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
Hemolytic anemia after treatment of severe malaria with intravenous artesunate has been described in malaria-endemic and non-malaria-endemic countries. However, evidence of hemolytic anemia after treatment of malaria with oral ACTs is limited to 2 case reports. Data from the current prospective study confirm our hypothesis that delayed posttreatment hemolysis also occurs after oral artemisinin treatment and provide insight into its frequency and clinical course. In 40% of the patients in our study with uncomplicated malaria and oral ACT treatment, laboratory signs of hemolysis were detected 2 weeks after therapy. In 5 patients, hemolysis persisted 1 month after treatment. Patients with posttreatment hemolysis showed a larger decrease in Hb levels after treatment than did patients without hemolysis. The intensity of hemolysis was mild compared with that after intravenous artesunate. In many reported cases of PADH after intravenous artesunate, patients received blood transfusions (2,9). In other ...
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 ...
... - Artemisinin (ART) or Qinghaosu is a natural compound possessing superior anti-malarial activity. Although intensive studies have been done in the medicinal chemistry field to understand the structure-effect relationship, the biological actions of artemisinin are poorly understood and controversial. Due to the current lack of a genetic amiable model to address this question, and an accidental finding made more than a decade ago during our initial exploratory efforts that yeast Saccharomyces cerevisiae can be inhibited by artemisinin, we have since been using the bakers yeast as a model to probe the molecular and cellular properties of artemisinin and its derivatives (ARTs) in living cells. ARTs were found to possess potent and specific anti-mitochondrial properties and, to a lesser extent, the ability to generate a relatively general oxidative damage...
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.
Artemisinin resistance in falciparum malaria has emerged in western Cambodia exactly where chloroquine resistance arose 50 years ago. Similarly to the resistance to chloroquine that spread to Africa, the experts are wondering whether artemisinin resistance will spread as widely. In such a case the consequences would be disastrous.. ...
1. Cytochrome P450 enzyme system is the most important contributor to oxidative metabolism of drugs. Modification, and more specifically inhibition, of this system is an important determinant of several drug-drug interactions (DDIs). 2. Effects of the antimalarial agent artemisinin and its structural analogues, artemether, artesunate and dihydroartemisinin, on seven of the major human liver CYP isoforms (CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6 and 3A4) were evaluated using recombinant enzymes (fluorometric assay) and human liver microsomes (LC-MS/MS analysis). Inhibitory potency (IC50) and mechanisms of inhibition were evaluated using nonlinear regression analysis. In vitro-in vivo extrapolation using the [I]/Ki ratio was applied to predict the risk of DDI in vivo. 3. All compounds tested inhibited the enzymatic activity of CYPs, mostly through a mixed type of inhibition, with CYP1A2, 2B6, 2C19 and 3A4 being affected. A high risk of interaction in vivo was predicted if artemisinin is coadministrated ...
Search Indian Artesunate Injection Manufacturers and Suppliers Details - Contact to Artesunate Injection Exporters in India, Artesunate Injection Wholesalers, Artesunate Injection Distributors and Traders from India.
PRISM INDUSTRIES LTD - We are one of the trusted manufacturer, exporter and supplier of Artemether, based in Anand, Gujarat, India Artemether, Artemether Supplier
Artemisinin and its derivatives, artesunate, artemether, and dihydroartemisinin, are the most rapidly acting of all antimalarials
... - Buy Artesunate Injection 60mg, 120mg Online USA, UK. Used To Treat severe malaria. artesunate injection 120mg.
Buy Artesunate 50 mg Online - Order Cheapest Artesunate 50 mg from lifesaverpharma- your most reliable online pharmacy. Avail best price in USA, by your doorsteps. Order Artesunate 50 mg Now!
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 ...
Tablet = Artemether 40mg + Lumefantrine 240mg, Inj 1ml = Artemether 80mg, DS Inj 2ml= Artemether 40mg + Lumefantrine 240mg, Suspension 30ml & 60ml = (Artemether 15mg + Lumefantrine 90mg)/5ml ...
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...
Purchase NutriCology Artemisinin - 200 mg - 90 Capsules from Appalachian Organics. Our goal is to provide healthy, natural, and sustainable options
Acts whose titles are printed in light type are those relating to day-to-day management of agricultural matters, and are generally valid for a limited period.. The titles of all other Acts are printed in bold type and preceded by an asterisk.. ...