechanism of action is probably similar to that of the SULFONAMIDES which involves inhibition of folic acid synthesis in susceptible organisms. It is also used with PYRIMETHAMINE in the treatment of malaria. (From Martindale, The Extra Pharmacopoeia, 30th ed, p157-8)Proguanil: A biguanide compound which metabolizes in the body to form cycloguanil, an anti-malaria agent.Pyrimethamine: One of the FOLIC ACID ANTAGONISTS that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis.Sulfadoxine: A long acting sulfonamide that is used, usually in combination with other drugs, for respiratory, urinary tract, and malarial infections.Atlantic Islands: Widely scattered islands in the Atlantic Ocean as far north as the AZORES and as far south as the South Sandwich Islands, with the greatest concentration found in the CARIBBEAN REGION. They include Annobon Island, Ascension, Canary Islands, Falkland Islands, Fernando Po (also called Isla de Bioko and Bioko), Gough Island, Madeira, Sao Tome and Principe, Saint Helena, and Tristan da Cunha.BrazilLibrary Collection Development: Development of a library collection, including the determination and coordination of selection policy, assessment of needs of users and potential users, collection use studies, collection evaluation, identification of collection needs, selection of materials, planning for resource sharing, collection maintenance and weeding, and budgeting.Allied Health Occupations: Occupations of medical personnel who are not physicians, and are qualified by special training and, frequently, by licensure to work in supporting roles in the health care field. These occupations include, but are not limited to, medical technology, physical therapy, physician assistant, etc.Wasps: Any of numerous winged hymenopterous insects of social as well as solitary habits and having formidable stings.Lymphangiogenesis: The formation of LYMPHATIC VESSELS.Praziquantel: An anthelmintic used in most schistosome and many cestode infestations.Schistosoma mansoni: A species of trematode blood flukes of the family Schistosomatidae. It is common in the Nile delta. The intermediate host is the planorbid snail. This parasite causes schistosomiasis mansoni and intestinal bilharziasis.Vascular Endothelial Growth Factor A: The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.Image Processing, Computer-Assisted: A technique of inputting two-dimensional images into a computer and then enhancing or analyzing the imagery into a form that is more useful to the human observer.Schistosomicides: Agents that act systemically to kill adult schistosomes.Anthelmintics: Agents destructive to parasitic worms. They are used therapeutically in the treatment of HELMINTHIASIS in man and animal.Robotics: The application of electronic, computerized control systems to mechanical devices designed to perform human functions. Formerly restricted to industry, but nowadays applied to artificial organs controlled by bionic (bioelectronic) devices, like automated insulin pumps and other prostheses.Equipment Design: Methods of creating machines and devices.Semiconductors: Materials that have a limited and usually variable electrical conductivity. They are particularly useful for the production of solid-state electronic devices.Patents as Topic: Exclusive legal rights or privileges applied to inventions, plants, etc.Posture: The position or attitude of the body.DNA Probes: Species- or subspecies-specific DNA (including COMPLEMENTARY DNA; conserved genes, whole chromosomes, or whole genomes) used in hybridization studies in order to identify microorganisms, to measure DNA-DNA homologies, to group subspecies, etc. The DNA probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the DNA probe include the radioisotope labels 32P and 125I and the chemical label biotin. The use of DNA probes provides a specific, sensitive, rapid, and inexpensive replacement for cell culture techniques for diagnosing infections.Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of SILICON DIOXIDE. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight [28.084; 28.086].

Declining concentrations of dihydroartemisinin in plasma during 5-day oral treatment with artesunate for Falciparum malaria. (1/1442)

Six patients with uncomplicated falciparum malaria received artesunate for 5 days. Plasma concentrations of artesunate and dihydroartemisinin were determined by high-performance liquid chromatography with electrochemical detection. The concentrations of dihydroartemisinin in plasma 2 h after a dose showed a time-dependent decline. Concentrations of artesunate in plasma especially after the last dose, were very low. Despite this, all patients responded with a fast recovery.  (+info)

A randomized, double-blind, comparative trial of a new oral combination of artemether and benflumetol (CGP 56697) with mefloquine in the treatment of acute Plasmodium falciparum malaria in Thailand. (2/1442)

CGP 56697, a new oral fixed combination of artemether and benflumetol, was tested in a double-blinded, randomized trial in 252 adult patients treated either with CGP 56697 (4 x 4 tablets each containing 20 mg of artemether and 120 mg of benflumetol, given at 0, 8, 24, and 48 hr), or with mefloquine (three tablets of 250 mg at initial diagnosis, followed by two tablets of 250 mg at 8 hr). Baseline data of the two groups were comparable. The 28-day cure rate with CGP 56697 was lower than with mefloquine (69.3% versus 82.4%; P = 0.002). However, CGP 56697 was more effective than mefloquine in parasite clearance time (43 hr versus 66 hr; P < 0.001) fever clearance time (32 hr versus 54 hr; P < 0.005), and gametocyte clearance time (152 hr versus 331 hr; P < 0.001). This study revealed that CGP 56697 is effective against multidrug-resistant Plasmodium falciparum malaria in Thailand, but higher doses will probably be needed to improve the cure rate.  (+info)

The pharmacokinetics of artemisinin after administration of two different suppositories to healthy Vietnamese subjects. (3/1442)

Eight healthy Vietnamese male subjects received 400 mg artemisinin formulated into fatty suppositories (FS), and six different subjects received 500 mg of artemisinin formulated in polyethylene glycol suppositories (PEGS). Plasma concentrations were measured by high-performance liquid chromatography with electrochemical detection; concentration versus time curves were analyzed with nonparametric methods. No statistically significant differences were found between the two formulations. The maximum concentration (Cmax) was 100 +/- 102 microg/L (mean +/- SD, range = 24-330) microg/L (FS), the pharmacokinetic lag time (Tlag) was 1.3 +/- 1.0 hr (range = 0-3) (FS), and the time of the maximum concentration (Tmax) was 7.1 +/- 2.1 hr (range = 3-10) hr (FS). Because artemisinin is not available for intravenous dosage, absolute bioavailability cannot be assessed. However, compared with a previous study on oral artemisinin in healthy Vietnamese subjects, bioavailability relative to oral administration was estimated to be approximately 30%. We conclude that therapeutic blood concentrations of artemisinin can be reached after rectal dosage. The dose after rectal administration should probably be higher than after oral administration; doubling or tripling the oral dose might be necessary, which would imply a rectal dose of at least 20 mg/kg of body weight given twice a day.  (+info)

Effect of artemether on glucose uptake and glycogen content in Schistosoma japonicum. (4/1442)

AIM: To study the effect of artemether (Art) on glucose uptake and glycogen content in schistosomes. METHODS: Schistosomes recovered from mice treated intragastrically with Art 300 mg.kg-1 for 24-48 h, were incubated in the drug-free medium containing [U-14C]glucose 11.1 MBq.L-1. The glycogen content, [U-14C]glucose uptake, and incorporation of [U-14C]glucose into worm glycogen in both male and female worms were determined. RESULTS: When above-mentioned schistosomes were exposed to drug-free medium containing [U-14C]glucose for 1-24 h, the glycogen contents of male and female worms decreased 27%-61% and 39%-78%, respectively. Only 3 out of 6 male worm groups showed 23%-35% decrease in glucose uptake, while much less glucose uptake was found in female worms in all groups with reduction rates of 18%-38%. Apart from 2 male groups no apparent change in the incorporation of [U-14C]glucose into the worm glycogen was seen. CONCLUSIONS: Art-induced glycogen reduction in schistosomes was related to an inhibition of glycolysis rather than an interference with glucose uptake.  (+info)

Inhibitory effect of artemether on proteinase of Schistosoma japonicum. (5/1442)

AIM: To study the effect of artemether (Art) on the thio proteinase ("hemoglobinase", Hem) of Schistosoma japonicum. METHODS: Hem was extracted from S japonicum adults. The inhibitory effect of Art on the activity of Hem to degrade human hemoglobin (Hgb) was examined with UV-photometer at 280 nm, SDS-PAGE and scanning at 600 nm on a chromoscanner. RESULTS: Human Hgb was degraded at pH 4.0 by the Hem. The activities of Hem preincubated at 37 degrees C with Art 0.14, 1.4, and 14 mmol.L-1, were inhibited by 30.2%, 39.8%, and 45.0%, respectively. CONCLUSION: Art possesses an inhibitory effect to Hem of S japonicum.  (+info)

Metabolism of the antimalarial endoperoxide Ro 42-1611 (arteflene) in the rat: evidence for endoperoxide bioactivation. (6/1442)

Ro 42-1611 (arteflene) is a synthetic endoperoxide antimalarial. The antimalarial activity of endoperoxides is attributed to iron(II)-mediated generation of carbon-centered radicals. An alpha, beta-unsaturated ketone (enone; 4-[2',4' bis(trifluoromethyl)phenyl]-3-buten-2-one), obtained from arteflene by reaction with iron(II), was identified previously as the stable product of a reaction that, by inference, also yields a cyclohexyl radical. The activation of arteflene in vivo has been characterized with particular reference to enone formation. [14C]Arteflene (35 micromol/kg) was given i.v. to anesthetized and cannulated male rats: 42.2 +/- 7.0% (mean +/- S.D., n = 7) of the radiolabel was recovered in bile over 5 h. In the majority of rats, the principal biliary metabolites were 8-hydroxyarteflene glucuronide (14.2 +/- 3. 9% dose, 0-3 h) and the cis and trans isomers of the enone (13.5 +/- 4.6% dose, 0-3 h). In conscious rats, 15.3 +/- 1.6% (mean +/- S.D., n = 8) of the radiolabel was recovered in urine over 24 h. The principal urinary metabolite appeared to be a glycine conjugate of a derivative of the enone. Biliary excretion of the glucuronide, but not of the enones, was inhibited by ketoconazole. 8-Hydroxyarteflene was formed extensively by rat and human liver microsomes but no enone was found. Bioactivation is a major pathway of arteflene's metabolism in the rat. Although the mechanism of in vivo bioactivation is unclear, the reaction is not catalyzed by microsomal cytochrome P-450 enzymes.  (+info)

Artemether for severe malaria: a meta-analysis of randomized clinical trials. (7/1442)

The treatment of choice for severe malaria is quinine. However, a gradual progression of resistance to quinine has become a concern in parts of the world. Artemisinin-related compounds are a relatively new class of drugs. This meta-analysis assesses the evidence regarding the clinical effectiveness of artemether for severe malaria. Computerized literature searches identified all randomized clinical trials of artemether in comparison with quinine. Standardized data extraction was independently performed by both authors. Results of nine trials, entered in the meta-analysis, demonstrate the absence of a significant difference between artemether and quinine in terms of mortality rate (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.50-1.14). Statistical pooling of data from trials in Southeast Asia showed a trend toward enhanced reduction of mortality (OR, 0.38; 95% CI, 0.14-1.02). These data demonstrate the equality of artemether and quinine for severe malaria and indicate a trend toward greater effectiveness of artemether in regions where there is recognized quinine resistance.  (+info)

Cost-effectiveness analysis of artesunate and quinine + tetracycline for the treatment of uncomplicated falciparum malaria in Chanthaburi, Thailand. (8/1442)

A randomized, controlled, malaria-clinic-based field trial was carried out to compare the cost-effectiveness of a 5-day 700-mg oral artesunate and a 7-day quinine + tetracycline regimen for the treatment of uncomplicated falciparum malaria in Thailand. Cost-effectiveness was determined from the providers' perspective and based on curative effectiveness. A total of 137 patients, aged 15-60 years, attending a malaria clinic were followed for 28 days, 60 of them received quinine + tetracycline and 77 received artesunate. Cure rates were assessed on day 5 (artesunate) and day 7 (quinine + tetracycline), using the intention-to-treat approach. Cost-effectiveness and sensitivity analyses were performed by varying the day 5/day 7 curative effectiveness and cost of artesunate. The cure rate with artesunate (100%) was significantly higher than with quinine + tetracycline (77.4%) (relative risk adjusted for sex (aRR) = 1.32, 95% confidence interval (CI) = 1.12-1.55; referent quinine + tetracycline). Artesunate was more cost-effective than quinine + tetracycline at the following costs: artesunate, < or = US$0.36 per 50-mg tablet; quinine, US$0.06 per 300-mg tablet; tetracycline, US$0.02 per 250-mg capsule; and services per case found, < or = US$11.49. Because of the higher cure rate and higher cost-effectiveness of the artesunate regimen compared with quinine + tetracycline, we recommend its use for the treatment of uncomplicated falciparum malaria in malaria clinics in Thailand.  (+info)

BACKGROUND: Gametocytes are responsible for transmission of malaria from human to mosquito. Artemisinin combination therapy (ACT) reduces post-treatment gametocyte carriage, dependent upon host, parasite and pharmacodynamic factors. The gametocytocidal properties of antimalarial drugs are important for malaria elimination efforts. An individual patient clinical data meta-analysis was undertaken to identify the determinants of gametocyte carriage and the comparative effects of four ACTs: artemether-lumefantrine (AL), artesunate/amodiaquine (AS-AQ), artesunate/mefloquine (AS-MQ), and dihydroartemisinin-piperaquine (DP). METHODS: Factors associated with gametocytaemia prior to, and following, ACT treatment were identified in multivariable logistic or Cox regression analysis with random effects. All relevant studies were identified through a systematic review of PubMed. Risk of bias was evaluated based on study design, methodology, and missing data. RESULTS: The systematic review identified 169 published
Background: In Tanzania, many people seek malaria treatment from retail drug sellers. The National Malaria Control Program identified the accredited drug dispensing outlet (ADDO) program as a private sector mechanism to supplement the distribution of subsidized artemisinin-based combination therapies (ACTs) from public facilities and increase access to the first-line antimalarial in rural and underserved areas. The ADDO program strengthens private sector pharmaceutical services by improving regulatory and supervisory support, dispenser training, and record keeping practices.. Methods: The governments pilot program made subsidized ACTs available through ADDOs in 10 districts in the Morogoro and Ruvuma regions, covering about 2.9 million people. The program established a supply of subsidized ACTs, created a price system with a cost recovery plan, developed a plan to distribute the subsidized products to the ADDOs, trained dispensers, and strengthened the adverse drug reactions reporting system. ...
This multi-agency report, led by MSH, with input from CHAI, FIND, MMV, JSI/Deliver, PMI, RBM, WDI and WHO provides guidance for the specific interaction between artemisinin-based combination therapies (ACTs) and rapid diagnostic tests (RDTs). It shows users how to develop a stepwise approach to quantifying ACT and RDT demand at the program level and to understand the data and the assumptions that are needed for quantification, especially when the data are imperfect.. Specifically, the manual illustrates how to plan, forecast, and ensure supplies of ACTs and RDTs through the following steps: ...
According to the World Health Organization (WHO) estimates, released in December 2014, there were about 198 million cases of malaria in 2013 and an estimated 584,000 deaths. The burden is heaviest in the WHO African Region, where an estimated 90 % of all malaria deaths occur, and in children under 5 years of age, who account for 78 % of all deaths [1]. Early effective treatment of malaria is the cornerstone of malaria control. Plasmodium resistance to anti-malarial medicines is one of the major obstacles in the fight against malaria. Artemisinin combination therapy (ACT) is the WHO-recommended first-line treatment for uncomplicated falciparum malaria in all endemic regions [2, 3].. The clinical effectiveness of the artemisinin derivatives in ACT is due to rapid clearance of parasitaemia and rapid resolution of symptoms, by reducing parasite numbers. However, artemisinin derivatives are derived from plant source, so harvesting and extraction costs remain variable. This leads to fluctuation in the ...
THE KELCH PROPELLER HYPOTHESIS. Over the last century all monotherapies (quinine, chloroquine, mefloquine, pyrimethamine, halofantrine,methylene blue, lumefantrine) have lead to rapid resistances of Plasmodium falciparum. Combination therapy betweeen artemisinin and molecules with long lasting action had raised optimism. But already in 2003 first signs of resistance developed in South-East Asia. It has been established meanwhile that they were mostly related to mutations in the kelch13 propeller region of the parasite. Mutations have meanwhile raised to 90%. (Timothy J.C. Anderson, Shalini Nair, Marina McDew-White, Ian H. Cheeseman, Standwell Nkhoma, Fatma Bilgic, Rose McGready, Elizabeth Ashley, Aung Pyae Phyo, Nicholas J. White, François Nosten. Why are there so many independent origins of artemisinin resistance in malaria parasites? bioRxiv preprint first posted online May. 31, 2016; doi: http://dx.doi.org/10.1101/056291).. Artemisinin resistance in Plasmodium falciparum has emerged in ...
It is generally agreed that artemisinin-based combination therapy (ACT) is the malaria therapy of choice but there is much less agreement about the best ACT-deployment strategies. Countries are now beginning to adopt policies to enhance ACT deployment that aim to address 2 key goals: (i) making ACTs more readily and speedily accessible to patients: or (ii) targeting ACTs to patients shown to have malaria parasitaemia.. The Tanzanian Government has secured funding to address both ACT access and targeting on a national scale. Access is to be improved through the distribution of subsidised ACTs through private facilities and retail drug shops under the Affordable Medicines Facility-malaria (AMFm). Targeting is to be addressed through enhancing microscopy and introducing rapid diagnostic tests (RDTs) in health facilities at every level of the system.. This study will evaluate these two interventions in 3 rural regions of Tanzania which are all expected to receive both interventions during the study ...
Over the years, reports implicate improper anti-malarial use as a major contributor of morbidity and mortality amongst millions of residents in malaria endemic areas, Kenya included. However, there are limited reports on improper use of Artemisinin-based Combination Therapy (ACT) which is a first-line drug in the treatment of malaria in Kenya. Knowing this is important for ensured sustainable cure rates and also protection against the emergence of resistant malarial parasites. We therefore investigated ACT adherence level, factors associated with non-adherence and accessibility in households (n = 297) in rural location of Southeast Alego location in Siaya County in western Kenya. ACT Adherence level was assessed with reference to the duration of treatment and number of tablets taken. Using systematic random sampling technique, a questionnaire was administered to a particular household member who had the most recent malaria episode (|2 weeks) and used ACT for cure. Parents/caretakers provided information
The costs of delivering specific products are poorly understood and ballpark estimates are often used to inadequately plan for the budgetary implications of supply chain expenses. The purpose of this research was to estimate the country level costs of the public sector supply chain for artemisinin-based combination therapy (ACT) and rapid diagnostic tests (RDTs) from the central to the peripheral levels in Benin and Kenya. A micro-costing approach was used and primary data on the various cost components of the supply chain was collected at the central, intermediate, and facility levels between September and November 2013. Information sources included central warehouse databases, health facility records, transport schedules, and expenditure reports. In Benin, supply chain costs added US$0.20 to the initial acquisition cost of ACT and US$0.34 to RDTs; in Kenya, they added US$0.24 to the acquisition cost of ACT and US$0.19 to RDTs (normalized to US$1). Total supply chain costs accounted for more ...
From chloroquine to artemisinin-based combination therapy: the Sudanese experience. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Naturally acquired immunity can reduce parasitaemia and potentially influence anti-malarial treatment outcomes; however, evidence for this in the current literature provides conflicted results. The available evidence was synthesized to determine and quantify the association between host immunity and anti-malarial treatment failure. Four databases were searched to identify studies investigating malaria antibody levels in patients receiving anti-malarial treatment for symptomatic malaria with treatment failure recorded according to the World Health Organization classification. Odds ratios or hazard ratios were extracted or calculated to quantify the association between malarial antibody levels and treatment failure, and findings from different studies were visualized using forest plots. Eight studies, including patients with falciparum malaria treated with mono- and combination therapy of artemisinin derivatives, sulfadoxine, pyrimethamine and chloroquine, were identified. Reported and calculated effect
Artemisinin-based combination therapy (ACT) is used extensively as first-line treatment for uncomplicated falciparum malaria. There has been no rigorous assessment of the potential for racial/ethnic differences in the pharmacokinetic properties of ACTs that might influence their efficacy. Areas covered: A comprehensive literature search was performed that identified 72 publications in which the geographical origin of the patients could be ascertained and the key pharmacokinetic parameters maximum drug concentration (Cmax), area under the plasma concentration-time curve (AUC) and elimination half-life (t½β) were available for one or more of the five WHO-recommended ACTs (artemether-lumefantrine, artesunate-amodiaquine, artesunate-mefloquine, dihydroartemisinin-piperaquine and artesunate-sulfadoxine-pyrimethamine ...
Artemisinin-based combination therapies (ACTs) are now the treatment of choice for malaria in non-pregnant individuals living in areas with established chloroquine resistance; they have been shown to be both safe and highly efficacious. There is rapidly increasing experience with artemisinin derivatives in the 2nd and 3rd trimesters of pregnancy, with over 1,000 well documented cases with no reported serious adverse effects to mother or fetus (WHO Malaria Treatment Guidelines, 2006). Many countries in Latin America have abandoned the previous 1st line regimen of Quinine-Clindamycin for treatment of malaria in pregnancy, a complex and poorly tolerated regimen with low adherence, in favor of ACTs, despite limited safety and pharmacokinetic data on the use of these compounds in pregnant women. Lack of pharmacokinetic data may lead to underdosing of pregnant women, with subsequent reduced efficacy and increased potential for development of resistance.. One ACT regimen, Artesunate-Mefloquine, has ...
Artesunate is an anti-malarial drug with promising anti-inflammatory effects in allergic asthma. We investigated the protective effects of artesunate in experimental allergic asthma, in comparison to corticosteroids, dexamethasone. We demonstrate that artesunate possess favourable pharmacological effects against oxidative lung damage markers, 8-isoprostane, 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine. These effects include modulation of pulmonary antioxidants (catalase and SOD) and broad suppression of pulmonary pro-oxidants (NADPH oxidases and iNOS), via promotion of nuclear Nrf2 levels. Correspondingly, metabolomics was employed understand altered pulmonary metabolism and the protective effects of artesunate in allergic asthma. Liquid and gas chromatography mass spectrometry (LC/MS & GC/MS) were employed to investigate bronchoalveolar lavage fluid and serum of experimental allergic asthma with artesunate treatment. Our results reveal that artesunate can reverse disease-associated metabolite ...
Without an effective vaccine for the prevention of malaria, a fundamental component of the strategy for the control of this disease is based on prompt and effective treatment. Due to the high resistance level of Plasmodium falciparum to the most affordable drugs such as chloroquine and sulfadoxine-pyrimethamine, artemisinin-based combination therapies are presently used in many countries or are being developed for registration. One artemisinin combination therapy that is drawing a certain degree of interest is the combination of artesunate (a short half-life drug) plus amodiaquine (a long half-life drug that is presently used in loose combination in many countries). The short half-life drug achieves substantial and rapid parasite killing, while a high concentration of the long half-life drug kills off the remaining malaria parasites. In addition to the effectiveness of 3 days of treatment (rapid clearance of fever and malaria parasites) in western and central Africa, where resistance to ...
The National Institute of Malariology, Parasitology, and Entomology conducted this study as part of routine surveillance on drug efficacy following the 2009 World Health Organization protocol (2). After obtaining written consent, patients (age of inclusion, 2-60 years) were enrolled and given dihydroartemisinin/piperaquine (Pharbaco, Hanoi, Vietnam) at a target dosage of 2.4 mg/kg for dihydroartemisinin and 18 mg/kg for piperaquine once a day for 3 days. Patients with treatment failures were subsequently given quinine hydrochlorate (30 mg/kg/d) and doxycycline (3 mg/kg/d) for 7 days. Primary endpoint was adequate clinical and parasitologic response (ACPR) on day 42; PCR genotyping, comparing day 0 and day of failure samples, was used to distinguish recrudescence from reinfection with another strain (2). Dried blood spots were collected on day 0 and analyzed for mutations in the K13 propeller domain (3), Pfmdr1 copy number (4), and Pfplasmepsin2 (PfPM2) copy number (5), which are markers ...
A constant struggle between the search for new drug formulations and evolving drug-resistant parasites has marked the history of antimalarial medicine. Resistance to chloroquine has rendered the drug ineffective for instance in many parts of the world. Therapies that combine artemisinin derivatives with other companion drugs are currently being focused on by anti-malaria experts. Artemisinin-based combination therapy (ACT) is what these combinations are called. Acting quickly in the bloodstream, artemisinins help the patient feel better faster and clear away the parasites rapidly. By reducing the number of gametocytes - the infective version of the parasite - in the bloodstream, they may also help reduce transmission of the disease. ACT has few known side effects. Theres little documented resistance to artemisinins, and their combination with other drugs may slow resistance to these companion drugs as well. The bad thing about these combination drugs is that they are more expensive than the ...
ABSTRACT: BACKGROUND: Artemisinin-based combination therapies (ACT) are widely used in African countries, including Cameroon. Between 2005 and 2007, five randomized studies comparing different treatment arms among artesunate-amodiaquine and other ACT were conducted in Cameroonian children aged two to 60 months who had uncomplicated Plasmodium falciparum malaria. In these studies, the categorical criterion proposed by the World Health Organization (WHO) to assess the relative effectiveness of anti- malarial drugs, was repeatedly evaluated on Days 14, 21 and 28 after treatment initiation. The aim of the present study was to compare the effects of different treatments on this repeated ordinal outcome, hence using the fully available information. METHODS: The quantitative synthesis was based on individual patient data. Due to the incomplete block design concerning treatment arms between different trials, a mixed treatment comparison (MTC) meta-analysis approach was adopted. The repeated ordinal outcome was
The purpose of this thesis is to investigate the therapeutic potential of artesunate, an anti-malaria drug, on allergy and allergic asthma. Firstly, we studied the anti-inflammatory effects of artesunate on allergic asthma by employing a murine asthma model. In this study, female Balb/c mice were actively sensitized and challenged by ovalbumin to induce airway inflammation, mucus hypersecretion and airway hyperresponsiveness. Artesunate (3, 10, 30 mg/kg, given intraperitoneally) markly inhibited OVA-induced increases in total cell counts and eosinophil counts and IL-4, IL-5, IL-13 and eotaxin levels in bronchoalveolar lavage fluid in a dose dependent manner. Artesunate also substantially (P,0.05) reduced serum levels of OVA-IgE and IgG1; whereas the levels of OVA-specific IgG2a were not significantly affected. In addition, artesunate was shown to restore the levels of Th1 related cytokines such as IFN-gamma and IL-12 back to basal level in a dose dependent manner. Histological analysis further ...
|jats:sec||jats:title|Summary|/jats:title||jats:p|Multiple alleles at the |jats:italic|kelch13|/jats:italic| locus conferring artemisinin resistance (ART-R) are currently spreading through malaria parasite populations in Southeast Asia, providing a unique opportunity to directly observe an ongoing soft selective sweep, to investigate why resistance alleles have evolved multiple times and to determine fundamental population genetic parameters for Plasmodium. We sequenced the |jats:italic|kelch13|/jats:italic| gene (n=1,876), genotyped 75 flanking SNPs, and measured clearance rate (n=3,552) in parasite infections from Western Thailand (2001-2014). We describe 32 independent coding mutations: these included common mutations outside the |jats:italic|kelch13|/jats:italic| propeller region associated with significant reductions in clearance rate. Mutations were first observed in 2003 and rose to 90% by 2014, consistent with a selection coefficient of ~0.079. There was no change in diversity in flanking
<p>An outline of the opportunities and challenges in large-scale use of artemisinin combination therapies to treat malaria.</p>
BACKGROUND: Use of different methods for assessing the efficacy of artemisinin-based combination antimalarial treatments (ACTs) will result in different estimates being reported, with implications for changes in treatment policy. METHODS: Data from different in vivo studies of ACT treatment of uncomplicated falciparum malaria were combined in a single database. Efficacy at day 28 corrected by PCR genotyping was estimated using four methods. In the first two methods, failure rates were calculated as proportions with either (1a) reinfections excluded from the analysis (standard WHO per-protocol analysis) or (1b) reinfections considered as treatment successes. In the second two methods, failure rates were estimated using the Kaplan-Meier product limit formula using either (2a) WHO (2001) definitions of failure, or (2b) failure defined using parasitological criteria only. RESULTS: Data analysed represented 2926 patients from 17 studies in nine African countries. Three ACTs were studied: ...
Best practices, policy and innovations in the administration of healthcare in developing communities and countries. For administrators, academics, researchers and policy leaders. Includes peer reviewed research papers. Edited by Dr. Judith Shamian, President of the International Council of Nurses, Geneva CH
The emergence of resistance to the artemisinin drug, a potent anti-malarial medicine, now threatens to affect the big gains achieved in recent years in reducing the global burden of malaria - an estimated 1.2 billion fewer malaria cases and 6.2 million fewer malaria deaths globally between 2001 and 2015. This resistance, to artemisinin, becomes all…
We describe an analysis of genome variation in 825 P. falciparum samples from Asia and Africa that identifies an unusual pattern of parasite population structure at the epicenter of artemisinin resistance in western Cambodia. Within this relatively small geographic area, we have discovered several distinct but apparently sympatric parasite subpopulations with extremely high levels of genetic differentiation. Of particular interest are three subpopulations, all associated with clinical resistance to artemisinin, which have skewed allele frequency spectra and high levels of haplotype homozygosity, indicative of founder effects and recent population expansion. We provide a catalog of SNPs that show high levels of differentiation in the artemisinin-resistant subpopulations, including codon variants in transporter proteins and DNA mismatch repair proteins. These data provide a population-level genetic framework for investigating the biological origins of artemisinin resistance and for defining ...
Artemisinin combinations hold great promise for tackling malaria, but they must be used prudently to ensure they are sustainable for decades to come, says <EM>Ramanan Laxminarayan.</EM>
Articles that is. The spread of resistance to artemisinin drugs, the main-stay of modern Plasmodium falciparum (and even P. vivax in some places) malaria therapy, would endanger control programs globally (previously discussed here, here, here, and here). Last week saw a series of high-profile publications which received an impressive amount of coverage in the general…
Dihydroartemisinin (DHA), the main active metabolite of artemisinin derivatives strongly inhibits human papillomavirus-induced tumor formation.
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WANG PHA, Thailand-Dr. Aung Pyae Phyo hasnt seen a malaria case in five days. Thats not so unusual anymore at the clinic he runs in this small town j ...
those artemisinins again... Hi, Lisa; I dont know exactly how these things work, and the best source of info I have found to date is the review...
Most donor agencies only procure drugs approved by a Stringent Regulatory Authority or the World Health Organization (WHO) Prequalification Programme in an effort to ensure high quality. This study compares the quality of artemisinin-based combination therapies (ACTs) produced by WHO-approved manufacturers with non-approved manufacturers and suggests policy changes to improve quality of donor-procured drugs. The results of this study suggest that ACTs produced by WHO-approved manufacturers perform nearly five times better than those of non-approved manufacturers, but some approved ACTs have too little active pharmaceutical ingredient. The US Presidents Malaria Initiative tests every batch of every drug it procures before distribution to recipient countries. Other donors should follow suit to ensure that drugs purchased with taxpayer dollars are of the highest quality.. [The official response to this article from the World Health Organization Prequalification of Medicines Programme was published ...
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This study describes the outcome of 25 travellers with severe malaria who returned from malaria-endemic regions and were treated at 7 centres in Europe with intravenous artesunate. Among these 25 patients, one child and 24 adults (mean ± SD age 44.1 ± 16.1 years), 10 patients received the dosing regimen for artesunate initially recommended by WHO and 11 received artesunate, 2.4 mg/kg/dose. ...
This study describes the outcome of 25 travellers with severe malaria who returned from malaria-endemic regions and were treated at 7 centres in Europe with intravenous artesunate. Among these 25 patients, one child and 24 adults (mean ± SD age 44.1 ± 16.1 years), 10 patients received the dosing regimen for artesunate initially recommended by WHO and 11 received artesunate, 2.4 mg/kg/dose. ...
Data for artesunate, used for the treatment of malaria, indicates IVC in conjunction with IV Artesunate makes a substantial difference in advanced cancers.
Find out how to take Artesunate (drug) and its dose. Describes the best time to take the drug and precautions if any that should be followed.
[100 Pages Report] Check for Discount on United States Artemisinin Market Report 2021 report by QYResearch Group. Notes: Sales, means the sales volume of Artemisinin Revenue, means...
rtemisinin SOD™ combines pure artemisinin for immune support, green tea extract to promote healthy levels of SOD (superoxide dismutase), curcumin and quercetin for their healthy impact on inflammation and resulting inhibitory affect on NF...
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The efficacy and safety of artemether-lumefantrine for the treatment of malaria in nonimmune populations are not well defined. In this study, 165 nonimmune patients from Europe and non-malarious areas of Colombia with acute, uncomplicated falciparum malaria or mixed infection including P. falciparum were treated with the six-dose regimen of artemether-lumefantrine. The parasitologic cure rate at 28 days was 96.0% for the per protocol population (119/124 patients). Median times to parasite clearance and fever clearance were 41.5 and 36.8 hours, respectively. No patient had gametocytes after Day 7. Treatment was well tolerated; most adverse events were mild to moderate and seemed to be related to malaria. There were few serious adverse events, none of which were considered to be drug-related. No significant effects on ECG or laboratory parameters were observed. In conclusion, the six-dose regimen of artemether-lumefantrine was effective and well tolerated in the treatment of acute uncomplicated falciparum
This study evaluated and compared the efficacy of five brands of Artemisinin Combination Therapies (ACTs); Dihydroartemisinin plus Piperaquine, Artesunate plus Amodiaquine, Artesunate plus Sulphadoxine/Pyrimethamine, Artemether plus lumefantrine and Artesunate plus mefloquine combinations in vivo in P.berghei infected swiss albino mice. The experimental animals were pre-screened to rule out infection. All drugs were administered as clinical doses for the curative test and the Mean Percentage Parasitemia level assessed daily for seven days and on day 60. The results showed that all the drugs were effective with artesunate plus amodiaquine combination being the most efficacious followed by dihydroartemisinin plus piperaquine and artesunate plus sulphadoxine plus pyrimethamine combinations followed by artesunate plus mefloquine combination and artemether plus lumefantrine combination which was the least efficacious. Results on day 60 showed increasing parasitemia levels in mice which received Artemether
Abstract. The emergence of artemisinin-resistant Plasmodium falciparum in the Greater Mekong Subregion threatens both the efficacy of artemisinin-based combination therapy (ACT), the first-line treatment for malaria, and prospects for malaria elimination. Monitoring of ACT efficacy is essential for ensuring timely updates to elimination policies and treatment recommendations. In 2014-2015, we assessed the therapeutic efficacies of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) for the treatment of uncomplicated P. falciparum at three study sites in Rakhine, Shan, and Kachin states in Myanmar. Patients presenting with uncomplicated P. falciparum malaria were enrolled, treated, and followed up for 28 days for AL or 42 days for DP. Both AL and DP demonstrated good therapeutic efficacy at all three study sites. The 28-day cure rate for AL was > 96% across all study sites, and the 42-day cure rate for DP was 100%. Parasitemia on day 3 was detected in 0%, 3.3%, and 3.6% of
BACKGROUND: The emergence of resistance against artemisinin combination treatment is a major concern for malaria control. ACTs are recommended as the rescue treatment, however, there is limited evidence as to whether treatment and re-treatment with ACTs select for drug-resistant P. falciparum parasites. Thus, the purpose of the present study is to investigate the impact of (re-)treatment using artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) on the selection of P. falciparum multidrug resistance-1 (Pfmdr1) alleles in clinical settings.. METHODS: P. falciparum positive samples were collected from children aged 12-59 months in a clinical trial in DR Congo and Uganda. Pfmdr1 single nucleotide polymorphisms (SNPs) analysis at codons N86Y, Y184F, and D1246Y were performed at baseline and post-treatment with either AL or ASAQ as a rescue treatment using nested PCR followed by restriction fragment length polymorphism (RFLP) assays.. RESULTS: The pre-treatment prevalence of Pfmdr1 N86 and ...
Introduction: Artesunate is a semi-synthetic derivative of artemisinin, a natural compound from the herb sweet wormwood (Artemisia annua L). Artemisinin has been used for centuries in traditional Chinese medicine while artesunate has recently been used as an anti-malarial drug. Artesunate is also cytotoxic to human cancer cells. Since the use of artesunate as an anti-malarial agent is associated with few adverse effects, artesunate may represent a less toxic alternative to conventional chemotherapy. This study investigates the effects of artesunate on ovarian cancer cell lines and the mechanism(s) underlying its activity. Methods and Results: Artesunate had a time- and dose-dependent growth inhibitory effect on all ovarian carcinoma cell lines examined (SKOV3, OVCAR3, IG-OV-1, HEY) using an MTT assay. Further examination of artesunate-treated SKOV3 and HEY cells using Oregon Green-488 and Annexin-V-FLUOS/propidium iodide staining indicated that artesunate had a strong anti-proliferative effect ...
We report a large multicenter genome-wide association study of Plasmodium falciparum resistance to artemisinin, the frontline antimalarial drug. Across 15 locations in Southeast Asia, we identified at least 20 mutations in kelch13 (PF3D7_1343700) affecting the encoded propeller and BTB/POZ domains, which were associated with a slow parasite clearance rate after treatment with artemisinin derivatives. Nonsynonymous polymorphisms in fd (ferredoxin), arps10 (apicoplast ribosomal protein S10), mdr2 (multidrug resistance protein 2) and crt (chloroquine resistance transporter) also showed strong associations with artemisinin resistance. Analysis of the fine structure of the parasite population showed that the fd, arps10, mdr2 and crt polymorphisms are markers of a genetic background on which kelch13 mutations are particularly likely to arise and that they correlate with the contemporary geographical boundaries and population frequencies of artemisinin resistance. These findings indicate that the risk of new
Artemisinin and its derivatives provide faster clearance of parasitemia than any other antimalarial drugs and these drugs are part of frontline combination therapies in areas where drug-resistant Plasmodium falciparum exists. Clinical resistance to artemisinins is emerging on the Thailand-Cambodia border, making it imperative to investigate mechanisms of artemisinin resistance. Previous work in our laboratory showed ring-stage parasites enter a dormant state after exposure to artemisinin. We hypothesize that this period of dormancy is directly related to recrudescence and prolonged parasite clearance times in patients, and possibly resistance. The target of artemisinin is currently unknown, and potential resistance mechanisms are not well described. Our laboratory previously selected artemisinin resistance in P. falciparum clones D6 (Africa), W2 (southeast Asia), and a patient isolate from Thailand, TM91c235. Studies were attempted in order to characterize artemisinin resistant phenotypes and ...
Artemisinin and its derivatives provide faster clearance of parasitemia than any other antimalarial drugs and these drugs are part of frontline combination therapies in areas where drug-resistant Plasmodium falciparum exists. Clinical resistance to artemisinins is emerging on the Thailand-Cambodia border, making it imperative to investigate mechanisms of artemisinin resistance. Previous work in our laboratory showed ring-stage parasites enter a dormant state after exposure to artemisinin. We hypothesize that this period of dormancy is directly related to recrudescence and prolonged parasite clearance times in patients, and possibly resistance. The target of artemisinin is currently unknown, and potential resistance mechanisms are not well described. Our laboratory previously selected artemisinin resistance in P. falciparum clones D6 (Africa), W2 (southeast Asia), and a patient isolate from Thailand, TM91c235. Studies were attempted in order to characterize artemisinin resistant phenotypes and molecular
Artemisinin-based combination therapy (ACT) is recommended as a means of prolonging the effectiveness of first-line malaria treatment regimens. Different brands of mefloquine (MQ) have been reported to be non-bioequivalent; this could result in sub-therapeutic levels of mefloquine with decreased efficacy. In 2002, mefloquine-artesunate (MQ-AS) combination therapy was adopted as the first-line treatment for uncomplicated Plasmodium falciparum malaria in the Amazon region of Peru. Although MQ resistance has yet to be reported from the Peruvian Amazon, it has been reported from other countries in the Amazon Region. Therefore, continuous monitoring is warranted to ensure that the first-line therapy remains efficacious. This study examines the in vivo efficacy and pharmacokinetic parameters through Day 56 of three commercial formulations of MQ (Lariam®, Mephaquin®, and Mefloquina-AC® Farma) given in combination with artesunate ...
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The combined gametocidal effect of primaquine plus artemisinin-combination therapy (ACT) to reduce post-treatment transmission of P. falciparum malaria is a key operational research question for malaria treatment (previously discussed here). And the evidence of adding primaquine, particularly in areas of low to medium transmission, keeps piling up. Smithius et al. report results from a massive…
Resistance to malaria drugs can be found at varying levels and low levels of resistance may not impact on control. Artemisinin and its derivatives, are not used alone for the treatment of uncomplicated malaria, but are combined with a partner drug; this is known as artemisinin-based combination therapy (ACT). Currently the level of artemisinin resistance means that ACT treatment can still be effective in these areas provided the partner drug is efficacious. However, there is a real and serious risk that drug resistance will worsen and spread further. ACT resistance has already been identified on the Thai-Cambodia border. Intense efforts by the global malaria control community are underway to attempt to halt the spread of these resistant parasites and to delay emergence of resistance elsewhere ...
The study was conducted in southern Zambia, with colleagues from the Johns Hopkins Malaria Research Institute in Macha. Researchers analyzed data from surveys conducted in 2007 and between 2008 and 2009. In both surveys, households were screened for malaria using rapid diagnostic tests and treated with artemisinin combination therapy when malaria was detected.. According to the new study, a proactive test-and-treat case-detection strategy resulted in a sixfold reduction in prevalence in 2008 and 2009, with the initial parasite prevalence at 4 percent. Test and treat showed a twofold reduction in 2007, when community prevalence was higher at 24 percent.. "Proactive case detection with treatment using artemisinin-combination therapy can reduce transmission and provide indirect protection to household members. If resources permit, this strategy could be targeted to hot spots to achieve further reductions in malaria transmission," said William J. Moss, MD, senior author of the study and associate ...
This is probably the first publication on efficacy of AS+SMP in the treatment of uncomplicated falciparum malaria. The high cure rate demonstrated for AS+-SMP (,90%) in this study was expected because of the synergistic effect of artesunate and SMP and potentially because of the non-wide use of SMP as an antimalarial in this country. Previously high efficacy of SMP for the treatment of uncomplicated P. falciparum malaria was reported in other African countries [8-10].. Although the loose combinations of AS+SMP was slightly (not significantly) more efficacious than the fixed one, the fixed regimen of AS+SMP is most promising since it permits reduction of the treatment duration to a maximum of 24 h. The mechanism of action of SM drug is the same as of sulfadoxine(S), but its protein binding and elimination half-life permit the new regimen to be developed in SM rather than in SP [6, 7, 16]. The repeated loading dose of AS is responsible for a drastic destruction of parasites whereas the SMP ...
Abstract Artemisinin resistance in Plasmodium falciparum threatens the remarkable efficacy of artemisinin-based combination therapies worldwide. Thus, greater insight into the resistance mechanism using monitoring tools is essential. The ring-stage survival assay is used for phenotyping artemisinin-resistance or decreased artemisinin sensitivity. Here, we review the progress of this measurement assay and explore its limitations and potential applications ...
A growing public health risk originating in Asia, drug resistance, is threatening to undermine gains in malaria control. Significant progress has been made in recent years in the fight against malaria. Since 2000, mortality from malaria has decreased by over 25 percent globally. Scale-up of effective malaria interventions, including the use of artemisinin-based combination therapies - the most effective drug for treating the disease - have been instrumental to this success. However, growing resistance to artemisinins by the malaria parasite has been emerging in Southeast Asia and is threatening to reverse the gains that have been made to date. In this interview, Senior Technical Officer at Malaria Consortium, Dr Prudence Hamade, explains how dangerous a spread the spread of parasite resistance to anti-malarial drugs could be in Asia and beyond.. Q: Can you explain what drug-resistant malaria is and what the state of resistance is now in Southeast Asia?. A: Drug-resistant malaria refers to the ...
We included 27 trials, enrolling 16,382 adults and children, and conducted between 2002 and 2010. Most trials excluded infants aged less than six months and pregnant women.. DHA-P versus artemether-lumefantrine In Africa, over 28 days follow-up, DHA-P is superior to artemether-lumefantrine at preventing further parasitaemia (PCR-unadjusted treatment failure: RR 0.34, 95% CI 0.30 to 0.39, nine trials, 6200 participants, high quality evidence), and although PCR-adjusted treatment failure was below 5% for both ACTs, it was consistently lower with DHA-P (PCR-adjusted treatment failure: RR 0.42, 95% CI 0.29 to 0.62, nine trials, 5417 participants, high quality evidence). DHA-P has a longer prophylactic effect on new infections which may last for up to 63 days (PCR-unadjusted treatment failure: RR 0.71, 95% CI 0.65 to 0.78, two trials, 3200 participants, high quality evidence).. In Asia and Oceania, no differences have been shown at day 28 (four trials, 1143 participants, moderate quality evidence), ...
The artemisinin compounds, which are well-known for their potent therapeutic antimalarial activity, possess in vivo and in vitro antitumor effects. Although the anticancer effect of artemisinin compounds has been extensively reported, the precise mechanisms underlying its cytotoxicity remain under intensive study. In the present study, a high-throughput quantitative proteomics approach was applied to identify differentially expressed proteins of HCT116 colorectal cancer cell line with artesunate (ART) treatment. Through Ingenuity Pathway Analysis, we discovered that the top-ranked ART-regulated biological pathways are abrogation of fatty acid biosynthetic pathway and mitochondrial dysfunction. Subsequent assays showed that ART inhibits HCT116 cell proliferation through suppressing the fatty acid biosynthetic pathway and activating the mitochondrial apoptosis pathway. In addition, ART also regulates several proteins that are involved in NF-κB pathway, and our subsequent assays showed that ART suppresses
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The parasite that causes malaria is showing signs of resistance to the most potent drugs currently used against it. Scientists report that top-line drugs called
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Eurartesim(R) - dihydroartemisinin piperaquine (DHA-PQP) - the first artemisinin combination therapy (ACT) has been approved by the European Medicines Agency (EMA) for the treatment of uncomplicated malaria.
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Pädiatrische Medikamentenformulierungen sind ein wichtiger Fortschritt in der Therapie von afrikanischen Kindern, die an Malaria tropica erkrankt sind. In dieser klinischen Studie wurde die...
Oxford University scientists have found that the more effective way to beat malaria is to use less effective drugs some of the time: simultaneously using a non-artemisinin therapy amongst more effective artemisinin-based combinations slows the spread of artemisinin-resistant parasites.
As the MDGs transition to the Sustainable Development Goals (SDGs) in 2016, MMVs priorities too are evolving. We will focus less on developing artemisinin combination therapies and more on next-generation antimalarials. These future medicines will break the cycle of relapsing malaria, overcome the challenges of compliance and drug resistance, and protect vulnerable populations. In doing so, they will support the realization of the proposed SDG 3 - to ensure the sustainability of healthy lives and wellbeing for all, at all ages.. And while the goals have yet to be finalised, we, the global health community must advocate for health to feature high on the agenda. Health is after all, the foundation of all sustainable development.. Our goal to break the cycle of malaria and poverty by developing and delivering new medicines is certainly ambitious and MMV is but a small organization of 55 individuals. Yet, thanks to our ever-growing network of partners and donors, who are as committed as MMV to the ...
Antimalarials are drugs which are used for prophylaxis, treatment & prevention of Malaria. They are used for treatment of Malaria in individuals with suspected or confirmed infection and for prevention of infection in individuals visiting a .....
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Under a license from The Hong Kong University of Science and Technology and Hadasit University, Artemis Therapeutics is developing artemisone, a
The TWiP professors solve the case of the Ugandan Child with Splenomegaly, and reveal that mutations in the P. falciparum genome that confer artemisinin resistance interfere with endocytic uptake of hemoglobin.. ...
TY - CONF. T1 - Artesunate targets the Bcl-2 antagonist of cell death promoter in humans. AU - Karuso, P.. AU - Kwon, H. J.. AU - Gotsbacher, M.. AU - Cho, S.. AU - Kim, N. H.. AU - Liu, F.. PY - 2016. Y1 - 2016. M3 - Abstract. SP - 16. EP - 16. ER - ...
Henriques, G; Martinelli, A; Rodrigues, L; Modrzynska, K; Fawcett, R; Houston, DR; Borges, ST; d Alessandro, U; Tinto, H; Karema, C; Hunt, P; Cravo, P (2013) Artemisinin resistance in rodent malaria -
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V&B Catalogue 99, Department of vaccines and other biologicals, English WHO/V&B/99.02 WHO informal consultation on clinical neurological investigations required for patients treated with artemisinin compounds and derivatives, 20 July 1998, English TDR/TDF/99.1 in limited supply ...
A South African regions success in nearly eliminating malaria is the first major example of how the Chinese-inspired drug artemisinin, along with other prevention methods, can help trounce the malaria-causing parasite.
A new study examines whether people newly insured through the Affordable Care Act are adding pressure to primary care access challenges.
Mum-bai: The new tele-com pol-icy in the works should en-sure equal treat-ment for com-pet-ing tech-nolo-gies, an ad-vance yearly road map for spec-trum auc-tions and re-duced levies to im-prove the in-dus-trys health, the Cel-lu-lar Op-er-a-tors As-so-ci-a-tion of In-dia said.. The as-so-ci-a-tions 11-point pro-posal to the Depart-ment of Telecom-mu-ni-ca-tions high-lighted that current li-cens-ing rules un-der an 1885 act are out-dated and need to be over-hauled to in-clude new con-cepts such as net neu-tral-ity, cloud ser-vices and In-ter-net of Things and keep pace with changes in tech-nol-ogy.. "What-sApp can-not of-fer free ser-vices while we are charged. The gov-ern-ment should also es-tab-lish how much of a spec-trum band should be used in the next 3-5 years, keep-ing in mind the rise in con-sumer de-mand," COAI Di-rec-tor Gen-eral Ra-jan Mathews told ET.. The sec-tors fi-nan-cial health can be im-proved if spec-trum us-age charges are re-duced to 1% from 1-5% cur-rently and the ...
Chemotherapy remains an important approach in the fight against malaria. Artemether-lumefantrine combination is widely in use due to its effectiveness against Plasmodium falciparum. Misuse in the form of multiple repeated doses of this anti-malaria drug is rampant in Nigeria. This study was designed to assess the hepatotoxic and clastogenic potential of extreme misuse of artemether-lumefantrine in rats. Graded doses of artemether-lumefantrine (1-5 mg/kg body weight) were administered by oral gavage for 6 weeks, twice daily, for 3 consecutive days per week. Artemether-lumefantrine, at all doses, did not have significant effects on the body and relative liver weight of treated group compared to the negative control group. The mean γ-glutamyltransferase, alanine, and aspartate aminotransaminase activity in groups of artemether-lumefantrine treated rats were significantly higher (p , 0.05) than that of the negative control group indicating that repeated administration of artemether-lumefantrine may ...
Artemether & Lumefantrine - Get up-to-date information on Artemether & Lumefantrine side effects, uses, dosage, overdose, pregnancy, alcohol and more. Learn more about Artemether & Lumefantrine
Background: Chlorproguanil-dapsone-artesunate (CDA) was developed as an affordable, simple, fixed-dose artemisinin-based combination therapy for use in Africa. This trial was a randomized parallel-group, double-blind, double-dummy study to compare CDA and artemether-lumefantrine (AL) efficacy in uncomplicated Plasmodium falciparum malaria and further define the CDA safety profile, particularly its hematological safety in glucose-6-phosphate dehydrogenase (G6PD) -deficient patients. Methods and Findings: The trial was conducted at medical centers at 11 sites in five African countries between June 2006 and August 2007. 1372 patients (≥1 to |15 years|old, median age 3 years) with acute uncomplicated P. falciparum malaria were randomized (2:1) to receive CDA 2/2.5/4 mg/kg once daily for three days (N = 914) or six-doses of AL over three days (N = 458). Non-inferiority of CDA versus AL for efficacy was evaluated in the Day 28 per-protocol (PP) population using parasitological cure (polymerase chain
NutriCology Artemisinin 100mg 90 Capsules Pure artemisinin or Qinghaosu, the active constituent of the herb Artemisia annua (sweet wormwood). Good quality Artemisia annua contains 0.3-0.5% artemisinin, so pure artemisinin provides hundreds of times more of the active constituent artemisinin than the whole herb itself. NutriCology introduced artemisinin to the U.S. market more than a decade ago. NutriCology does independent potency assays on every batch (using HPLC), and independent tests verify its effectiveness. NutriCology artemisinin is minimum 98.5% pure, and does not contain thujone. For more information about quality of artemisinin, see High Quality Artemisinin. Suggested use: As a dietary supplement, 1 or 2 capsules one or two times daily before meals, or as directed by a healthcare practitioner. Artemisinin is best taken as part of a program that includes appropriate liver support nutrients. Sensitive individuals may want to take with food. CAUTION: Not indicated for pregnant or
Malaria Research and Treatment is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies related to all aspects of malaria.
Background: The development and spread of antimalarial drug resistant parasites contributes to the global impact of the disease. In vivo efficacy assessments of treatments for Plasmodium falciparum malaria are essential for ensuring effective case management. Artemisinin-based combinations have been adopted as the first-line treatment for uncomplicated P. falciparum malaria in Cameroon since 2004. Methods: A total of 177 children aged six-months to 10 years with uncomplicated mono-infected falciparum malaria were randomized (1:1) to receive artesunate/sulphadoxine-pyrimethamine (AS/SP) or artesunate/amodiaquine (AS/AQ) pediatric tablets and followed up for 28 days according to the standard World Health Organization in vivo drug efficacy monitoring protocol. The primary and secondary endpoints were PCR uncorrected and corrected cure rates, as measured by adequate clinical and parasitological response (ACPR) on day 28. Results: The PCR corrected cure rate was high, overall (88.1%, 95% CI 83.1-93.1), 85.9%
Artemether-lumefantrine (AL), adopted in Kenya for malaria treatment, remains highly efficacious. However, there are heightened concerns because resistance to Artemisinin combination therapy (ACTs) is now well documented in Southeast Asia (SEA). This resistance is associated with slow parasite clearance rates (CRs). There is now need for more genetically determined artemisinin resistance data from malarious regions that use ACT for malaria treatment. Therefore, the main objective of this study was to determine the role that population genetics plays in Plasmodium falciparum parasites exposed to artemisinin treatment amongst patients taking part in an efficacy clinical trial in Kisumu county, western Kenya. To accomplish this, two sets of archived samples were used. The first set was collected before the introduction of AL (pre- ACTs n= 29) and the second set from a randomized open labeled trial (post-ACTs n= 92). A panel of 12 microsatellites (MS) and 91 single nucleotide polymorphisms (SNPs) ...
Artesunate Plus Sulfadoxine-Pyrimethamine is an artesunate-based oral medication used to treat malaria. It consists of artesunate and sulfadoxine/pyrimethamine. "Artesunate+Sulfadoxine-Pyrimethamine for the Treatment of Uncomplicated Falciparum Malaria (ASPF)". clinicaltrials.gov. University of Oxford. July 11, 2012. Retrieved June 6, 2017 ...
BACKGROUND: Emergence of artemisinin resistance in southeast Asia poses a serious threat to the global control of Plasmodium falciparum malaria. Discovery of the K13 marker has transformed approaches to the monitoring of artemisinin resistance, allowing introduction of molecular surveillance in remote areas through analysis of DNA. We aimed to assess the spread of artemisinin-resistant P falciparum in Myanmar by determining the relative prevalence of P falciparum parasites carrying K13-propeller mutations. METHODS: We did this cross-sectional survey at malaria treatment centres at 55 sites in ten administrative regions in Myanmar, and in relevant border regions in Thailand and Bangladesh, between January, 2013, and September, 2014. K13 sequences from P falciparum infections were obtained mainly by passive case detection. We entered data into two geostatistical models to produce predictive maps of the estimated prevalence of mutations of the K13 propeller region across Myanmar. FINDINGS: Overall, ...
Severe malaria in neonates is a rare occurrence because of the protective effect of fetal haemoglobin and passively acquired maternal antibodies. Despite this protection, severe malaria can still occur and may be confused with neonatal sepsis due to an overlap of clinical manifestations. Therefore, febrile neonates in malaria endemic region should be routinely screened for malaria because any delay in making a diagnosis and instituting adequate and effective treatment can lead to the death of the neonate. This is the first clinical report and successful use of parenteral artesunate for treatment of severe malaria in a Nigerian neonate that is documented in literature to the best of our knowledge.
Detailed Artemether / Lumefantrine dosage information for adults and children. Includes dosages for Malaria; plus renal, liver and dialysis adjustments.
China Kingherbs′ 99% Artemisinin (CAS No.: 63968-64-9), Find details about China Artemisia Annua Extract, Artemisinin from Kingherbs′ 99% Artemisinin (CAS No.: 63968-64-9) - Kingherbs Limited
BACKGROUND: Artemisinin-resistant Plasmodium falciparum malaria parasites are now present across much of mainland Southeast Asia, where ongoing surveys are measuring and mapping their spatial distribution. These efforts require substantial resources. Here we propose a generic smart surveillance methodology to identify optimal candidate sites for future sampling and thus map the distribution of artemisinin resistance most efficiently. METHODS: The approach uses the uncertainty map generated iteratively by a geostatistical model to determine optimal locations for subsequent sampling. RESULTS: The methodology is illustrated using recent data on the prevalence of the K13-propeller polymorphism (a genetic marker of artemisinin resistance) in the Greater Mekong Subregion. CONCLUSION: This methodology, which has broader application to geostatistical mapping in general, could improve the quality and efficiency of drug resistance mapping and thereby guide practical operations to eliminate malaria in affected
HIV infection, and potentially its treatment, increases the risk of an arterial ischemic stroke. Multiple etiologies and lack of clear case definitions inhibit progress in this field. Several etiologies, many treatable, are relevant to HIV-related stroke. To fully understand the mechanisms and the terminology used, a robust classification algorithm to help ascribe the various etiologies is needed. This consensus paper considers the strengths and limitations of current case definitions in the context of HIV infection. The case definitions for the major etiologies in HIV-related strokes were refined (e.g., varicella zoster vasculopathy and antiphospholipid syndrome) and in some instances new case definitions were described (e.g., HIV-associated vasculopathy). These case definitions provided a framework for an algorithm to help assign a final diagnosis, and help classify the subtypes of HIV etiology in ischemic stroke.,br/, OBJECTIVES: An increasing proportion of people living with HIV are older ...
Malaria during pregnancy, particularly Plasmodium falciparum malaria, has been linked to increased morbidity and mortality, which must be reduced by both preventive measures and effective case management. The World Health Organization (WHO) recommend
Early this morning, the New England Journal of Medicine released a piece warning of potential artemisinin-resistant malaria near the Cambodia-Thailand border. Artemisinin is a drug used in combination therapies against malaria. Since the 1990s, when artemisinin-based combination therapies (ACTs) were introduced, there have been significant reductions in malaria cases around the world. Countries began to consider malaria eradication instead of malaria control. In 2006, the World Health Organization (WHO) recommended artemisinin-based therapies as the first line of control against uncomplicated Plasmodium falciparum (a protozoan parasite causing a specific type of malaria) malaria cases in countries where the disease is endemic.. Studies from 2008 and 2009 document the reduced susceptibility to the anti-malarial drug in Plasmodium falciparum, the most lethal among the malaria-causing parasites.. The studies show that some P. falciparum parasites are taking a longer time to die than previously ...
Studies were conducted to determine how malaria parasites are cleared from the blood after antimalarial treatment. Neither artesunate nor quinine decreased parasitized red cell deformability or increased antibody binding. In acute falciparum malaria, ring-infected erythrocyte surface antigen (RESA) was observed in erythrocytes without malaria parasites (RESA-red blood cell [RBC]), indicating prior parasitization. In uncomplicated malaria, RESA-RBC numbers increased significantly (P=.002) within 24 h of starting artesunate but rose much more slowly (7 days) after quinine treatment. In severe malaria, RESA-RBC increased significantly (P=. 001) within hours of starting artesunate but not with quinine treatment (P=.43). RESA-RBCs were not produced after drug treatment of malaria parasite cultures in vitro. Rapid malaria parasite clearance after treatment with artemisinin derivatives results mainly from the extraction of drug-affected parasites from host erythrocytes-presumably by the spleen. This explains
Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited human enzyme defect. This deficiency provides some protection from clinical malaria, but it can also cause haemolysis after administration of drugs with oxidant properties. Methods The safety of chlorproguanil-dapsone+artesunate (CD+A) and amodiaquine+sulphadoxine-pyrimethamine (AQ+SP) for the treatment of uncomplicated P. falciparum malaria was evaluated according to G6PD deficiency in a secondary analysis of an open-label, randomized clinical trial [1]. 702 children, treated with CD+A or AQ+SP and followed for 28 days after treatment were genotyped for G6PD A- deficiency. Findings In the first 4 days following CD+A treatment, mean haematocrit declined on average 1.94% (95% CI 1.54 to 2.33) and 1.05% per day (95% CI 0.95 to 1.15) respectively in patients with G6PD deficiency and normal patients; a mean reduction of 1.3% per day was observed among patients who received AQ+SP regardless of G6PD status (95% CI 1
Emerging resistance to first-line antimalarial combination therapies threatens malaria treatment and the global elimination campaign. Improved therapeutic strategies are required to protect existing drugs and enhance treatment efficacy. We report that the piperazine-containing compound ACT-451840 exhibits single-digit nanomolar inhibition of the Plasmodium falciparum asexual blood stages and transmissible gametocyte forms. Genome sequence analyses of in vitro-derived ACT-451840-resistant parasites revealed single nucleotide polymorphisms in pfmdr1, which encodes a digestive vacuole membrane-bound ATP-binding cassette transporter known to alter P. falciparum susceptibility to multiple first-line antimalarials. CRISPR-Cas9 based gene editing confirmed that PfMDR1 point mutations mediated ACT-451840 resistance. Resistant parasites demonstrated increased susceptibility to the clinical drugs lumefantrine, mefloquine, quinine and amodiaquine. Stage V gametocytes harboring Cas9-introduced pfmdr1 ...
Contents Editorial: The challenge of dengue vaccine development and introduction Jacqueline L. Deen Does increased general schooling protect against HIV infection? A study in four African cities Judith R. Glynn, Michel Caraël, Anne Buvé, Séverin Anagonou Léopold Zekeng, Maina Kahindo,Rosemary Musonda Pregnancy interval and delivery outcome among HIV-seropositive and HIV-seronegative women in Kisumu, Kenya Anna M. Eijk, Kevin M. De Cock, John G. Ayisi, Daniel H. Rosen Juliana A. Otieno, Bernard L. Nahlen, Richard W. Steketee Epidemiological and entomological surveillance of the co-circulation of DEN-1, DEN-2 and DEN-4 viruses in French Guiana Florence Fouque, Romuald Garinci, Pascal Gaborit The efficacy of chloroquine, sulfadoxine-pyrimethamine and a combination of both for the treatment of uncomplicated Plasmodium falciparum malaria in an area of low transmission in western Uganda Richard Ndyomugyenyi, Pascal Magnussen, Siân Clarke Addition of artesunate to chloroquine for treatment of ...
In the past decade, the massive scale-up of insecticide-treated bed nets (ITNs) and indoor residual spraying (IRS), together with the use of artemisinin-based combination treatments, have led to major changes in malaria epidemiology and vector biology. Overall malaria prevalence and incidence have been greatly reduced worldwide [1]. But the reductions in malaria have not been achieved uniformly; some sites have experienced continued reductions in both clinical malaria and overall parasite prevalence [2-6], while other sites showed stability or resurgence in malaria despite high coverage of ITNs and IRS [7-12]. Persistence and resurgence of vector populations continues to be an important issue for malaria control and elimination [12-16]. More importantly, extensive use of ITNs and IRS has created intensive selection pressures for malaria vector insecticide resistance as well as for potential outdoor transmission, which appears to be limiting the success of ITNs and IRS. For example, in Africa, ...
August 2003). "Artemisinins target the SERCA of Plasmodium falciparum". Nature. 424 (6951): 957-61. doi:10.1038/nature01813. ... The main evidence came from a Xenopus oocyte system describing specific interactions between artemisinins and PfATP6 as well as ... A single amino acid residue can determine the sensitivity of SERCAs to artemisinins". Nature Structural & Molecular Biology. 19 ... "A single amino acid residue can determine the sensitivity of SERCAs to artemisinins". Nature Structural & Molecular Biology. 19 ...
... is an artemisinin derivative and the mechanism of action for artemisinins is unknown. One of the proposed mechanisms ... Dellicour S, Hall S, Chandramohan D, Greenwood B (2007). "The safety of artemisinins during pregnancy: a pressing question". ...
Artemisinins can be used alone, but this leads to a high rate of recrudescence (return of parasites) and other drugs are ... Artemisinins are generally well tolerated at the doses used to treat malaria. The side effects from the artemisinin class of ... Artemisinins are not used for malaria prophylaxis (prevention) because of the extremely short activity (half-life) of the drug ... Artemisinins were later found to possess a broad spectrum of activity against a wide range of trematodes, including Schistosoma ...
Keiser, J.; Utzinger, J. R. (2007). "Artemisinins and synthetic trioxolanes in the treatment of helminth infections". Current ...
Artemisinins are sesquiterpene lactones isolated from Artemisia annua, a Chinese traditional medicine. The risk of death from ...
Artesunate is in the class of medications known as artemisinins, which are derivatives from sweet wormwood (Artemisia annua). ... His team, however, demonstrated resistance of Plasmodium falciparum to artemisinins in Western Cambodia. New treatments would ...
Weina, PJ (2008). "Artemisinins from folklore to modern medicine--transforming an herbal extract to life-saving drugs". ... For their high efficacy, safety and stability, artemisinins such as artemether and artesunate became the drugs of choice in ... All clinical trials by this time confirmed that artemisinins are more effective than the conventional antimalarial drugs, such ... directly resulting in the discovery and development of a class of new antimalarial drugs called artemisinins. It was officially ...
Artemisinins and derivatives are proving to be candidates as drugs of choice for trematodiasis. In regions where helminthiasis ...
... evaluation to determine and predict the neurotoxicity of artemisinins". Toxicology. 279 (1-3): 1-9. doi:10.1016/j.tox.2010.09. ...
Clark RL (2012). "Effects of artemisinins on reticulocyte count and relationship to possible embryotoxicity in confirmed and ...
The project resulted in the discovery of artemisinins, a class of antimalarial drugs, from the medicinal plant Artemisia annua ...
4-trioxane ring are important potential improvements over the naturally derived artemisinins. The peroxide group in the 1,2,4- ...
"Rectal artemisinins rapidly eliminate malarial parasites". EurekAlert!. 2008-03-27. Archived from the original on 3 April 2008 ...
Eckstein-Ludwig U, Webb R, Van Goethem I, East J, Lee A, Kimura M, O'Neill P, Bray P, Ward S, Krishna S (2003). "Artemisinins ... CAs to artemisinins". Nat Struct Mol Biol 12 (7): 628-9. doi:10.1038/nsmb947. பப்மெட் 15937493. ...
... artemisinins MeSH D02.455.849.765.424 --- farnesol MeSH D02.455.849.765.444 --- gossypol MeSH D02.455.849.765.750 --- santonin ... artemisinins MeSH D02.389.338.450 --- lipid peroxides MeSH D02.389.338.825 --- tert-butylhydroperoxide MeSH D02.389.338.912 ...
... and it should be used only when artemisinins are not available.[11][12][13][14] Quinine is also used to treat lupus and ...
Prudent use can make artemisinins sustainable. By Ramanan Laxminarayan. Since its introduction in the 1950s, chloroquine has ... But, despite their promise, artemisinins need to be used prudently to ensure that they can be used to treat malaria for decades ... But, despite their promise, artemisinins need to be used prudently to ensure that they can be used to treat malaria for decades ...
Review: Plasmodium sensitivity to artemisinins: magic bullets hit elusive targets February 2, 2011 - 13:53 -- Patrick Sampao. ... Lack of Association of the S769N Mutation in Plasmodium falciparum SERCA (PfATP6) with Resistance to Artemisinins. April 13, ... Artemisinins are proposed to act in the malaria parasite cytosol by oxidizing dihydroflavin cofactors of redox-active ... Artemisinins rapidly oxidize leucomethylene blue (LMB) to methylene blue (MB); they also oxidize dihydroflavins such as the ...
... and artemisinins (ART) with long UTLs. Unfortunately, almost all new targets currently being explored for development of novel ... rational drug design lessons from pleiotropic action of quinolines and artemisinins.. Muregi FW1. ...
Inducing Effect of Dihydroartemisinic Acid in the Biosynthesis of Artemisinins with Cultured Cells of Artemisia annua by ... Jianhua Zhu, Jiazeng Yang, Zihan Zeng, et al., "Inducing Effect of Dihydroartemisinic Acid in the Biosynthesis of Artemisinins ...
Malaria Parasite Showing Signs of Resistance to Top-Line Drugs (Artemisinins). October 29, 2008. By MedNews Leave a Comment ... Scientists report that top-line drugs called artemisinins take nearly twice as long to knock out the parasite in people who ...
In this study, the antiplasmodial activity of SC83288 against artemisinins was profiled in order to assess its potential to ... The results obtained in this study are consistent with artemisinins and SC83288 having distinct modes of action and different ... Based on growth inhibition and ring survival assays, no cross-resistance was observed between artemisinins and SC83288, using ... supports efforts to continue the clinical development of SC83288 against severe malaria as an alternative to artemisinins in ...
西太平洋区域委员会, 060 (马尼拉:世卫组织西太平
Artemisinins-based combination therapies (ACTs) are being recommended against uncomplicated malaria in endemic areas of Africa ... Molecular screening for Plasmodium falciparum resistance markers for artemisinins in Mbita, Kenya. ...
Mechanism of Resistance in Artemisinins. The resistance of plasmodium parasites to artemisinin is attributed to young ring ...
Fully Synthetic Artemisinins. It is important to recall that some limitations of artemisinins such as short half-life (between ... 6. Future Development of Artemisinins as Anticancer Drugs. Artemisinins have been recommended and widely used as antimalarials ... Artemisinins seems to regulate key players participating in multiple pathways such as NF-κB, survivin, NOXA, HIF-1α, and BMI-1 ... The first generation of semisynthetic artemisinins includes arteeter and artemether, the lipophilic artemisinins, whereas ...
Book; Format: print Publisher: Geneva : World Health Organization, 2007Other title: Use of rectal artemisinin-based suppositories in the management of severe malaria.Title translated: Suppositoires à base dαartemisinine : utilisation des suppositoires à base dartémisinine dans la prise en charge du paludisme grave : rapport dune consultation informelle de lOMS..Online access: Full text now in IRIS Availability: Items available for loan: WHO HQ [Call number: WC 770 2007AR] (1). ...
Artemisinins: A class of drugs used for the treatment (not prevention) of malaria usually as a part of a combination therapy, ...
Results of search for su:{Artemisinins} and su-to:Drug resistance. Refine your search. *Availability * Limit to currently ...
Recent researches of antitumor activity of artemisinins on breast cancer mainly focus on the nanoliposomal artemisinins [11, 39 ... indicating that the anticancer activity of artemisinins have selectivity. Artemisinins might cause antitumor activity in cancer ... Deeper investigations showed us that artemisinins also cause immune response to the cancer cells [7, 10, 40]. Five kinds of ... Since then, increasing number of literatures proved the anti-leukemia potentials of artemisinins, detailed in Table 1.. Table 1 ...
Artemisinins. Lumefantrine. Artemether. Piperaquine. Amodiaquine. Artemether-lumefantrine combination. Dihydroartemisinin. ...
Artemisinins. Antimalarials. HIV Protease Inhibitors. Protease Inhibitors. Enzyme Inhibitors. Molecular Mechanisms of ...
Artemisinins. Ivermectin. Antimalarials. Antiprotozoal Agents. Antiparasitic Agents. Anti-Infective Agents. To Top ...
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. ...
... multifaceted resistance to artemisinins. Malar J 15:149. https://doi.org/10.1186/s12936-016-1206-9 CrossRefPubMedPubMedCentral ...
Artemisinins: pharmacological actions beyond anti-malarial. Pharmacol Ther. 2014;142(1):126-39.CrossRefGoogle Scholar ...
From Artemisia annua L. to Artemisinins Product Type: Book. Edition: 1. First Published: 2017 ...
Ring-stage survival assays (RSA) to evaluate the in-vitro and ex-vivo susceptibility of Plasmodium falciparum to artemisinins [ ... Plasmodium falciparum: multifaceted resistance to artemisinins. Malar J. 2016;15:149. DOIPubMed ...
  • Artemisinins are a family of drugs that currently form the frontline treatment against Plasmodium falciparum malaria. (eurekalert.org)
  • Lead researcher Leann Tilley, working with colleagues from Thailand, Singapore and the USA, demonstrates that resistant strains of Plasmodium falciparum sourced from the Pailin region of Cambodia can be made susceptible to artemisinin treatment either through extended drug treatment or through a combination therapy of artemisinins and clinically-used proteasome inhibitors. (medindia.net)
  • Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase) inhibitors effected potent inhibition of proliferation with IC 50 s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase) and a putative kinase inhibitor displayed no activity. (plos.org)
  • In this study, the antiplasmodial activity of SC83288 against artemisinins was profiled in order to assess its potential to replace, or be combined with, artemisinin derivatives. (biomedcentral.com)
  • With the further development of artemisinin and its derivatives, studies have found that artemisinins also have desirable antitumor activity in human cancer treatment. (springer.com)
  • However, the rationale for the use of artemisinins in anticancer therapy must be addressed by a greater understanding of the underlying mechanisms involved in their cytotoxic effects. (hindawi.com)
  • In light of the vast preclinical literature on anticancer properties of artemisinins and their excellent, well-established safety profile it is surprising that there are not more reports, or more widespread off-label use of artemisinins for cancer. (plos.org)
  • Then a team coordinated by Stefan Kubicek, Group Leader at CeMM, eventually got a lead: In their latest study, published in Cell (DOI: 10.1016/j.cell.2016.11.010), they showed that artemisinins hit the bulls eye. (eurekalert.org)
  • With our study, we could show that artemisinins change the epigenetic program of glucagon-producing alpha cells and induce profound alterations of their biochemical function", Stefan Kubicek explains. (eurekalert.org)
  • Obviously, the long term effect of artemisinins needs to be tested," says Stefan Kubicek. (eurekalert.org)
  • His infection did not respond to two kinds of artemisinins but was eventually cleared by quinine, an older drug. (newscientist.com)
  • Inducing Effect of Dihydroartemisinic Acid in the Biosynthesis of Artemisinins with Cultured Cells of Artemisia annua by Enhancing the Expression of Genes," The Scientific World Journal , vol. 2014, Article ID 293190, 7 pages, 2014. (hindawi.com)
  • In xenograft models, exposure to artemisinins substantially reduces tumor volume and progression. (hindawi.com)
  • Artemether is an artemisinin derivative and the mechanism of action for artemisinins is unknown. (wikipedia.org)
  • Because of artemisinins' rapid elimination, they are used in combination with an agent that also kills blood parasites but has a slower elimination rate and a different mechanism of action. (mdedge.com)
  • In close collaboration with research groups at CeMM lead by Christoph Bock and Giulio Superti-Furga as well as the group of Tibor Harkany at the Medical University of Vienna they managed to elucidate the molecular mode of action by which artemisinins reshape alpha cells: The compound binds to a protein called gephyrin, that activates GABA receptors, central switches of the cellular signaling. (eurekalert.org)
  • As the molecular targets for artemisinins in fish, rodents and humans are very similar, chances are high that the effect on alpha cells will also occur in humans. (eurekalert.org)
  • A considerable motivation for the interest in artemisinins in additional indications is their excellent, well-established safety profile. (plos.org)
  • 2.Artemisinins - adverse effects. (who.int)
  • By considering the benefits, limitations, and current and future development of artemisinins, we can then identify emerging questions and address future research needs in this promising field of cancer drug discovery. (hindawi.com)
  • Artemisinins induce drug metabolism through the activation of the pregnane X receptor (PXR) in vitro. (gu.se)
  • Evaluation of artemisinins for the treatment of acute myeloid leukemia. (osu.edu)
  • In addition, potentiation occurs at sub-optimal concentrations of artemisinins and Cys that on their own have little or no effect on parasite growth. (biomedcentral.com)
  • Cys also dramatically enhances the efficacy and protective effect of artemisinins against cerebral malaria induced by infection with the P. berghei ANKA parasite. (biomedcentral.com)
  • With those cell lines, the researchers at CeMM where now able to test their compound library and found artemisinins to have the same effect as an Arx loss. (eurekalert.org)
  • The ability of Cys to improve the anti-plasmodial activity of different clinically used artemisinins was tested. (biomedcentral.com)
  • Ex vivo experiments, indicate that potentiation of the anti-plasmodial activity of artemisinins by Cys is direct and does not require the presence of host factors. (biomedcentral.com)
  • Nosten says public health officials should use this moment, while artemisinins are still mostly effective, to launch an all-out "war" against malaria. (kuow.org)
  • The expectation among researchers is that this will also happen eventually with artemisinins. (kuow.org)
  • So the big fear is that the same could happen with artemisinins. (wuky.org)
  • Artemisinins are proposed to act in the malaria parasite cytosol by oxidizing dihydroflavin cofactors of redox-active flavoenzymes, and under aerobic conditions by inducing their autoxidation. (malariaworld.org)