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)
A group of SESQUITERPENES and their analogs that contain a peroxide group (PEROXIDES) within an oxepin ring (OXEPINS).
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.
A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics.
Tests that demonstrate the relative effectiveness of chemotherapeutic agents against specific parasites.
A phospholipid-interacting antimalarial drug (ANTIMALARIALS). It is very effective against PLASMODIUM FALCIPARUM with very few side effects.
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.
An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood.
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.
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.
A family of diphenylenemethane derivatives.
A long acting sulfonamide that is used, usually in combination with other drugs, for respiratory, urinary tract, and malarial infections.
One of the FOLIC ACID ANTAGONISTS that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis.
A protozoan parasite that occurs naturally in the macaque. It is similar to PLASMODIUM VIVAX and produces a type of malaria similar to vivax malaria (MALARIA, VIVAX). This species has been found to give rise to both natural and experimental human infections.
A genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are PLASMODIUM FALCIPARUM; PLASMODIUM MALARIAE; PLASMODIUM OVALE, and PLASMODIUM VIVAX. Species causing infection in vertebrates other than man include: PLASMODIUM BERGHEI; PLASMODIUM CHABAUDI; P. vinckei, and PLASMODIUM YOELII in rodents; P. brasilianum, PLASMODIUM CYNOMOLGI; and PLASMODIUM KNOWLESI in monkeys; and PLASMODIUM GALLINACEUM in chickens.
Compounds with two peroxide groups, that is, two pairs of adjacent OXYGEN atoms. They may have activity against PLASMODIUM similar to the ARTEMISININS.
Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.
A biguanide compound which metabolizes in the body to form cycloguanil, an anti-malaria agent.
A 4-aminoquinoline compound with anti-inflammatory properties.
The presence of parasites (especially malarial parasites) in the blood. (Dorland, 27th ed)
The self administration of medication not prescribed by a physician or in a manner not directed by a physician.
A republic in eastern Africa, south of UGANDA and north of MOZAMBIQUE. Its capital is Dar es Salaam. It was formed in 1964 by a merger of the countries of TANGANYIKA and ZANZIBAR.
A protozoan parasite of rodents transmitted by the mosquito Anopheles dureni.
AMINO ALCOHOLS containing the ETHANOLAMINE; (-NH2CH2CHOH) group and its derivatives.
Cells or feeding stage in the life cycle of sporozoan protozoa. In the malarial parasite, the trophozoite develops from the MEROZOITE and then splits into the SCHIZONT. Trophozoites that are left over from cell division can go on to form gametocytes.
A complication of MALARIA, FALCIPARUM characterized by the passage of dark red to black urine.
A group of compounds consisting in part of two rings sharing one atom (usually a carbon) in common.
Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect.
A group of compounds that contain a bivalent O-O group, i.e., the oxygen atoms are univalent. They can either be inorganic or organic in nature. Such compounds release atomic (nascent) oxygen readily. Thus they are strong oxidizing agents and fire hazards when in contact with combustible materials, especially under high-temperature conditions. The chief industrial uses of peroxides are as oxidizing agents, bleaching agents, and initiators of polymerization. (From Hawley's Condensed Chemical Dictionary, 11th ed)
An aminoquinoline that is given by mouth to produce a radical cure and prevent relapse of vivax and ovale malarias following treatment with a blood schizontocide. It has also been used to prevent transmission of falciparum malaria by those returning to areas where there is a potential for re-introduction of malaria. Adverse effects include anemias and GI disturbances. (From Martindale, The Extra Pharmacopeia, 30th ed, p404)
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.
Proteins found in any species of protozoan.
A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa. It inhibits plasmodial heme polymerase. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p970)
A hydroxynaphthoquinone that has antimicrobial activity and is being used in antimalarial protocols.
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)
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
Proteins that contain an iron-porphyrin, or heme, prosthetic group resembling that of hemoglobin. (From Lehninger, Principles of Biochemistry, 1982, p480)
The process of finding chemicals for potential therapeutic use.
Inhibitors of the enzyme, dihydrofolate reductase (TETRAHYDROFOLATE DEHYDROGENASE), which converts dihydrofolate (FH2) to tetrahydrofolate (FH4). They are frequently used in cancer chemotherapy. (From AMA, Drug Evaluations Annual, 1994, p2033)
An abnormal elevation of body temperature, usually as a result of a pathologic process.
Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.
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.
A traditional term for all the activities which a physician or other health care professional normally performs to insure the coordination of the medical services required by a patient. It also, when used in connection with managed care, covers all the activities of evaluating the patient, planning treatment, referral, and follow-up so that care is continuous and comprehensive and payment for the care is obtained. (From Slee & Slee, Health Care Terms, 2nd ed)
Therapy with two or more separate preparations given for a combined effect.
A republic in western Africa, south of NIGER between BENIN and CAMEROON. Its capital is Abuja.
A country in northeastern Africa. The capital is Khartoum.
A republic in eastern Africa, south of ETHIOPIA, west of SOMALIA with TANZANIA to its south, and coastline on the Indian Ocean. Its capital is Nairobi.
A republic in eastern Africa, south of SUDAN and west of KENYA. Its capital is Kampala.
Quinolines substituted in any position by one or more amino groups.
Malaria caused by PLASMODIUM VIVAX. This form of malaria is less severe than MALARIA, FALCIPARUM, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day.
The co-occurrence of pregnancy and parasitic diseases. The parasitic infection may precede or follow FERTILIZATION.
A protozoan parasite that causes vivax malaria (MALARIA, VIVAX). This species is found almost everywhere malaria is endemic and is the only one that has a range extending into the temperate regions.
Solid dosage forms, of varying weight, size, and shape, which may be molded or compressed, and which contain a medicinal substance in pure or diluted form. (Dorland, 28th ed)
The continuous sequence of changes undergone by living organisms during the post-embryonic developmental process, such as metamorphosis in insects and amphibians. This includes the developmental stages of apicomplexans such as the malarial parasite, PLASMODIUM FALCIPARUM.
Formerly known as Siam, this is a Southeast Asian nation at the center of the Indochina peninsula. Bangkok is the capital city.
Simultaneous resistance to several structurally and functionally distinct drugs.
An enzyme of the oxidoreductase class that catalyzes the reaction 7,8-dihyrofolate and NADPH to yield 5,6,7,8-tetrahydrofolate and NADPH+, producing reduced folate for amino acid metabolism, purine ring synthesis, and the formation of deoxythymidine monophosphate. Methotrexate and other folic acid antagonists used as chemotherapeutic drugs act by inhibiting this enzyme. (Dorland, 27th ed) EC
A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins.
The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.
Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.
Decisions, usually developed by government policymakers, for determining present and future objectives pertaining to the health care system.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
The oxygen-carrying proteins of ERYTHROCYTES. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements.
The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.
Deoxyribonucleic acid that makes up the genetic material of protozoa.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
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.
Substances that reduce the growth or reproduction of BACTERIA.
Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.

Malaria prophylaxis using azithromycin: a double-blind, placebo-controlled trial in Irian Jaya, Indonesia. (1/4748)

New drugs are needed for preventing drug-resistant Plasmodium falciparum malaria. The prophylactic efficacy of azithromycin against P. falciparum in malaria-immune Kenyans was 83%. We conducted a double-blind, placebo-controlled trial to determine the prophylactic efficacy of azithromycin against multidrug-resistant P. falciparum malaria and chloroquine-resistant Plasmodium vivax malaria in Indonesian adults with limited immunity. After radical cure therapy, 300 randomized subjects received azithromycin (148 subjects, 750-mg loading dose followed by 250 mg/d), placebo (77), or doxycycline (75, 100 mg/d). The end point was slide-proven parasitemia. There were 58 P. falciparum and 29 P. vivax prophylaxis failures over 20 weeks. Using incidence rates, the protective efficacy of azithromycin relative to placebo was 71.6% (95% confidence interval [CI], 50.3-83.8) against P. falciparum malaria and 98.9% (95% CI, 93.1-99.9) against P. vivax malaria. Corresponding figures for doxycycline were 96.3% (95% CI, 85.4-99.6) and 98% (95% CI, 88.0-99.9), respectively. Daily azithromycin offered excellent protection against P. vivax malaria but modest protection against P. falciparum malaria.  (+info)

8-Aminoquinolines active against blood stage Plasmodium falciparum in vitro inhibit hematin polymerization. (2/4748)

From the Walter Reed Army Institute of Research (WRAIR) inventory, thirteen 8-aminoquinoline analogs of primaquine were selected for screening against a panel of seven Plasmodium falciparum clones and isolates. Six of the 13 8-aminoquinolines had average 50% inhibitory concentrations between 50 and 100 nM against these P. falciparum clones and were thus an order of magnitude more potent than primaquine. However, excluding chloroquine-resistant clones and isolates, these 8-aminoquinolines were all an order of magnitude less potent than chloroquine. None of the 8-aminoquinolines was cross resistant with either chloroquine or mefloquine. In contrast to the inactive primaquine prototype, 8 of the 13 8-aminoquinolines inhibited hematin polymerization more efficiently than did chloroquine. Although alkoxy or aryloxy substituents at position 5 uniquely endowed these 13 8-aminoquinolines with impressive schizontocidal activity, the structural specificity of inhibition of both parasite growth and hematin polymerization was low.  (+info)

Alternative oxidase inhibitors potentiate the activity of atovaquone against Plasmodium falciparum. (3/4748)

Recent evidence suggests that the malaria parasite Plasmodium falciparum utilizes a branched respiratory pathway including both a cytochrome chain and an alternative oxidase. This branched respiratory pathway model has been used as a basis for examining the mechanism of action of two antimalarial agents, atovaquone and proguanil. In polarographic assays, atovaquone immediately reduced the parasite oxygen consumption rate in a concentration-dependent manner. This is consistent with its previously described role as an inhibitor of the cytochrome bc1 complex. Atovaquone maximally inhibited the rate of P. falciparum oxygen consumption by 73% +/- 10%. At all atovaquone concentrations tested, the addition of the alternative oxidase inhibitor, salicylhydroxamic acid, resulted in a further decrease in the rate of parasite oxygen consumption. At the highest concentrations of atovaquone tested, the activities of salicylhydroxamic acid and atovaquone appear to overlap, suggesting that at these concentrations, atovaquone partially inhibits the alternative oxidase as well as the cytochrome chain. Drug interaction studies with atovaquone and salicylhydroxamic acid indicate atovaquone's activity against P. falciparum in vitro is potentiated by this alternative oxidase inhibitor, with a sum fractional inhibitory concentration of 0.6. Propyl gallate, another alternative oxidase inhibitor, also potentiated atovaquone's activity, with a sum fractional inhibitory concentration of 0.7. Proguanil, which potentiates atovaquone activity in vitro and in vivo, had a small effect on parasite oxygen consumption in polarographic assays when used alone or in the presence of atovaquone or salicylhydroxamic acid. This suggests that proguanil does not potentiate atovaquone by direct inhibition of either branch of the parasite respiratory chain.  (+info)

Declining concentrations of dihydroartemisinin in plasma during 5-day oral treatment with artesunate for Falciparum malaria. (4/4748)

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)

Comparison of in vivo and in vitro tests of resistance in patients treated with chloroquine in Yaounde, Cameroon. (5/4748)

The usefulness of an isotopic in vitro assay in the field was evaluated by comparing its results with the therapeutic response determined by the simplified WHO in vivo test in symptomatic Cameroonian patients treated with chloroquine. Of the 117 enrolled patients, 102 (87%) completed the 14-day follow-up, and 95 isolates obtained from these patients (46 children, 49 adults) yielded an interpretable in vitro test. A total of 57 of 95 patients (60%; 28 children and 29 adults) had an adequate clinical response with negative smears (n = 46) or with an asymptomatic parasitaemia (n = 11) on day 7 and/or day 14. The geometric mean 50% inhibitory concentration of the isolates obtained from these patients was 63.3 nmol/l. Late and early treatment failure was observed in 29 (30.5%) and 9 (9.5%) patients, respectively. The geometric mean 50% inhibitory concentrations of the corresponding isolates were 173 nmol/l and 302 nmol/l. Among the patients responding with late and early treatment failure, five isolates and one isolate, respectively, yielded a discordant result (in vivo resistance and in vitro sensitivity). The sensitivity, specificity, and predictive value of the in vitro test to detect chloroquine-sensitive cases was 67%, 84% and 86%, respectively. There was moderate concordance between the in vitro and in vivo tests (kappa value = 0.48). The in vitro assay agrees relatively well with the therapeutic response and excludes several host factors that influence the results of the in vivo test. However, in view of some discordant results, the in vitro test cannot substitute for in vivo data on therapeutic efficacy. The only reliable definition of "resistance" in malaria parasites is based on clinical and parasitological response in symptomatic patients, and the in vivo test provides the standard method to determine drug sensitivity or resistance as well as to guide national drug policies.  (+info)

Intrinsic efficacy of proguanil against falciparum and vivax malaria independent of the metabolite cycloguanil. (6/4748)

Mutations in human CYP2C19 and parasite dihydrofolate reductase (dhfr) genes, related to poor metabolism of proguanil and resistance to cycloguanil, respectively, have both been assumed to be associated with poor antimalarial effect by proguanil. To study this, 95 subjects with uncomplicated Plasmodium falciparum or Plasmodium vivax infections in Vanuatu received proguanil treatment for 3 days (adult relative dose of 300-500 mg/day) and were followed up for 28 days. A similarly high antimalarial efficacy against both infections was observed in 62 patients with CYP2C19-related poor metabolizer genotype and in 33 with extensive metabolizer genotype, even though blood cycloguanil was significantly more often detected in those with extensive metabolizer genotype than in those with poor metabolizer genotype. All 28 P. falciparum isolates had two dhfr mutations (residues 59 and 108), suggesting moderate resistance to cycloguanil. The results suggest that the parent compound proguanil has significant intrinsic efficacy against falciparum and vivax malaria independent of the metabolite cycloguanil.  (+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. (7/4748)

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. (8/4748)

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)

Piperaquine, 1,3-bis-[4-(7-chloroquinolyl-4)-piperazinyl-1]-propane, is an anti-malarial compound belonging to the 4-aminoquinolines, which has received renewed interest in treatment of drug resistant falciparum malaria in artemisinin-based combination therapy with dihydroartemisinin. The impurity profile of this drug product is paid an ever-increasing attention. However, there were few published studies of the complete characterization of related products or impurities in piperaquine phosphate bulk and forced degradation samples. The impurities in piperaquine phosphate bulk drug substance were detected by a newly developed gradient phase HPLC method and identified by TOF-MS and ESI-MS. The structures of impurities were confirmed by NMR. Forced degradation studies were also performed for the stability of piperaquine phosphate bulk drug samples and the specificity of the newly developed HPLC method. In silico toxicological predictions for these piperaquine phosphate related impurities were made by
Coartem® is the combination of artemether and lumefantrine used for the treatment of uncomplicated falciparum malaria 1. This oral combination seems to be well-tolerated and is useful for treatment of multi-drug resistant Plasmodium falciparum. This unique anti-malarial agent combines the fast, but short-acting artemether with a less potent, but longer-acting lumefantrine. Original studies with the combination demonstrated safety and efficacy in adults and children with uncomplicated falciparum malaria. 2,3 Additional studies showed superiority with respect to parasite clearance time versus halofantrine,4 chloroquine5, and mefloquine6. Coartem® also demonstrated a faster reduction in parasite burden after 24-hours versus halofantrine4, chloroquine5 (in adults), chloroquine (in children) 7, and mefloquine6. Various other studies have shown artemether-lumefantrine to have a superior 28-day cure rate, as well as time to fever resolution compared to other antimalarial agents.1 Both components of ...
Project researcher: Dr Ilsa Haeusler, Academic Foundation Doctor Ilsas main project during the AFP was to undertake a systematic literature review to investigate the effects of antimalarial drugs on cardiac adverse events. She wanted to determine whether antimalarial drugs, particularly quinoline antimalarials, caused cardiovascular side effects such as prolongation of the QT interval on the electrocardiogram. The project allowed her to learn the fundamentals of systematic reviewing, particularly in terms of literature search, reference acquisition, database design and analysis. The review was large with many variables having been extracted, so dealing with the volume of data was a key learning point. This was a fantastic opportunity to learn about standardised ways of carrying out a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The question of cardiotoxic effects of antimalarial drugs is very relevant to clinical practice on ...
One of the worlds leading malaria researchers has warned radical action is needed to prevent the further spread of a deadly drug-resistant malaria parasite that has the potential to kill millions.
Synonyms for Antimalarials in Free Thesaurus. Antonyms for Antimalarials. 1 synonym for antimalarial: antimalarial drug. What are synonyms for Antimalarials?
Objectives: The in vitro and in vivo efficacy and drug-drug interactions of the novel semi-synthetic endoperoxide artemisone with standard antimalarials were investigated in order to provide the basis for the selection of the best partner drug. Methods: Antimalarial activity and drug interactions were evaluated in vitro against Plasmodium falciparum by the incorporation of [,sup,3,/sup,H]hypoxanthine. In vivo efficacy and drug interactions were assessed using the standard 4-day Peters test. Results: Artemisone was 10 times more potent than artesunate in vitro against a panel of 12 P. falciparum strains, independent of their susceptibility profile to antimalarial drugs, and consistently 4 to 10 times more potent than artesunate in rodent models against drug-susceptible and primaquine- or sulfadoxine/pyrimethamine-resistant Plasmodium berghei lines and chloroquine- or artemisinin-resistant lines of Plasmodium yoelii. Slight antagonistic trends were found between artemisone and chloroquine, ...
Anti-malarial drug resistance in Kenya prompted two drug policy changes within a decade: sulphadoxine-pyrimethamine (SP) replaced chloroquine (CQ) as the first-line anti-malarial in 1998 and artemether-lumefantrine (AL) replaced SP in 2004. Two cross-sectional studies were conducted to monitor changes in the prevalence of molecular markers of drug resistance over the period in which SP was used as the first-line anti-malarial. The baseline study was carried out from 1999-2000, shortly after implementation of SP, and the follow-up study occurred from 2003-2005, during the transition to AL. Blood was collected from malaria smear-positive, symptomatic patients presenting to outpatient centers in Kisumu, Kenya, during the baseline and follow-up studies. Isolates were genotyped at codons associated with SP and CQ resistance. In vitro IC50 values for antifolates and quinolones were determined for isolates from the follow-up study. The prevalence of isolates containing the pfdhfr N51I/C59R/S108N/pfdhps A437G
BACKGROUND: The World Health Organization (WHO) in 2015 stated atovaquone-proguanil can be used in travellers, and is an option in malaria-endemic areas in combination with artesunate, as an alternative treatment where first-line artemisinin-based combination therapy (ACT) is not available or effective. This review is an update of a Cochrane Review undertaken in 2005. OBJECTIVES: To assess the efficacy and safety of atovaquone-proguanil (alone and in combination with artemisinin drugs) versus other antimalarial drugs for treating uncomplicated Plasmodium falciparum malaria in adults and children. SEARCH METHODS: The date of the last trial search was 30 January 2020. Search locations for published trials included the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, and LILACS. To include recently published and unpublished trials, we also searched, the metaRegister of Controlled Trials and the WHO International Clinical Trials Registry Platform ...
BACKGROUND:Antimalarial efficacy studies in patients with uncomplicated Plasmodium falciparum are confounded by a new infection (a competing risk event) since this event can potentially preclude a recrudescent event (primary endpoint of interest). The current WHO guidelines recommend censoring competing risk events when deriving antimalarial efficacy. We investigated the impact of considering a new infection as a competing risk event on the estimation of antimalarial efficacy in single-armed and comparative drug trials using two simulation studies. METHODS:The first simulation study explored differences in the estimates of treatment failure for areas of varying transmission intensities using the complement of the Kaplan-Meier (K-M) estimate and the Cumulative Incidence Function (CIF). The second simulation study extended this to a comparative drug efficacy trial for comparing the K-M curves using the log-rank test, and Grays k-sample test for comparing the equality of CIFs. RESULTS:The complement of
Background: Malaria remains a disease of devastating global impact, killing more than 800,000 people every year-the vast majority being children under the age of 5. While effective therapies are available, if malaria is to be eradicated a broader range of small molecule therapeutics that are able to target the liver and the transmissible sexual stages are required. These new medicines are needed both to meet the challenge of malaria eradication and to circumvent resistance. Methods and Findings: Little is known about the wider stage-specific activities of current antimalarials that were primarily designed to alleviate symptoms of malaria in the blood stage. To overcome this critical gap, we developed assays to measure activity of antimalarials against all life stages of malaria parasites, using a diverse set of human and nonhuman parasite species, including male gamete production (exflagellation) in Plasmodium falciparum, ookinete development in P. berghei, oocyst development in P. berghei and ...
The largest genome-wide association study to date of the malaria parasite Plasmodium falciparum unveils a complex genetic architecture that enables the parasite to develop resistance to our most effective antimalarial drug, artemisinin. The results could help to improve early detection of emerging artemisinin resistance.
For the first time in Africa, researchers said Wednesday they have detected a malaria parasite that is partially resistant to the top anti-malaria drug, artemisinin, raising concern about efforts to fight a disease that ...
Apr 08, 2020 (Reporthive Research via COMTEX) -- Chicago, United States, 2020 -Anti-malarial Drugs Market report covers detailed analysis of industry share, growth factors, development trends, size, major manufacturers and 2025 forecast. The report also analyses innovative business strategies, value added factors and business opportunities. The Anti-malarial Drugs Market reports offers important insights which help the industry experts, product managers, CEOs, and business executives to draft their policies on various parameters including expansion, acquisition, and new product launch as well as analyzing and understanding the market trends. Get a Sample PDF Report @ Global Anti-malarial Drugs industry market professional research 2014-2024, is a report which provides the details about industry overview, industry chain, market size (sales, revenue, and growth rate), gross margin, major manufacturers, development trends and forecast. Key players ...
For centuries, quinoline has been an effective compound in antimalarial drugs, although no one knew its mode of action in vivo. Today, a team led by the Weizmann Institute has discovered its mechanism in infected red blood cells in near-native conditions, by using the ESRF, Alba Synchrotron and BESSY. They publish their results in PNAS.…
DUO-COTECXIN/8T,Antimalarials,Products,NEWZADD2014011500067,Used in the treatment of uncomplicated falciparum malaria and vivax malaria.
Resistance to front-line antimalarials (artemisinin combination therapies) is spreading, and development of new drug treatment strategies to rapidly kill Plasmodium spp. malaria parasites is urgently needed. Azithromycin is a clinically used macrolide antibiotic proposed as a partner drug for combination therapy in malaria, which has also been tested as monotherapy. However, its slow-killing delayed-death activity against the parasites apicoplast organelle and suboptimal activity as monotherapy limit its application as a potential malaria treatment. Here, we explore a panel of azithromycin analogues and demonstrate that chemical modifications can be used to greatly improve the speed and potency of antimalarial action. Investigation of 84 azithromycin analogues revealed nanomolar quick-killing potency directed against the very earliest stage of parasite development within red blood cells. Indeed, the best analogue exhibited 1600-fold higher potency than azithromycin with less than 48 hrs treatment in
A mistake as small as neglecting antimalarials can spoil your holidays completely for you. Here is why antimalarials should be considered before travelling.
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Australian researchers say they have found the key to a new anti-malarial drug, which kills the parasite with a salt overdose. Its the first discovery in the fight against malaria in 20 years.
Using whole-genome analysis and chemogenomics, scientists have discovered novel antimalarial drug targets and drug-resistance genes. The researchers analyzed |250 Plasmodium falciparum cell lines, which were resistant to 37 different anti-malarial compounds.
Manuel Llinás of Pennsylvania State University in the U.S. will characterize the 400 candidate anti-malarial compounds in the so-called Malaria Box by mass spectrometry to help select those likely to be the most effective drugs for clinical development. The Malaria Box is a collection of compounds that display some anti- parasitic activity, but how they work and whether they would make valuable new anti-malarial drugs are unknown. They will analyze red blood cells infected with the malarial parasite P. falciparum to identify the metabolic pathways that are altered by each compound from the Malaria Box. In Phase I, in work while at Princeton University, they determined the metabolic profiles induced by eighty compounds, and discovered that many affected the same pathway. In Phase II, they will analyze the remaining compounds, and expand their approach to determine the metabolic effects of candidate anti-malarial drugs during different stages of parasite development, and upon infection by other ...
Angira, C.H., Otieno, O.A., Muga, R.O. and Abongo, B.O. (2010) Factors Contributing to Antimalarial Drug Resistance in Rachonyo District, Kenya. East African Journal of Public Health, 7, 11-15.
Malaria can be regarded as one of the worlds worst health problems and its incidence is rising inexorably. It already accounts for the deaths of approximately three children every minute. This situation is exacerbated by the increased frequency of parasite resistance to current antimalarial agents and necessitates the development of new drugs to combat this disease P. falciparum possesses a plastid-like organelle, termed the apicoplast, which contains a small, highly reduced 35kb genome encoding tRNA, DNA polymerases and ribosomal proteins. Nuclear proteins are targeted to the apicoplast using clearly defined N-terminal signal and target peptide sequences. This led to the discovery that the apicoplast may be the site of at least two anabolic pathways isoprenoid synthesis and Type II fatty acid synthesis (FAS). This system is also present in bacteria and plants and differs significantly from the Type I FAS system found in humans. This makes the pathway an attractive target for novel ...
Drug-resistant malaria parasites have spread to border regions of Southeast Asia, seriously threatening global efforts to control and eliminate the mosquito-borne disease, researchers say.
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Exploration of Scaffolds from Natural Products with Antiplasmodial Activities, Currently Registered Antimalarial Drugs and Public Malarial Screen Data. . 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.
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 .....
Antimalarial drugs are used for the treatment and prevention of malaria infection. Most antimalarial drugs target the erythrocytic stage of malaria infection, which is the phase of infection that causes symptomatic illness (). The extent of preerythr
Background The use of illegal drugs is seen as a major social problem. The social costs can be high. Methods Self-report data from interviews at intake to the National Treatment Outcome Research Study NTORS for 1075 drug users and cost data from various sources were used to estimate criminal behaviour and health and addiction service costs for...
A team of researchers at the Indian Institute of Science and the Tata Institute of Fundamental Research, both in India, has found that the
An international team of scientists, led by researchers from the Department of Pediatrics at the University of California, San Diego School of Medicine, have identified the first reported inhibitors of a key enzyme involved in survival of the parasite responsible for malaria. Their findings, which may provide the basis for anti-malarial drug development, are currently published in the online version of the Journal of Medicinal Chemistry.
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 ...
Author(s): Renslo, Adam; Mott, BT; Eastman, RT; Guha, R; Sherlach, KS; Siriwardana, A; Shinn, P; McKnight, C; Michael, S; Lacerda-Queiroz, N; Patel, PR | Abstract: Drug resistance in Plasmodium parasites is a constant threat. Novel therapeutics, especially new drug combinations, must be identified at a faster rate. In response to the urgent need for new antimalarial drug combinations we screened a large collection of
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Project details Malaria is a devastating disease that causes 450,000 deaths annually. No new class of antimalarial drug has entered the market in the last 15 years resulting in the emergence of resistance against all clinically used drug classes. Therefore, there is an urgent need to develop new antimalarial clinical candidate drugs.
Novartis International AG / 300 million child-friendly antimalarial treatments supplied without profit by Novartis . Processed and transmitted by NASDAQ OMX Corporate Solutions. The issuer is solely responsible for the content of this announcement.
This blog chronicles the research of the UsefulChem project in the Bradley lab at Drexel University. The main project currently involves the synthesis of novel anti-malarial compounds. The work is done under Open Notebook Science conditions with the actual detailed lab notebook located at More general comments posted here relate to Open Science, especially when associated with chemistry.. ...
This blog chronicles the research of the UsefulChem project in the Bradley lab at Drexel University. The main project currently involves the synthesis of novel anti-malarial compounds. The work is done under Open Notebook Science conditions with the actual detailed lab notebook located at More general comments posted here relate to Open Science, especially when associated with chemistry.. ...
Malaria is more common and severe in pregnant women, increasing their risk of miscarriage and other adverse outcomes. The adverse consequences of malaria in
In the current age of drug resistance, antimalarial choices are inadequate. In order to support the recent eradication agenda, new generations of both chemoprop...
We want to judiciously use antimicrobial and antimalarials only on the people that really need them. So I think a low cost diagnostic test that you could disseminate more widely would allow us to preserve our antimalarials only for the children who need them which would let them work longer ...
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Artefenomel (OZ439) is a synthetic antimalarial agent with the artemisinin pharmacophore. Artefenomel (OZ439) is a long-acting artemisinin-related agent. - Mechanism of Action & Protocol.
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
Artemisinin-based combination therapies (ACTs) are the treatment of choice for uncomplicated Plasmodium falciparum malaria in malaria endemic countries. ACT resistance has already been documented in the main, but not solely in Asia,1 therefore therapeutic alternatives should be investigated. As there are no new drugs at advance stages in the pipeline, current focus should be on novel combinations of existing drugs. This prospective randomised study compares the effectiveness of three antimalaria combination drugs-two well-established combination drugs (artesunate-amodiaquine (AA) and atovaquone-proguanil (AP)) and one … ...
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 ...
Background: Recent studies suggest that antimalarials have antineoplastic properties.. Objective: To investigate whether antimalarials decrease the risk of cancer in systemic lupus erythematosus (SLE).. Methods: An observational prospective cohort study was carried out. 235 patients were included in the study at the time of diagnosis (American College of Rheumatology criteria). The end point was the diagnosis of cancer. Kaplan-Meier cancer-free survival curves for patients treated and not treated with antimalarials were compared. A Cox proportional hazards model was fitted, with cancer as the dependent variable. Age at diagnosis, gender, treatment with azathioprine, cyclophosphamide and methotrexate, smoking, Systemic Lupus International Collaborating Clinics (SLICC) Damage Index 6 months after diagnosis, year of diagnosis and treatment with antimalarials were entered as independent variables.. Results: 209 (89%) patients were women. 233 (99%) patients were white. Mean (SD) age at diagnosis was ...
The impact of vector control measures on the evolution of antimalarial drug resistance is an important issue for malaria control programs. We investigated whether the in vivo efficacy of chloroquine (CQ) in children aged 6-59 months with uncomplicated malaria differed in 9 villages that had benefited from long-term use of insecticide-treated curtains (ITCs) and in 9 nearby non-ITC villages. We also compared the prevalence of genetic markers of resistance to CQ and sulfadoxine-pyrimethamine (SP) between the two groups of villages. The study enrolled 1,035 children with uncomplicated malaria and 231 infected but asymptomatic children. After taking account of re-infections, the proportions of children who experienced clinical failure after treatment with CQ were 14% and 19% in ITC and non-ITC villages, respectively (OR = 0.68; 95% CI: 0.39, 1.18). Parasitologic failure was observed in 49% of children in ITC villages and 58% of children in non-ITC villages (OR = 0.71 95%CI: 0.44, 1.13). The ...
Citation: Lee, S-E., Kim, M-R., Kim, J-H., Takeoka, G.R., Kim, T-W., Park, B-S. 2008. Antimalarial Activity of Anthothecol Derived from Khaya anthotheca (Meliaceae). Phytomedicine 15:533-535. Interpretive Summary: Malaria is a serious disease affecting more than 500 million people worldwide every year. Recent estimates of the global malaria burden have shown increasing levels of malaria morbidity and mortality. The main factor contributing to the increasing malaria mortality and morbidity is the widespread resistance of Plasmodium falciparum to conventional antimalarial drugs such as chloroquine, sulfadoxine-pyrimethamine (SP) and amodiaquine. Since the parasites resistance to medicines continues to undermine malaria control efforts, new antimalarial agents are needed. Anthothecol, a limonoid of Khaya anthotheca (Meliaceae), showed potent antimalarial activity against malaria parasites with IC50 values of 1.4 and 0.17 uM using two different assays. Anthothecol might be a useful product for ...
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. ...
Drug resistance of Plasmodium falciparum, the most deadly human malaria parasite, is a major factor in the widespread persistence of malaria (Ouellette & Kunding 1997, Macreadi et al. 2000). Current efforts focus on research into novel compounds and on measures to prevent or delay resistance once new drugs are introduced. However, malaria therapy has generally not taken into consideration the stage-specificity of action of different drugs. This is an important consideration, since inappropriate timing of administration of antimalarial drugs might limit drug efficacy and favor the selection of drug-resistant parasites.. Few studies have focused on the in vitro stage-specific efficacy of antimalarial compounds (Chimanuka et al. 2001). Most in vitro studies monitoring resistance and susceptibility to antimalarial compounds have been performed by microscopy and by uptake of a radiolabelled nucleic acid precursor 3[H]-hypoxanthine (Desjardins et al. 1979). They are poorly suited to discriminate ...
The World Health Organization (WHO) has developed guidelines for in vivo antimalarial drug efficacy testing for Plasmodium falciparum and Plasmodium vivax in areas with low-to-moderate transmission, such as the Americas. These guidelines are used widely by ministries of health and national malaria control programs to assess the efficacy of their first-line and second-line drugs for the treatment of malaria and to provide the information necessary to update national malaria treatment policies. Following the WHO guidelines, we have conducted in vivo efficacy trials with a variety of drugs and drug combinations against P. falciparum and P. vivax at 13 sites in Peru, Bolivia, and Ecuador. Based on these experiences, we have identified several modifications that we believe should be made in the WHO recommendations to make them more suitable to the relatively low levels of P. falciparum transmission in the Americas and to the logistic challenges of carrying out such studies in sparsely populated areas, such
Malaria, caused by the Plasmodium parasite is still a health problem worldwide due to resistance of the pathogen to current anti-malarials. The search for new anti-malarial agents has become more crucial with the emergence of chloroquine-resistant Plasmodium falciparum strains. Protein kinases such as mitogen-activated protein kinase (MAPK), MAPK kinase, cyclin-dependent kinase (CDK) and glycogen synthase kinase- 3(GSK-3) of parasitic protozoa are potential drug targets. GSK-3 is an enzyme that plays a vital role in multiple cellular processes, and has been linked to pathogenesis of several diseases such as type II diabetes and Alzheimers disease. In the present study, the antiplasmodial property of LiCl, a known GSK-3 inhibitor, was evaluated in vivo for its antimalarial effect against mice infected with Plasmodium berghei. Infected ICR mice were intraperitoneally administered with LiCl for four consecutive days before (prophylactic test) and after (suppressive test) inoculation of P. ...
Plasmodium falciparum, the most deadly agent of malaria, displays a wide variety of resistance mechanisms in the field. The ability of antimalarial compounds in development to overcome these must therefore be carefully evaluated to ensure uncompromised activity against real-life parasites. We report here on the selection and phenotypic as well as genotypic characterization of a panel of sensitive and multidrug-resistant P. falciparum strains that can be used to optimally identify and deconvolute the cross-resistance signals from an extended panel of investigational antimalarials. As a case study, the effectiveness of the selected panel of strains was demonstrated using the 1,2,4-oxadiazole series, a newly identified antimalarial series of compounds with in vitro activity against P. falciparum at nanomolar concentrations. This series of compounds was to be found inactive against several multidrug-resistant strains, and the deconvolution of this signal implicated pfcrt, the genetic determinant of ...
R. McGready (1,2,3), J. Tarning (2), N. Lindegardh (2,3), E.A. Ashley (1,2,3), M. Pimanpanarak (1), B. Kamanikom (2), A. Annerberg (2), P. Singhasivanon (2), N.J. White (2,3), F. Nosten (1,2,3). (1) Shoklo Malaria Research Unit, Mae Sot, Thailand; (2) Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand; (3) Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, UK.. Objectives: The fixed combination of artemether and lumefantrine (co-artemether) is today the most widely used co-formulated artemisinin-based antimalarial combination therapy manufactured to GMP standards. Pregnancy was recently shown to be associated with reduced plasma concentrations of both artemether and lumefantrine in a detailed pharmacokinetic study of thirteen pregnant women with falciparum malaria [1]. The main objective of this study was to determine the population pharmacokinetic properties of lumefantrine in pregnant women with uncomplicated multi-drug resistant falciparum malaria in ...
BioAssay record AID 158533 submitted by ChEMBL: In vitro antiplasmodial activity against chloroquine-sensitive Plasmodium falciparum Haiti 135.
A one day symposium on Antimalarials: Current Approaches and New Directions is being organized jointly by Medicines for Malaria Venture (MMV) and Open Source Drug Discovery malaria (OSDDm) at CSIR-Central Drug Research Institute, Lucknow on 16th November, 2011. This is an effort to apprise the principal investigators joining the OSDDm platform of the latest developments in the design and discovery of new antimalarials. The conference will include lectures by Prof. Stephen Ward, Walter Myers Professor of Parasitology and Deputy Director at Liverpool School of Tropical Medicine and Dr. Jeremy Burrows, Head of Discovery at MMV, Switzerland besides eminent medicinal chemists and biochemists from India working in the area of development of chemotherapy for malaria. ...
To establish the role of the ferrocenyl moiety in the antiplasmodial activity of ferroquine, compounds in which this moiety is replaced by the corresponding ruthenium-based moieties were synthesized and evaluated. In both the sensitive (D 10) and resistant (K1) strains of Plasmodium falciparum, ruthenoquine analogues showed comparable potency to ferroquine. This suggests that a probable role of the ferrocenyl fragment is to serve simply as a hydrophobic spacer group. In addition, ferroquine analogues with different aromatic substituents were synthesized and evaluated. Unexpectedly high activity for quinoline compounds lacking the 7-chloro substituent suggests the ferrocenyl moiety may have an additive and/or synergistic effect. (c) 2007 Elsevier Ltd. All rights reserved.. ...
TY - JOUR. T1 - Synergestic in vitro antimalarial activity of omeprazole and quinine. AU - Skinner-Adams, T.. AU - Davis, Timothy. PY - 1999. Y1 - 1999. M3 - Article. VL - 43. SP - 1304. EP - 1306. JO - Antimicrobial Agents and Chemotherapy. JF - Antimicrobial Agents and Chemotherapy. SN - 0066-4804. IS - 5. ER - ...
Significant interest has been placed on the utility of PK parameters in predicting the treatment response. Most attention has been placed on the correlates of the AUC, as AUC represents both the duration and the degree of exposure. The accurate measurement of AUC in field studies is difficult, so recent efforts for studying the PKs of artemisinin partner drugs have focused on single day 7 drug levels (34). The rationale for this approach is that by day 7 the remaining parasites will be exposed only to the partner drug, as the rapidly eliminated artemisinin derivatives are no longer present. The level of partner drug in the days following dosing may be critical for determining both the clearance of the infection and the potential selection of drug-resistant parasites. Importantly, for the longer-acting partner drugs, the day 7 levels appear to correlate with the AUC (5), as seen for both DEAQ and LR in our study. Several studies from Thailand have examined the relationship between the day 7 ...
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In this article, the in vivo antimalarial activity of novel naphthoquine derivatives is assessed revealing promising candidates for further research.
Mechanistic within-host models integrating blood anti-malarial drug concentrations with the parasite-time profile provide a valuable decision tool for determining dosing regimens for anti-malarial treatments, as well as a formative component of population-level drug resistance models. We reviewed published anti-malarial pharmacokinetic-pharmacodynamic models to identify the challenges for these complex models where parameter estimation from clinical field data is limited. The inclusion of key pharmacodynamic processes in the mechanistic structure adopted varies considerably. These include the life cycle of the parasite within the red blood cell, the action of the anti-malarial on a specific stage of the life cycle, and the reduction in parasite growth associated with immunity. With regard to estimation of the pharmacodynamic parameters, the majority of studies simply compared descriptive summaries of the simulated outputs to published observations of host and parasite responses from clinical ...
Malaria drug discovery is a challenging and difficult task due to the unavailability of the vaccine and lack of newer drugs. The most potent artemisinin and its derivatives, widely used in combination therapies for curing malaria worldwide are also now falling to resistance in some parts of the world. Thus, to combat malaria, new drugs possessing high therapeutic value, minimal toxicity, rapid efficacy and low cost are urgently needed. In this chapter, we will provide an integrated overview on the challenges and opportunities in malaria drug discovery with more emphasis on synthesis of peroxidic antimalarials.
In 2010, malaria killed an estimated 655,000 people worldwide, but some estimates put the death toll at over one million. Since 2006 Artemesinin has been regarded as a miracle cure for malaria because it has few side-effects and, up to now, has been almost 100 per cent effective. Resistance to it was first detected in western Cambodia in 2009, and despite efforts to contain the spread, it appears that it has now spread 800km along Thailands north-western border with Burma.. Concerns have been raised as, twice before, resistance to the then gold standard anti-malarial drugs - chloroquine and sulfadoxine-pyrimethamine - started in the same region before spreading to South-east Asia and Africa, leading to the deaths of millions of children.. Prof Nosten added: We have now seen the emergence of malaria resistant to our best drugs ...
BACKGROUND: Regular anti-malarial therapy in pregnancy, a pillar of malaria control, may affect malaria immunity, with therapeutic implications in regions of reducing transmission. METHODS: Plasma antibodies to leading vaccine candidate merozoite antigens and opsonizing antibodies to endothelial-binding and placental-binding infected erythrocytes were quantified in pregnant Melanesian women receiving sulfadoxine-pyrimethamine (SP) with chloroquine taken once, or three courses of SP with azithromycin. RESULTS: Malaria prevalence was low. Between enrolment and delivery, antibodies to recombinant antigens declined in both groups (p < 0.0001). In contrast, median levels of opsonizing antibodies did not change, although levels for some individuals changed significantly. In multivariate analysis, the malaria prevention regimen did not influence antibody levels. CONCLUSION: Different preventive anti-malarial chemotherapy regimens used during pregnancy had limited impact on malarial-immunity in a ...
TY - JOUR. T1 - Structure-activity relationship of antiparasitic and cytotoxic indoloquinoline alkaloids, and their tricyclic and bicyclic analogues. AU - Van Baelen, Gitte. AU - Hostyn, Steven. AU - Dhooghe, Liene. AU - Tapolcsányi, P.. AU - Mátyus, P.. AU - Lemière, Guy. AU - Dommisse, Roger. AU - Kaiser, Marcel. AU - Brun, Reto. AU - Cos, Paul. AU - Maes, Louis. AU - Hajós, G.. AU - Riedl, Z.. AU - Nagy, Ildikó. AU - Maes, Bert U W. AU - Pieters, Luc. PY - 2009/10/15. Y1 - 2009/10/15. N2 - Based on the indoloquinoline alkaloids cryptolepine (1), neocryptolepine (2), isocryptolepine (3) and isoneocryptolepine (4), used as lead compounds for new antimalarial agents, a series of tricyclic and bicyclic analogues, including carbolines, azaindoles, pyrroloquinolines and pyrroloisoquinolines was synthesized and biologically evaluated. None of the bicyclic compounds was significantly active against the chloroquine-resistant strain Plasmodium falciparum K1, in contrast to the tricyclic ...
In the past, malaria control efforts in sub-Saharan Africa have relied on a combination of vector control with effective treatment using chloroquine. With increasing resistance to chloroquine, attention has now turned to alternative treatment strategies to replace this failing drug. Some countries have already changed their official first-line treatment to sulfadoxine-pyrimethamine, while others are contemplating a switch to artemisinin-based combination treatments (ACTs). Although there are strong theoretical arguments in favor of switching to ACTs, the validity of these arguments in the face of financial constraints has not been previously analyzed. In this report, we use a bioeconomic model of malaria transmission and evolution of drug resistance to examine questions of optimal treatment strategy and coverage when drug resistance places an additional constraint on choices available to the policymaker.
|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
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 ...
Malaria, one of the most common vector borne human diseas-es, is a major world health issue. In 2015 alone, more than 200 million people were infected with malaria, out of which, 429,000 died. Even though artemisinin-based combination therapies (ACT) are highly effective at treating malaria infections, novel efforts towards development of vaccines to prevent transmission are still needed. Pfs25, a post-fertilization stage parasite surface antigen, is a leading transmission-blocking vaccine (TBV) candidate. It is postulated that Pfs25 anchors to the cell membrane using a glycosylphosphatidyl-inositol (GPI) linker, which itself possesses proinflammatory properties ...
Malaria remains one of the most significant global public health challenges, with more than 300 million clinical cases worldwide each year. The lack of an effective licensed vaccine and the continual emergence of drug-resistant malaria parasites make the search for new control and prevention strategies more important than ever. Malaria research is a highly collaborative field that depends on the contribution of unique resources, technologies and biological advances. Accessible and timely sharing of these advances through the establishment of new collaborations is vital for their translation into public health impact.. This conference will address fundamental questions of the biology of the malaria parasite, its vector, the (immune) response of the host and the disease that it causes, and will showcase the latest technological approaches. The use of big data and computational approaches to tackle fundamental biological questions will be assessed. This will be the 15th BioMalPar conference at ...
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Scientists at the Kenya Medical Research Institute (Kemri) have come up with a new drug they believe is much safer and superior to Fansidar in the management of malaria among pregnant women.. KEMRI Centre for Global Health Research chief researcher Dr Simon Kariuki described the new drug, known as Dihydroartemisin-piperaquine, as a second-line intervention that has proved effective in treating clinical malaria when compared to Fansidar, the main drug used for malaria treatment across Africa.. Dr Kariuki said to date, the new drug has passed relevant safety tests after proving to be better tolerated and more effective than Fansidar in preventing malaria among pregnant women during recent tests in Kenya and Uganda. More tests and observations are underway at 10 sites in Kenya, Tanzania and Malawi. The WHO now recommends monthly Fansidar doses for pregnant women after findings that the drug does not provide long-term immunity against malaria.. Pregnancy increases womens chances of getting infected ...
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 ...
Resistance to antimalarial medicines is a threat to global efforts to control and eliminate malaria. Protecting the efficacy of the recommended malaria treatments is a top priority for malaria endemic countries and the global malaria community.
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Artemisinin is the frontline fast-acting anti-malarial against P. falciparum. Emergence and spread of resistant parasite in eastern-India poses a threat to national malaria control programs. Therefore, the objective of our study is to evaluate the artesunate-sulfadoxine-pyrimethamine efficacy in Central India. 180 monoclonal P. falciparum-infected patients received standard ASSP therapy during August 2015-January 2017, soon after diagnosis and monitored over next 42-days. Artemisinin-resistance was assessed through in-vivo parasite clearance half-life (PC1/2), ex-vivo ring-stage survivability (RSA), and genome analysis of kelch13 and other candidate gene (pfcrt, pfmdr1, pfatpase 6, pfdhfr and pfdhps). ...

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