Academic literature on the topic 'Malaria drug treatment][Mefloquine'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'Malaria drug treatment][Mefloquine.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Journal articles on the topic "Malaria drug treatment][Mefloquine"
1
TRIPATHI, RENU, SWAROOP KUMAR PANDEY, and AMBER RIZVI. "Clarithromycin, a cytochrome P450 inhibitor, can reverse mefloquine resistance in Plasmodium yoelii nigeriensis- infected Swiss mice." Parasitology 138, no. 9 (July 15, 2011): 1069–76. http://dx.doi.org/10.1017/s0031182011000850.
Full textAbstract:
SUMMARYDuring the last 2 decades there have been numerous reports of the emergence of mefloquine resistance in Southeast Asia and nearly 50% resistance is reported in Thailand. A World Health Organization report (2001) considers mefloquine as an important component of ACT (artesunate+mefloquine) which is the first line of treatment for the control of uncomplicated/multi-drug resistant (MDR) Plasmodium falciparum malaria. In view of the emergence of resistance towards this drug, it is proposed to develop new drug combinations to prolong the protective life of this drug. Prior studies have suggested that mefloquine resistance can be overcome by a variety of agents such as ketoconazole, cyproheptadine, penfluridol, Icajine and NP30. The present investigation reports that clarithromycin (CLTR), a new macrolide, being a potent inhibitor of Cyt. P450 3A4, can exert significant resistance reversal action against mefloquine resistance of plasmodia. Experiments were carried out to find out the curative dose of CLTR against multi-drug resistant P. yoelii nigeriensis. Mefloquine (MFQ) and clarithromycin (CLTR) combinations have been used for the treatment of this MDR parasite. Different dose combinations of these two drugs were given to the infected mice on day 0 (prophylactic) and day 1 with established infection (therapeutic) to see the combined effect of these combinations against the MDR malaria infection. With a dose of 32 mg/kg MFQ and 225 mg/kg CLTR, 100% cure was observed, while in single drug groups, treated with MFQ or CLTR, the cure was zero and 40% respectively. Therapeutically, MFQ and CLTR combinations 32+300 mg/kg doses cleared the established parasitaemia on day 10. Single treatment with MFQ or CLTR showed considerable suppression of parasitaemia on day 14 but neither was curative. Follow-up of therapeutically treated mice showed enhanced anti-malarial action as reflected by their 100% clearance of parasitaemia. The present study reveals that CLTR is a useful antibiotic to be used as companion drug with mefloquine in order to overcome mefloquine resistance in plasmodia.
2
Nasveld, Peter E., Michael D. Edstein, Mark Reid, Leonard Brennan, Ivor E. Harris, Scott J. Kitchener, Peter A. Leggat, et al. "Randomized, Double-Blind Study of the Safety, Tolerability, and Efficacy of Tafenoquine versus Mefloquine for Malaria Prophylaxis in Nonimmune Subjects." Antimicrobial Agents and Chemotherapy 54, no. 2 (December 7, 2009): 792–98. http://dx.doi.org/10.1128/aac.00354-09.
Full textAbstract:
ABSTRACT This study represents the first phase III trial of the safety, tolerability, and effectiveness of tafenoquine for malaria prophylaxis. In a randomized (3:1), double-blinded study, Australian soldiers received weekly malaria prophylaxis with 200 mg tafenoquine (492 subjects) or 250 mg mefloquine (162 subjects) for 6 months on a peacekeeping deployment to East Timor. After returning to Australia, tafenoquine-receiving subjects received a placebo and mefloquine-receiving subjects received 30 mg primaquine daily for 14 days. There were no clinically significant differences between hematological and biochemical parameters of the treatment groups. Treatment-related adverse events for the two groups were similar (tafenoquine, 13.4%; mefloquine, 11.7%). Three subjects on tafenoquine (0.6%) and none on mefloquine discontinued prophylaxis because of possible drug-related adverse events. No diagnoses of malaria occurred for either group during deployment, but 4 cases (0.9%) and 1 case (0.7%) of Plasmodium vivax infection occurred among the tafenoquine and mefloquine groups, respectively, up to 20 weeks after discontinuation of medication. In a subset of subjects recruited for detailed safety assessments, treatment-related mild vortex keratopathy was detected in 93% (69 of 74) of tafenoquine subjects but none of the 21 mefloquine subjects. The vortex keratopathy was not associated with any effect on visual acuity and was fully resolved in all subjects by 1 year. Tafenoquine appears to be safe and well tolerated as malaria prophylaxis. Although the volunteers' precise exposure to malaria could not be proven in this study, tafenoquine appears to be a highly efficacious drug for malaria prophylaxis.
3
HOSHEN, M. B., W. D. STEIN, and H. GINSBURG. "Mathematical modelling of malaria chemotherapy: combining artesunate and mefloquine." Parasitology 124, no. 1 (January 2002): 9–15. http://dx.doi.org/10.1017/s0031182001008952.
Full textAbstract:
Clinical data on the use of artesunate combined with mefloquine in a variety of treatment regimens and parasite loads in Thailand were modelled on the basis of experimentally determined pharmacokinetic data. The model assumed no pharmacodynamic interaction between artesunate and mefloquine, but that the parasites were already resistant to mefloquine. Predictions of the model accorded well with the data. In particular, in accordance with clinical observations, the model showed that monotherapy with either drug failed to cure at moderate parasitaemia, yet such patients could be treated effectively with the combination of 3 days of artesunate + mefloquine. For high levels of parasitaemia, 5 days of artesunate+mefloquine were needed. Simulations were also performed for situations of lower resistance to mefloquine and for the immune human populations found in Africa. The importance of mathematical modelling of combination therapy is borne out by this study and suggests its wider application for other drug combinations.
4
Nakazawa, Shusuke, Takashi Maoka, Haruki Uemura, Yoshihiro Ito, and Hiroji Kanbara. "Malaria Parasites Giving Rise to Recrudescence In Vitro." Antimicrobial Agents and Chemotherapy 46, no. 4 (April 2002): 958–65. http://dx.doi.org/10.1128/aac.46.4.958-965.2002.
Full textAbstract:
ABSTRACT Recrudescences were simulated in vitro with drug treatment to examine how drug-sensitive parasites survive the treatment. Various numbers of cultured parasites were treated with lethal doses of pyrimethamine or mefloquine for various lengths of time. Recrudescences were observed in parasite populations with larger initial numbers of parasites when the treatment duration was prolonged. Equal numbers of parasitized erythrocytes were treated with various concentrations of pyrimethamine or mefloquine. There was no clear linear relationship between the incidence of recrudescence and the drug concentration. Parasites that had recrudesced were continuously allowed to recrudesce in the succeeding recrudescence experiments. Both the duration from the cessation of treatment to the time at which the recrudescent parasitemia level reached 1% and the growth rate of recrudescent parasites were equal among these recrudescences. The recrudescent parasites in these experiments were as sensitive to the drugs as the parasites tested before treatment were. These results suggest that a parasite culture may contain parasites in some phases that are not killed by drug for up to 10 days, which explains the recrudescences that occur even after treatment.
5
Price, R. N., F. Nosten, C. Luxemburger, M. van Vugt, L. Phaipun, T. Chongsuphajaisiddhi, and N. J. White. "Artesunate/mefloquine treatment of multi-drug resistant falciparum malaria." Transactions of the Royal Society of Tropical Medicine and Hygiene 91, no. 5 (September 1997): 574–77. http://dx.doi.org/10.1016/s0035-9203(97)90032-8.
Full text
6
Sukhai, Mahadeo A., Xiaoming Li, Rose Hurren, Xiaoming Wang, Skrtic Marko, Hong Sun, Marcela Gronda, et al. "The Anti-Malarial Mefloquine Demonstrates Preclinical Activity In Leukemia and Myeloma, and Is Dependent Upon Toll-Like Receptor Signaling for Its Cytotoxicity." Blood 116, no. 21 (November 19, 2010): 290. http://dx.doi.org/10.1182/blood.v116.21.290.290.
Full textAbstract:
Abstract Abstract 290 Known drugs with previously unrecognized anti-cancer activity can be rapidly repurposed for this new indication, given their prior safety and toxicity testing. To identify such compounds, we compiled and screened an in-house library of on-patent and off-patent drugs and screened them to identify agents cytotoxic to hematologic malignancies. From this screen, we identified mefloquine, a quinoline licensed for malaria treatment and prophylaxis. In secondary assays, leukemia and myeloma cell lines were treated with mefloquine for 72 hours and cell viability measured by MTS. Mefloquine decreased the viability of 10/10 human and murine leukemia (LD50 <8.0 μM) and 9/9 human myeloma (LD50 <5.0 μM) cell lines; cell death was confirmed by Annexin V staining. Mefloquine also reduced the viability of 6/6 primary AML samples with LD50 < 5 μ M. These concentrations of mefloquine appear pharmacologically achievable based on prior studies conducted in the context of malaria treatment. In contrast to the effects on malignant cells, mefloquine was significantly less cytotoxic to normal hematopoietic cells (LD50 31.83 ± 5.38 μM) and murine monocyte-derived dendritic cells (LD50 17.56 ± 2.69 μM), Given its in vitro activity, we evaluated the effects of oral mefloquine in mouse xenograft models of leukemia and myeloma. Sublethally irradiated SCID mice were injected subcutaneously with OCI-AML2 or K562 human leukemia cells, MDAY-D2 murine leukemia cells, or LP1 human myeloma cells, and treated with 50 mg/kg mefloquine, or vehicle alone, by gavage. Oral mefloquine delayed tumor growth by up to 60% in all 4 mouse models without toxicity at doses that appear pharmacologically relevant to humans based on scaling for body surface area. Mefloquine's mechanism of action as an anti-malarial agent is unknown. Therefore, to determine the mechanism by which mefloquine induced cell death in malignant cells, we performed gene expression oligonucleotide array analysis of mefloquine-treated OCI-AML2 cells. At times preceding cell death, mefloquine altered the expression of genes associated with Toll-like receptor (TLR) signaling. For example, we detected 4.5-fold up-regulation of STAT1 and >10-fold up-regulation of its downstream targets, including OAS1, IFIT3 and TRIM22, by 24 hr after treatment. Upregulation of additional TLR targets IRF1, IRF7 and IL-8 was also noted by 8 hours after treatment. Mefloquine also induced early activation of NF-κB with a 2.5± 0.2-fold increase noted after 1 hr, using an ELISA-based DNA binding assay. In contrast to TLR activation in malignant cells, changes in TLR targets were not detected in mefloquine-resistant normal dendritic cells, suggesting that mefloquine's effects on TLR signaling were specific to malignant cells. We next investigated whether TLR activation was functionally important for mefloquine's cytotoxicity in malignant cells. STAT1 activity was required for mefloquine-mediated cell death, as U4A bladder sarcoma cells lacking JAK1 were resistant to mefloquine (LD50 14.6± 4.9 μM), compared to the mefloquine sensitive parental line (LD50 2.3± 0.4 μM). TLR signaling requires the immediate downstream adapter proteins MyD88 and TRIF1. To assess the functional importance of TLR activation for mefloquine induced cell death, we knocked down MyD88 and TRIF1 with siRNA. Double knockdown of MyD88 and TRIF1 completely abrogated mefloquine-induced cell death in K562 leukemia cells at concentrations where control cells exhibited up to 80% loss of viability. TLR signaling and up-regulation of STAT1 can increase reactive oxygen species (ROS) generation. Therefore, we measured ROS generation in leukemia cells after mefloquine treatment. Mefloquine increased ROS production in leukemia cells in a dose-dependent manner within 24 hr. Co-treatment with the ROS scavenger N-Acetyl-L-Cysteine abrogated mefloquine-induced ROS production and cell death. Mefloquine-induced ROS production was also abrogated in MyD88 and TRIF1 double knockdown cells. Our data suggest that the known anti-malarial mefloquine displays preclinical activity in leukemia and myeloma through a mechanism related to TLR activation. Thus, these results highlight TLR activation as a novel therapeutic strategy for the treatment of leukemia and myeloma. Moreover, given its prior toxicology and pharmacology testing, mefloquine could be rapidly advanced into clinical trial for patients with leukemia and myeloma. Disclosures: No relevant conflicts of interest to declare.
7
Datta, Pratyay Pratim, Anju Prasad, Chaitali Pattanayak, Ashok Singh Chouhan, and Parbaty Panda. "Pattern of drug prescription for the treatment of falciparum malaria in a medical college in Eastern India." Asian Journal of Medical Sciences 7, no. 4 (July 4, 2016): 80–83. http://dx.doi.org/10.3126/ajms.v7i4.14614.
Full textAbstract:
Background: Drug prescription pattern for the treatment of falciparum malaria differs widely from place to place; but there is also some intra organizational variation of prescription pattern of anti-malarial drugs for the treatment of falciparum malaria.Aims and Objectives: The present study was planned to study the drug utilization pattern for the treatment of falciparum malaria in a tertiary care teaching hospital in eastern India.Materials and Methods: It was a hospital based study conducted in the department of medicine among the patients admitted with confirmed diagnosis of falciparum malaria. Drugs prescribed, average number of drugs per prescription, percentage of drugs prescribed in generic name, percentage of prescription with co-prescription of antibiotics, percentage of prescription having at least an injection prescribed, percentage of drugs prescribed from essential drug list or formulary and average drug cost per prescription are the parameters studied in this study.Results: Average number of drugs per prescription in the present study was 3.96. Artesunate and Mefloquine were the most common anti-malarial drugs prescribed among study subjects. 22.9% patients received oral Chloroquine as anti-malarial drug. 43.3% prescriptions had antibiotics co-prescribed. Only 16.9% drugs were prescribed in generic name. 85.4% of the prescribed drugs were from essential drug list. Average drug cost per patient was Rs. 282/- with minimum of Rs. 55/- and maximum of Rs. 1750/-.Conclusion: Though Artesunate combination therapy is getting popularized gradually but a sizable proportion of patients (22.9%) were prescribed with oral Chloroquine therapy. Generic prescription of drugs should be encouraged among the physicians. Multi-centric study regarding drug prescription can give a broader picture in changing scenario.Asian Journal of Medical Sciences Vol.7(4) 2016 80-83
8
Sukhai, Mahadeo A., Rose Hurren, Angela Rutledge, Bozena Livak, Xiaoming Wang, Ayesh Seneviratne, Maria Christine Cusimano, et al. "Lysosomal Disruption Selectively Targets Leukemia Cells and Leukemia Stem Cells Through A Mechanism Related to Increased Reactive Oxygen Species Production." Blood 118, no. 21 (November 18, 2011): 61. http://dx.doi.org/10.1182/blood.v118.21.61.61.
Full textAbstract:
Abstract Abstract 61 To identify new therapeutic strategies for AML, we compiled and screened an in-house library of on-patent and off-patent drugs to identify agents cytotoxic to leukemia cells. From this screen, we identified mefloquine, an off-patent drug indicated for the treatment and prophylaxis of malaria. In secondary assays, mefloquine decreased the viability of 9/10 human and murine leukemia cell lines (EC50 3.25–8.0 μM). Moreover, it reduced the viability of 4/5 primary AML samples, but was not cytotoxic to normal hematopoietic cells (EC50>31 μM). Importantly, mefloquine reduced the clonogenic growth of primary AML samples, but not normal hematopoietic cells, and completely inhibited engraftment of primary AML cells into immune deficient mice. Finally, systemic treatment with oral mefloquine (50 mg/kg/day) decreased leukemic burden without evidence of toxicity in 4 mouse models of leukemia, including mice engrafted with primary AML cells. Thus, mefloquine effectively targets leukemic cells, including leukemia stem cells, at concentrations that appear pharmacologically achievable and are not toxic to normal hematopoietic cells. To identify the mechanisms of mefloquine-mediated cell death in AML cells, we performed a binary drug combination screen, hypothesizing that drugs that synergized with mefloquine may share overlapping mechanism of action. From this combination screen of 550 drugs, we identified 18 that reproducibly synergized with mefloquine as measured by the Excess over Bliss additivism score, including 3 members of the artemisinin class of anti-malarials: artemisinin, artesunate and artenimol. Strikingly, 10/18 synergistic compounds, including the artemisinins, were known generators of reactive oxygen species (ROS). Therefore we tested mefloquine's ability to increase ROS in leukemic cells. Mefloquine increased ROS production in leukemia cells in a dose- and time-dependent manner. Co-treatment with ROS scavengers α-tocopherol and N-acetyl-cysteine abrogated mefloquine-induced ROS production and cell death, indicating that ROS production was functionally important for mefloquine-mediated cell death. Moreover, the artemisinins induced ROS as single agents, and synergistically increased ROS when combined with mefloquine. To identify cellular target(s) of mefloquine's anti-leukemic effects, we performed a yeast genome-wide functional screen to identify heterozygous gene deletions that rendered yeast more sensitive to mefloquine. 21/37 genes whose depletion conferred >4-fold sensitivity to mefloquine were associated with function of the yeast vacuole, equivalent to the mammalian lysosome. Consistent with these data, fluorescent confocal microscopy demonstrated that mefloquine and artesunate disrupted lysosomes. Cell death after mefloquine and artesunate treatment was caspase-independent and associated with increased incorporation of monodancylcadaverin in autophagosomes, consistent with the effect of these drugs on the lysosomes. To further explore the anti-leukemic activity of lysosomal disruption, we evaluated the anti-leukemic effects of the known lysosomal disrupter L-leucine-leucine methyl ether (LeuLeuOMe). Similar to mefloquine and artesunate, LeuLeuOMe induced cell death in leukemia cells, increased ROS production, and disrupted the lysosomes. Highlighting the potential clinical utility of lysosomal disrupters for the treatment of leukemia, a patient with relapsed/refractory juvenile myelomonocytic leukemia self-administered artemisinin. The artemisinin cleared the circulating blasts from the circulating blasts and the patient proceeded to allotransplant. Finally, to investigate the basis of leukemic cell hypersensitivity to lysosomal disruption, we assessed lysosomal characteristics of primary AML and normal hematopoietic cells. By gene expression analysis, AML patient samples had higher mRNA levels of the lysosomal cathepsins A, B, C, D, H, L, S and Z, compared to CD34+ normal hematopoietic cells, and cathepsins C, D and Z were significantly over-expressed in the LSC compartment, compared to normal HSCs. In summary, our data demonstrate that lysosomal disruption preferentially targets AML cells and AML stem cells through a mechanism related to increased ROS production. Thus, this work highlights lysosomal disruption as a novel therapeutic strategy for AML. Disclosures: Off Label Use: This study includes a case report of off-label use of the anti-malarial artemisinin in the treatment of a case of juvenile myelomonocytic leukemia.
9
Ramharter, Michael, Matthias Schwab, Ghyslain Mombo-Ngoma, Rella Zoleko Manego, Daisy Akerey-Diop, Arti Basra, Jean-Rodolphe Mackanga, et al. "Population Pharmacokinetics of Mefloquine Intermittent Preventive Treatment for Malaria in Pregnancy in Gabon." Antimicrobial Agents and Chemotherapy 63, no. 2 (November 19, 2018): e01113-18. http://dx.doi.org/10.1128/aac.01113-18.
Full textAbstract:
ABSTRACT Mefloquine was evaluated as an alternative for intermittent preventive treatment of malaria in pregnancy (IPTp) due to increasing resistance against the first-line drug sulfadoxine-pyrimethamine (SP). This study determined the pharmacokinetic characteristics of the mefloquine stereoisomers and the metabolite carboxymefloquine (CMQ) when given as IPTp in pregnant women. Also, the relationship between plasma concentrations of the three analytes and cord samples was evaluated, and potential covariates influencing the pharmacokinetic properties were assessed. A population pharmacokinetic analysis was performed with 264 pregnant women from a randomized controlled trial evaluating a single and a split-dose regimen of two 15-mg/kg mefloquine doses at least 1 month apart versus SP-IPTp. Both enantiomers of mefloquine and its carboxy-metabolite (CMQ), measured in plasma and cord samples, were applied for pharmacokinetic modelling using NONMEM 7.3. Both enantiomers and CMQ were described simultaneously by two-compartment models. In the split-dose group, mefloquine bioavailability was significantly increased by 5%. CMQ induced its own metabolism significantly. Maternal and cord blood concentrations were significantly correlated (r2 = 0.84) at delivery. With the dosing regimens investigated, prophylactic levels are not constantly achieved. A modeling tool for simulation of the pharmacokinetics of alternative mefloquine regimens is presented. This first pharmacokinetic characterization of mefloquine IPTp indicates adequate exposure in both mefloquine regimens; however, concentrations at delivery were below previously suggested threshold levels. Our model can serve as a valuable tool for researchers and clinicians to develop and optimize alternative dosing regimens for IPTp in pregnant women.
10
Quinn, Jane C. "Complex Membrane Channel Blockade: A Unifying Hypothesis for the Prodromal and Acute Neuropsychiatric Sequelae Resulting from Exposure to the Antimalarial Drug Mefloquine." Journal of Parasitology Research 2015 (2015): 1–12. http://dx.doi.org/10.1155/2015/368064.
Full textAbstract:
The alkaloid toxin quinine and its derivative compounds have been used for many centuries as effective medications for the prevention and treatment of malaria. More recently, synthetic derivatives, such as the quinoline derivative mefloquine (bis(trifluoromethyl)-(2-piperidyl)-4-quinolinemethanol), have been widely used to combat disease caused by chloroquine-resistant strains of the malaria parasite,Plasmodium falciparum. However, the parent compound quinine, as well as its more recent counterparts, suffers from an incidence of adverse neuropsychiatric side effects ranging from mild mood disturbances and anxiety to hallucinations, seizures, and psychosis. This review considers how the pharmacology, cellular neurobiology, and membrane channel kinetics of mefloquine could lead to the significant and sometimes life-threatening neurotoxicity associated with mefloquine exposure. A key role for mefloquine blockade of ATP-sensitive potassium channels and connexins in the substantia nigra is considered as a unifying hypothesis for the pathogenesis of severe neuropsychiatric events after mefloquine exposure in humans.
Dissertations / Theses on the topic "Malaria drug treatment][Mefloquine"
1
Karbwang, J. "Clinical pharmacology of mefloquine." Thesis, University of Liverpool, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.234865.
Full text
2
Hien, Tran Tinh. "Anti-malaria drug treatment in Vietnam." Thesis, Open University, 2004. http://oro.open.ac.uk/54199/.
Full textAbstract:
Resistance to antimalarial drugs is increasing nearly everywhere in the tropical world, confounding global attempts to "Roll Back Malaria". Antimalarial treatment with artemisinin, artesunate, or artemether has proved rapidly effective in the treatment of non complicated and complicated malaria and remarkably nontoxic. However there is a number of important questions that still need urgent attention: Should artemisinin be deployed alone or in combination with other antimalarial drugs such mefloquine or other compound (s); which is the best regimen (s); can artemisinin and its derivatives (artesunate or artemether) reduce the mortality in severe malaria and which is the best drug(s); are there important neurotoxic side effects in patients treated with this group of antimalarial drugs. In order to answer those questions a series of studies were conducted in Vietnam and these form the basis of this thesis. The conclusion is: 1) Dihydroartemisinin-piperaquine is an inexpensive, safe, highly efficacious fixeddose antimalarial combination treatment that could make an important contribution to the control of multidrug-resistant fa1ciparum malaria for Vietnan1 and other countries. 2) Artemether is a satisfactory alternative to quinine for the treatment of severe malaria in adults. The rectal administration of artemisinin would obviollsly constitute a useful therapeutic advance, in comparing with parenteral drugs such as artemether and artesunate, particularly in areas where parenteral administration is difficult. 3) The artemisinin derivatives have an acceptable safety profile. 4) Viet Nam has shown that it is possible to "Roll Back Malaria" assuming one has access to good drugs and a willingness to implement change. Those studies have helped to confirm that the qinghaosu (artemisinin) group of drugs is the most important new class of antimalarials developed in the last fifty years.
3
Van, Huyssteen Este. "Efficacy enhancement of the antimalarial drugs, mefloquine and artesunate, with PheroidTM technology / E. van Huyssteen." Thesis, North-West University, 2010. http://hdl.handle.net/10394/5050.
Full textAbstract:
Malaria is currently one of the most imperative parasitic diseases in developing countries. Artesunate has a short half-life, low aqueous solubility and resultant poor and erratic absorption upon oral administration, which translate to low bioavailability. Mefloquine is eliminated slowly with a terminal elimination half-life of approximately 20 days and has neuropsychiatric side effects. Novel drug delivery systems have been utilised to optimise chemotherapy with currently available antimalarial drugs. Pheroid™ technology is a patented drug delivery system which has the ability to capture, transport and deliver pharmaceutical compounds. Pheroid™ technology may play a key role in ensuring effective delivery and enhanced bioavailability of novel antimalarial drugs. The aim of this study was to evaluate the possible efficacy and bioavailability enhancement of the selected antimalarial drugs, artesunate and mefloquine, in combination with Pheroid™ vesicles.
The in vitro efficacy of artesunate and mefloquine co-formulated in the oil phase of Pheroid™ vesicles and entrapped in Pheroid™ vesicles 24 hours after manufacturing were investigated against a 3D7 chloroquine-sensitive strain of Plasmodium falciparum. Parasitemia (%) was quantified with flow cytometry after incubation periods of 48 and 72 hours. Drug sensitivity was expressed as 50% inhibitory concentration (IC50) values. An in vivo bioavailability study with artesunate and mefloquine was also conducted in combination with Pheroid™ vesicles, using a mouse model. A sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to analyse the drug levels. C57 BL6 mice were used during this study. The selected antimalarial drugs were administered at a dose of 20 mg/kg with an oral gavage tube. Blood samples were collected by means of tail bleeding.
The in vitro drug sensitivity assays revealed that artesunate, co-formulated in the oil phase of Pheroid™ vesicles and evaluated after a 48 hour incubation period, decreased the IC50 concentration significantly by 90%. Extending the incubation period to 72 hours decreased the IC50 concentration of artesunate, also co-formulated in the oil phase of Pheroid ™ vesicles significantly by 72%. No statistically significant differences between the reference and Pheroid™ vesicle groups were achieved when artesunate was entrapped 24 hours after manufacturing of Pheroid™ vesicles. Mefloquine co-formulated in the oil phase of Pheroid™ vesicles and evaluated after a 48 hour incubation period decreased the IC50 concentration by 36%. Extending the incubation period to 72 hours increased the efficacy of the Pheroid™ vesicles and the IC50 concentration was significantly decreased by 51%. In contrast with the results obtained with artesunate, entrapment of mefloquine in Pheroid™ vesicles 24 hours after manufacturing decreased the IC50 concentration significantly by 66%.
The LC-MS/MS method was found to be sensitive, selective and accurate for the determination of artesunate and its active metabolite, dihydroartemisinin (DHA) in mouse plasma and mefloquine in mouse whole blood. Most of the artesunate plasma concentrations were below the limit of quantification in the reference group and relatively high outliers were observed in some of the samples. The mean artesunate levels of the Pheroid™ vesicle group were lower compared to the reference group, but the variation within the Pheroid™ vesicle group lessened significantly. The mean DHA concentrations of the Pheroid™ vesicle group were significantly higher. DHA obtained a higher peak plasma drug concentration with the Pheroid™ vesicle group (173.0 ng/ml) in relation to the reference group (105.0 ng/ml) and at a much faster time (10 minutes in Pheroid™ vesicles in contrast to 30 minutes of the reference group). Pharmacokinetic models could not be constructed due to blood sampling per animal limitation. The incorporation of mefloquine in Pheroid™ vesicles did not seem to have improved results in relation to the reference group. No statistical significant differences were observed in the pharmacokinetic parameters between the two groups. The relative bioavailability (%) of the Pheroid™ vesicle incorporated mefloquine was 7% less bioavailable than the reference group.Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.
4
Kebwe, Stanislaus Kemero. "Pharmacokinetics of pyrimethamine and sulphadoxine in African children and adults." Thesis, University of Bradford, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.235765.
Full text
5
Clarke, Janet Barbara. "Immunogenicity and antigenicity of amodiaquine." Thesis, University of Liverpool, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.316558.
Full text
6
Huijben, Silvie. "Experimental studies on the ecology and evolution of drug-resistant malaria parasites." Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/3945.
Full textAbstract:
Drug resistance is a serious problem in health care in general, and in malaria treatment in particular, rendering many of our previously considered ‘wonder drugs’ useless. Recently, large sums of money have been allocated for the continuous development of new drugs to replace the failing ones. We seem to be one step behind the evolution of antimalarial resistance; is it possible to get one step ahead? Are interventions which slow down the evolution and spread of drug-resistant malaria parasites achievable? In this thesis, I address these issues with experimental data, using the well-established rodent malaria model Plasmodium chabaudi to understand the selective advantages and disadvantages drug-resistant parasites endure within a vertebrate host and the selective pressures various drug treatment regimes exert on these parasites. Competitive interactions between drug-resistant and drug-sensitive parasites were observed within the host, with resistant parasites having a competitive disadvantage in the absence of drug treatment. The frequency of resistant parasites at the start of the infection was an important determinant of the strength of selection: the lower their frequency, the stronger the competitive suppression in non-treated hosts and the greater their competitive release following drug treatment. Genetically similar genotypes, one resistant and one sensitive, showed similar dynamics following drug treatment. Multiplicity of infection did not have an effect on the within-host dynamics: a larger number of co-infecting susceptible genotypes did not lead to greater competitive suppression or release of resistant parasites. Lastly, various drug treatment regimes were compared. Conventional drug treatment resulted in the greatest selective advantage for drug-resistant parasites, while less aggressive treatments were equally as effective, or even better, at improving host health and reducing overall infectiousness. These studies demonstrate that altering the within-host ecology of drug-resistant parasites by administering drugs and hence removing the drug-sensitive competitors has a large influence on the transmission potential of drug-resistant parasites. Furthermore, this thesis provides proof of principle that other drug treatment regimes different from those currently in use could better control drug-resistant parasites, without compromising other treatment goals. In the case of malaria, less drugs may mean extending the useful lifespan of that drug.
7
Kaur, Gurminder. "A medicinal chemistry approach to drug repositioning in the treatment of tuberculosis and malaria." Doctoral thesis, University of Cape Town, 2016. http://hdl.handle.net/11427/23462.
Full textAbstract:
Tuberculosis (TB) and malaria continue to be major public health concerns, globally claiming 2-3 million deaths every year. A number of efficacious drugs are available for the treatment of TB and malaria, which, through various combination therapies, are fully effective in treating these diseases. However, the wide spread resistance in M. tuberculosis (Mtb) and P. falciparum, the causative agents of TB and malaria, respectively, has made the existing therapies less effective. Thus novel agents able to circumvent drug resistance and other challenges associated with existing TB and malaria treatments are urgently needed. The development of a new drug is a lengthy and costly process; therefore, approaches that can save both time and money need to be emphasised. Drug repositioning is one such approach that has been applied in this project. Drug repositioning basically involves a situation where a drug active in one disease is derivatised or used as a template for the synthesis of derivatives active in another disease. This approach has the potential to significantly shorten the drug discovery process. This study focused on the repositioning of two drugs, the antibacterial agent fusidic acid and the antipsychotic agent metergoline, in TB and/or malaria via medicinal chemistry approaches. New semisynthetic derivatives of fusidic acid and metergoline were synthesized and evaluated for antimycobacterial activity against the H37Rv strain of Mtb and antiplasmodial activity against the NF54 strain of P. falciparum.
8
Obua, Celestino. "Fixed-dose chloroquine and sulfadoxine/pyrimethamine treatment of malaria : outcome and pharmacokinetic aspects /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-144-9/.
Full text
9
Tagbor, Harry Kwami. "A randomised controlled trial of three drug regimes for the treatment of malaria in pregnancy in Ghana." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2005. http://researchonline.lshtm.ac.uk/4646524/.
Full textAbstract:
A thesis presented on a clinical trial of amodiaquine (AQ) and sulphadoxine-pyrimethamine (SP) used singly and in combination (AQ+SP) compared with chloroquine (CQ) for the treatment of 900 pregnant women who had falciparum malaria infection detected by a screening programme using OptiMAL antigen dipsticks during routine antenatal clinic sessions at the St. Theresa's hospital. Enrolment into the study began in March 2003 and ended in September 2004 but follow up of treated women continued to March 2005.
10
Cairns, Matthew. "Intermittent preventive treatment for malaria in infants and children protective mechanism drug choice and optimal dosing strategies." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.536869.
Full textBooks on the topic "Malaria drug treatment][Mefloquine"
1
World Health Organization (WHO). Guidelines for the treatment of malaria. 2nd ed. Geneva: World Health Organization, 2010.
Find full text
2
Staines, Henry M. Treatment and Prevention of Malaria: Antimalarial Drug Chemistry, Action and Use. Basel: Springer Basel, 2012.
Find full text
3
Microbiology, American Society for, ed. Magic bullets to conquer malaria: From quinine to qinghaosu. Washington, DC: ASM Press, 2010.
Find full text
4
Honigsbaum, Mark. The fever trail: In search of the cure for malaria. New York: Farrar, Straus and Giroux, 2002.
Find full text
6
Csizmadia, Emanuel. Antimalarial drugs: Costs, safety and efficacy. New York: Nova Biomedical Books, 2009.
Find full text
8
Kendrekar, Pravin. Drug Development for Malaria: Novel Approaches for Prevention and Treatment. Wiley & Sons, Limited, John, 2021.
Find full text
9
Treatment And Prevention Of Malaria Antimalarial Drug Chemistry Action And Use. Springer, 2012.
Find full textBook chapters on the topic "Malaria drug treatment][Mefloquine"
1
Nosten, Francois, Penelope A. Phillips-Howard, and Feiko O. ter Kuile. "Other 4-Methanolquinolines, Amyl Alcohols and Phentathrenes: Mefloquine, Lumefantrine and Halofantrine." In Treatment and Prevention of Malaria, 95–111. Basel: Springer Basel, 2011. http://dx.doi.org/10.1007/978-3-0346-0480-2_5.
Full text
2
Cheah, Phaik Yeong, Michael Parker, and Nicholas P. J. Day. "Ethics and Antimalarial Drug Resistance." In Ethics and Drug Resistance: Collective Responsibility for Global Public Health, 55–73. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-27874-8_4.
Full textAbstract:
Abstract There has been impressive progress in malaria control and treatment over the past two decades. One of the most important factors in the decline of malaria-related mortality has been the development and deployment of highly effective treatment in the form of artemisinin-based combination therapies (ACTs). However, recent reports suggest that these gains stand the risk of being reversed due to the emergence of ACT resistance in the Greater Mekong Subregion and the threat of this resistance spreading to Africa, where the majority of the world’s malaria cases occur, with catastrophic consequences. This chapter provides an overview of strategies proposed by malaria experts to tackle artemisinin-resistant malaria, and some of the most important practical ethical issues presented by each of these interventions. The proposed strategies include mass antimalarial drug administrations in selected populations, and mandatory screening of possibly infected individuals prior to entering an area free of artemisinin-resistant malaria. We discuss ethical issues such as tensions between the wishes of individuals versus the broader goal of malaria elimination, and the risks of harm to interventional populations, and conclude by proposing a set of recommendations.
3
Nzila, Alexis, and Kelly Chibale. "Anticancer Drug Repositioning Against Tropical Diseases: The Example of Methotrexate in the Treatment of Malaria." In Drug Discovery in Africa, 293–300. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-642-28175-4_12.
Full text
4
Teboh-Ewungkem, Miranda I., Olivia Prosper, Katharine Gurski, Carrie A. Manore, Angela Peace, and Zhilan Feng. "Intermittent Preventive Treatment (IPT) and the Spread of Drug Resistant Malaria." In The IMA Volumes in Mathematics and its Applications, 197–233. New York, NY: Springer New York, 2015. http://dx.doi.org/10.1007/978-1-4939-2782-1_9.
Full text
5
Magon, Pushpendra. "Drug Treatment of Malaria." In Pearls in Clinical Pediatrics, 269. Jaypee Brothers Medical Publishers (P) Ltd., 2013. http://dx.doi.org/10.5005/jp/books/11746_43.
Full text
6
Kofi Turkson, Bernard, Alfred Ofori Agyemang, Desmond Nkrumah, Reinhard Isaac Nketia, Michael Frimpong Baidoo, and Merlin Lincoln Kwao Mensah. "Treatment of Malaria Infection and Drug Resistance." In Plasmodium Species and Drug Resistance [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.98373.
Full textAbstract:
Malaria is a public health challenge that requires prompt treatment for those infected to make a full recovery. Treatment of malaria infection is to be started as soon as a diagnosis is confirmed. Antimalarial medications are administered to prevent and also to treat malaria. The type of medication used and the duration of therapy is dependent on the type of malaria-causing plasmodium species, the severity of the symptoms, geographical area where malaria infection occurred and the medication used to prevent malaria and whether there is pregnancy. Treatment of malaria from public health perspective is to reduce transmission of the infection to others, by reducing the infectious reservoir and to prevent the emergence and spread of resistance to antimalarial medicines. Medications used in the treatment of malaria infection come from the following five groups of chemical compounds: quinolines and aryl amino alcohols, antifolate, artemisinin derivatives, hydroxynaphthoquinones and antibacterial agents. The treatment of malaria is not initiated until the diagnosis has been established through laboratory testing. Artemisinin-based Combination Therapy (ACTs) has been used for the treatment of uncomplicated malaria. ACTs are also to enhance treatment and protect against the development of drug resistance. IV artesunate is used in the treatment of severe malaria, regardless of infecting species.
7
Berry, Colin. "Proteases as Drug Targets for the Treatment of Malaria." In Proteases of Infectious Agents, 165–88. Elsevier, 1999. http://dx.doi.org/10.1016/b978-012420510-9/50033-8.
Full text
8
Swai, Hulda, Boitumelo Semete, Lonji Kalombo, and Paul Chelule. "Nanotechnology in Drug Delivery for Malaria and Tuberculosis Treatment." In Bionanotechnology. CRC Press, 2008. http://dx.doi.org/10.1201/9781420007732.ch16.
Full text
9
Lunev, Sergey, Fernando A. Batista, Soraya S. Bosch, Carsten Wrenger, and Matthew R. Groves. "Identification and Validation of Novel Drug Targets for the Treatment of Plasmodium falciparum Malaria: New Insights." In Current Topics in Malaria. InTech, 2016. http://dx.doi.org/10.5772/65659.
Full text
10
Tsegaye Tseha, Sintayehu. "Plasmodium Species and Drug Resistance." In Plasmodium Species and Drug Resistance [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.98344.
Full textAbstract:
Malaria is a leading public health problem in tropical and subtropical countries of the world. In 2019, there were an estimated 229 million malaria cases and 409, 000 deaths due malaria in the world. The objective of this chapter is to discuss about the different Plasmodium parasites that cause human malaria. In addition, the chapter discusses about antimalarial drugs resistance. Human malaria is caused by five Plasmodium species, namely P. falciparum, P. malariae, P. vivax, P. ovale and P. knowlesi. In addition to these parasites, malaria in humans may also arise from zoonotic malaria parasites, which includes P. inui and P. cynomolgi. The plasmodium life cycle involves vertebrate host and a mosquito vector. The malaria parasites differ in their epidemiology, virulence and drug resistance pattern. P. falciparum is the deadliest malaria parasite that causes human malaria. P. falciparum accounted for nearly all malarial deaths in 2018. One of the major challenges to control malaria is the emergence and spread of antimalarial drug-resistant Plasmodium parasites. The P. vivax and P. falciparum have already developed resistance against convectional antimalarial drugs such as chloroquine, sulfadoxine-pyrimethamine, and atovaquone. Chloroquine-resistance is connected with mutations in pfcr. Resistance to Sulfadoxine and pyrimethamine is associated with multiple mutations in pfdhps and pfdhfr genes. In response to the evolution of drug resistance Plasmodium parasites, artemisinin-based combination therapies (ACTs) have been used for the treatment of uncomplicated falciparum malaria since the beginning of 21th century. However, artemisinin resistant P. falciparum strains have been recently observed in different parts of the world, which indicates the possibility of the spread of artemisinin resistance to all over the world. Therefore, novel antimalarial drugs have to be searched so as to replace the ACTs if Plasmodium parasites develop resistance to ACTs in the future.